Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephropathy

Background

The primary abnormal manifestation in immunoglobulin A nephropathy (IgAN) is recurring bouts of hematuria with or without proteinuria. Although immunohistochemical analysis of renal biopsy tissue remains the gold standard not only for diagnosis but also for evaluating the activity of IgAN, new sensitive and reasonably specific noninvasive tests are emerging to guide therapeutic strategy applicable to all stages of IgAN. The present study examined serum levels of galactose-deficient IgA1 (Gd-IgA1) and its immune complex (IgA/IgG-IC) as noninvasive markers for the disease activity.

Methods

We enrolled 50 IgAN patients (male 40 %, median age 37 years) showing complete or partial clinical remission after steroid pulse therapy with tonsillectomy (TSP) whose clinical data and serum could be followed up for 3–5 years.

Results

Cross-sectional analysis revealed that the degree of hematuria and proteinuria were significantly associated with levels of Gd-IgA1 and levels of IgA/IgG-IC. Longitudinal analysis further showed that from the group of 44 patients with heavy hematuria before TSP, 31 patients showed complete disappearance of hematuria (group A), but the remaining patients did not (group B). Although the levels of Gd-IgA1 and IgA/IgG-IC in the two groups before TSP were similar, percentage decrease of Gd-IgA1 and IgA/IgG-IC levels in group A was significantly higher than in group B.

Conclusion

Disease activity of IgAN assessed by hematuria and proteinuria correlated with serum levels and changes of Gd-IgA1 and IgA/IgG-IC. These new noninvasive disease activity markers can be useful for future activity scoring system and guiding therapeutic approaches.     

Sentinel Node Navigation Surgery for Early Gastric Cancer: Analysis of Factors Which Affect Direction of Lymphatic Drainage

World Journal of Surgery - We started performing sentinel node navigation surgery (SNNS) for patients with early gastric cancer (EGC) using infrared ray electronic endoscopy (IREE) with indocyanine...     

Neonatal ovarian cysts: management with reference to magnetic resonance imaging

OBJECTIVE: Ultrasound (US) has been used as a tool to determine the indication for surgery for neonatal ovarian cysts. The purpose of this study was to investigate whether magnetic resonance imaging (MRI) contributes to optimal management. METHODS: Between 1993 and 2001, US and MRI studies were simultaneously performed on 13 consecutive infants younger than 2 months of age with ovarian cysts. The US Patterns were classified as complex or simple. Signal intensity (SI) of the cysts on MRI was compared with that of the liver on T1-weighted images (T1WI) and with urine on T2-weighted images (T2WI). We assumed that high SI on T1WI and iso or low SI on T2WI indicated complications. RESULTS: There were 10 complex and three simple cysts on US. Of the 10 complex cysts, two had no complications at surgery or resolved spontaneously. These two cysts showed low SI on T1WI. Eight complex cysts showed high SI on T1WI and all were haemorrhagic. The US diagnosis corresponded to the MRI findings in three simple cysts. The sensitivity of US for haemorrhage was 80%, and that of MRI was 100%. CONCLUSIONS: We found that MRI was a more reliable diagnostic modality than US for diagnosing neonatal ovarian cysts.     

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.     

Excellent Long-term Outcome of ABO-Incompatible Living Donor Kidney Transplantation in Japan

Owing to the severe shortage of cadaveric grafts in Japan, we have performed ABO-incompatible living donor kidney transplantation since 1989. This study assessed short- and long-term outcomes in 441 patients who received ABO-incompatible living donor kidney transplants between January 1989 and December 2001. We compared our results with historical data from 1055 recipients of living kidney transplantation. Overall patient survival rates 1, 3, 5, 7, and 9 years after ABO-incompatible transplantation were 93%, 89%, 87%, 85%, and 84%, respectively. Corresponding overall graft survival rates were 84%, 80%, 71%, 65%, and 59%. After ABO-incompatible transplantation, graft survival rates were significantly higher in patients 29 years or younger than in those 30 years or older and in patients who received anticoagulation therapy than in those who did not receive such therapy. There were no significant differences between A-incompatible and B-incompatible recipients with respect to clinical outcomes. The graft survival rate at 1 year in the historical controls was slightly but not significantly higher than that in our recipients of ABO-incompatible transplants. We conclude that long-term outcome in recipients of ABO-incompatible living kidneys is excellent. Transplantation of ABO-incompatible kidneys from living donors is a radical, but effective treatment for end-stage renal disease.     

A nonerythropoietic derivative of erythropoietin inhibits tubulointerstitial fibrosis in remnant kidney

Background

The tissue-protective effects of erythropoietin (EPO) have been extensively investigated, and EPO administration can raise the hemoglobin (Hb) concentration. Recently, we reported that carbamylated erythropoietin (CEPO) protected kidneys from ischemia-reperfusion injury as well as EPO.

Methods

To investigate the clinical applications of CEPO, we next evaluated the long-term therapeutic effect of CEPO using a tubulointerstitial model rat. We randomized remnant kidney model rats to receive saline, EPO, or CEPO for 8?weeks.

Results

CEPO- and EPO-treated rats had improved serum creatinine levels compared with saline-treated remnant kidney model rats, although the Hb level was significantly increased in EPO-treated rats. Two-photon microscopy revealed that EPO/CEPO significantly ameliorated tubular epithelial cell damage assessed by endocytosis. In addition, CEPO or EPO protected endothelial cells with a sustained blood flow rate. EPO or CEPO suppressed the number of TUNEL-positive apoptotic cells with weak ??SMA staining. Furthermore, PCR analysis demonstrated that TGF-?? and type I collagen expression was attenuated in EPO- or CEPO-treated rats, accompanied by a significant decrease in interstitial fibrosis.

Conclusion

We established a long-term therapeutic approach to protect tubulointerstitial injury with CEPO, and thus, the therapeutic value of this approach warrants further attention and preclinical studies.     

Skeletal Analysis of the Long Bone Abnormality (lbab/lbab) Mouse, A Novel Chondrodysplastic C-Type Natriuretic Peptide Mutant

Long bone abnormality (lbab/lbab) is a strain of dwarf mice. Recent studies revealed that the phenotype is caused by a spontaneous mutation in the Nppc gene, which encodes mouse C-type natriuretic peptide (CNP). In this study, we analyzed the chondrodysplastic skeletal phenotype of lbab/lbab mice. At birth, lbab/lbab mice are only slightly shorter than their wild-type littermates. Nevertheless, lbab/lbab mice do not undergo a growth spurt, and their final body and bone lengths are only ~60% of those of wild-type mice. Histological analysis revealed that the growth plate in lbab/lbab mice, especially the hypertrophic chondrocyte layer, was significantly thinner than in wild-type mice. Overexpression of CNP in the cartilage of lbab/lbab mice restored their thinned growth plate, followed by the complete rescue of their impaired endochondral bone growth. Furthermore, the bone volume in lbab/lbab mouse was severely decreased and was recovered by CNP overexpression. On the other hand, the thickness of the growth plate of lbab/+ mice was not different from that of wild-type mice; accordingly, impaired endochondral bone growth was not observed in lbab/+ mice. In organ culture experiments, tibial explants from fetal lbab/lbab mice were significantly shorter than those from lbab/+ mice and elongated by addition of 10⁻⁷ M CNP to the same extent as lbab/+ tibiae treated with the same dose of CNP. These results demonstrate that lbab/lbab is a novel mouse model of chondrodysplasia caused by insufficient CNP action on endochondral ossification.     

A screening model for low bone mass in elderly Japanese men using quantitative ultrasound measurements: Fujiwara-Kyo Study

Screening for low bone mass is important to prevent fragility fractures in men as well as women, although men show a much lower prevalence of osteoporosis than women. The purpose of this study was to establish a screening model for low bone mineral density (BMD) using a quantitative ultrasound parameter and easily obtained objective indices for elderly Japanese men. We examined 1633 men (65-84 yr old) who were subjects of the Fujiwara-Kyo Study. Speed of sound (SOS) at the calcaneus was determined, and BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine (LS), total hip (TH), and femoral neck (FN). Low BMD was defined as >1 standard deviation below the young adult mean, in accordance with World Health Organization criteria. We performed receiver operating characteristic (ROC) analysis to identify a better screening model incorporating SOS and determined the optimal cutoff value using Youden index. Prevalences of low BMD at the 3 skeletal sites were 27.8% (LS), 33.5% (TH), 48.6% (FN), and 43.3% at either LS or TH. The greatest area under the ROC curve (0.806, 95% confidence interval: 0.785-0.828) and smallest Akaike's information criterion were obtained in the multivariate model incorporating SOS, age, height, and weight for predicting low BMD at all skeletal sites. This model predicted low BMD at TH with the sensitivity of 0.726 and specificity of 0.739, whereas a similar model predicted low BMD at LS with much lower validity. We conclude that the multivariate model for TH could be used to screen for low BMD in elderly Japanese men.     

Tissue factor antisense oligonucleotides prevent renal ischemia-reperfusion injury

BACKGROUND: Tissue factor (TF) expression is induced on macrophages and endothelial cells during the immune response. We designed an antisense (AS) phosphorothioate oligodeoxynucleotide (ODN) to specifically inhibit the expression of rat TF to study the effects of the AS ODN on renal ischemia-reperfusion injury in the rat. METHOD: AS-1 ODN for TF was delivered intravenously to inhibit the expression of TF in endothelial cells. After 8 hr, the right kidney was harvested and the left renal artery and vein were clamped. The kidney was reperfused after 90 min of ischemia, and rats were killed at 0, 1.5, 5, 12, and 24 hr after reperfusion. TF expression was analyzed by immunohistochemical staining using monoclonal antibody. RESULTS: In the untreated ischemic group, 0 of 20 rats survived beyond day 3. However, treatment with AS-1/TF led to 12 of 20 rats surviving beyond day 4. TF was detected on distal tubular epithelial cells, endothelial cells, and blood vessels but not on necrotic and proximal tubular epithelial cells. The necrotic area extended and encompassed nearly all of the ischemic kidney within 12 hr after reperfusion. The necrotic area and the grade of TF staining were more significantly reduced in the AS-1/TF-treated group than in the control group. Furthermore, fluorescein isothiocyanate-labeled AS-1/TF was significantly intense in tubular epithelial cells 8 hr after intravenous administration. CONCLUSIONS: The results indicate that AS-1/TF inhibited the ischemia-reperfusion injury of the kidney. Microcirculatory incompetence resulting from microthrombus may cause the formation and development of necrosis.     

Laparoscopy-assisted Billroth-I gastrectomy (LADG) for cancer: our 10 years' experience

To evaluate laparoscopy-assisted Billroth-I gastrectomy (LADG), we examined the outcome of its use over the last 10 years. From December 1991 to December 2001, 116 patients with early gastric cancer underwent LADG in the surgical department of Oita Medical University and Koga hospital by the same surgical staffs. An operation record and clinical sheets were reviewed to obtain the operative findings, clinical course, and pathologic findings of resected specimens to evaluate the usefulness of LADG in the management of early gastric cancer. In all LADG procedures, regional lymph nodes dissection (D1+alpha) was successfully performed using laparoscopy. The mean operative duration and blood loss were 234 minutes and 139 mL, respectively. There were only four major complications, including pneumonia, leakage of anastomosis, pancreatic injury, and anastomotic stenosis, but all these cases were successfully treated conservatively. The mean length of postoperative stay was 16.3 +/- 2.5 days. All patients except one, who died not of cancer but of cerebral bleeding, were alive without recurrence or port-site metastasis during mean follow-up period of 45 months. We successfully performed 116 LADG procedures over 10 years. This procedure is recommended for the treatment of patients with early gastric cancer because of the associated good prognosis and several benefits, including less invasiveness and early recovery.