Antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis associated with rheumatoid arthritis: An unusual case report

Clinically relevant renal lesions in rheumatoid arthritis (RA) are not common. More often renal involvement is related to complications of therapy than the disease itself. The most common forms of primary renal disease in RA are membranous glomerulonephropathy and a pure mesangial proliferative glomerulonephritis. Some studies have described the association between crescentic glomerulonephritis (crescentic GN) and RA, but they were all found to be perinuclear antineutrophil cytoplasmic antibody (p-ANCA) positive. However, RA associated with ANCA negative pauci-immue crescentic GN has not been reported. This is a case report of a 37-year-old female with RA who initially presented with general oedema and acute deterioration of renal function. The renal biopsy revealed ANCA negative pauci-immune crescentic GN. The patient was treated with steroid pulse and plasmapheresis, but not cyclophosphamide because of severe urosepsis. Despite the use of aggressive therapy, her renal function was not improved and she underwent maintenance haemodialysis thereafter. Because ANCA negative crescentic GN may occur in RA patients without frank systemic vasculitis, but with severe clinical manifestation, a heightened suspicion for a relatively 'silent' crescentic GN would have led to the correct diagnosis and appropriate treatment.     

Long-term results of transpedicle body augmenter in treating burst fractures

Background:

Short-segment fixation alone to treat thoracolumbar burst fractures is common but it has a 20-50% incidence of implant failure and rekyphosis. A transpedicle body augmenter (TpBA) to reinforce the vertebral body via posterior approach has been reported to prevent implant failure and increase the clinical success rate in treating burst fracture. This article is to evaluate the longterm results of short-segment fixation with TpBA for treatment of thoracolumbar burst fractures.

Materials and Methods:

Patients included in the study had a single-level burst fracture involving T11-L2 and no distraction or rotation element with limited neurological deficit. Patients in the control group (n = 42) were treated with short-segment posterior instrumentation alone, whereas patients in the augmented group (n = 90) were treated with a titanium spacer designed for transpedicle body reconstruction. The followup was 48-101 months. The radiographic and clinical results were evaluated and compared by Student''s t test and Fisher''s exact test.

Results:

The blood loss, operation time and hospitalization were similar in both the groups. The immediate postoperative anterior vertebral restoration rate of the augmented group was similar to that of the control group (97.6% ± 2.4% vs. 96.6% ± 3.2%). The final anterior vertebral restoration was greater in the augmented group than in the control group (93.3% ± 3.4% vs. 62.5% ± 11.2%). Immediate postoperative kyphotic angles were not significantly different between the groups (3.0° ± 1.8° vs. 5.1° ± 2.3°). The final kyphotic angles were less in the augmented group than the control group (7.3° ± 3.5° vs. 20.1° ± 5.4°). The augmented group had less (P < 0.001) implant failure [0% (n=0) vs. 23.8% (n=10)] for the control group) and more patients (P < 0.001) with no pain or minimal or occasional pain (Grade P1 or P2) than the control group [90.0% (n=81) vs. 66.7% (n=28)]. All patients in the augmented group and 39 (92.8%) patients in the control group experienced neurological recovery to Frankel Grade E. Three patients in the control group had improvement to Frankel Grade D from Frankel Grade C, but later had deterioration to Frankel Grade C because of loosening and dislodgement of the implant.

Conclusion:

Posterior body reconstruction with TpBA can maintain kyphosis correction and vertebral restoration, prevent implant failure and lead to better clinical results.     

Activators of soluble guanylate cyclase for the treatment of male erectile dysfunction

Soluble guanylate cyclase (sGC) is an important enzyme in corpus cavernosum smooth muscle cells as it is one of the regulators of the synthesis of cGMP. The efficacy of sildenafil (Viagra) in the treatment of male erectile dysfunction indicates the importance of the cGMP system in the erectile response as the increased levels of cGMP induce relaxation of the corpus cavernosum. sGC is physiologically activated by nitric oxide (NO) during sexual stimulation, and its activity can be pharmacologically enhanced by several NO-donors. Agents like YC-1 can also activate sGC after binding to a novel allosteric site in the enzyme, a site different from the NO binding site. YC-1 can relax rabbit cavernosal tissue and it facilitates penile erection in vivo. This review summarizes the enzymology, biochemistry and pharmacology of this novel allosteric site and its relevance for the regulation of penile function. This type of sGC activators represent a new class of compounds with a different pharmacological profile in comparison to the classical NO-donors and they could be beneficial for the treatment of male erectile dysfunction.     

The experience of biliary tract complications after liver transplantation

AIM: To report the morbidity and mortality of patients who undergo liver transplantation with or without T-tube implantation after choledochocholedochostomy as well as to discuss management of biliary complications. PATIENTS AND METHODS: We performed a retrospective review of 104 liver transplantations from August 2001 to February 2006, including 51 patients who underwent choledochocholedochostomy with a T-tube (group A) and 53, without a T-tube (group B). We compared the clinical characteristics, operative methods, biliary complications, morbidity, mortality, and management of complications. RESULTS: Between the two groups, there were no significant differences in clinical characteristics, including sex, age, and indication for liver transplantation (hepatitis B virus, hepatitis C virus, alcoholic liver cirrhosis, or hepatocellular carcinoma), Child-Pugh classification, Model for End-stage Liver Disease score, and operative macroscopic/microscopic findings. Additionally, there was no significant difference in biliary complications. Among these 104 patients, 14 (13.5%) developed biliary complications: seven anastomotic strictures, two intrahepatic duct strictures, two anastomotic stricture combined intrahepatic duct stricture, one bile leakage, one bile leakage combined with anastomotic stricture, and one external biliary compression. Nine patients with anastomotic stricture underwent endoscopy with a stent, which was successful only in two patients. The other six patients underwent choledochojejunostomy with excellent results. CONCLUSIONS: This study showed choledochocholedochostomy with or without a T-tube after liver transplantation did not influence the biliary complications. The biliary complications of anastomotic stricture after liver transplantation can be managed by endoscopy with a stent. If endoscopy fails, surgical intervention should be considered immediately.     

Telomerase Activity in Tumor and Remnant Liver as Predictor of Recurrence and Survival in Hepatocellular Carcinoma after Resection

Background and Aim Results after curative liver resection in hepatocellular carcinoma are unsatisfactory with regard to high postoperative intrahepatic recurrence and liver failure. This study evaluates telomerase activity in liver with and without tumor as a predictor of recurrence and survival. Materials and Methods Liver tissue with and without tumor from 53 hepatocellular carcinoma patients receiving curative resection during the period of 1998–2000 was used for detecting telomerase activity by PCR-ELISA. Clinicopathological data were compared to identify predictors of recurrence and survival. Results Telomerase activity was detected in 98% of liver tissue with tumor and 70% liver tissue without. Telomerase activity in cancerous liver correlated significantly with HCV infection (P = 0.012) and cirrhotic change in liver parenchyma (P = 0.006). Telomerase activity in non-cancerous liver correlated with high serum AFP level (P = 0.002). The telomerase activity of liver tissue with and without tumor is significant higher in patients with recurrence than in those without recurrence, 413.7 ± 100.5 versus 110.8 ± 32.7, P = 0.006, and 34.7 ± 14.2 versus 4.2 ± 1.4, P = 0.039. Recurrence could be predicted by abnormally high tumor telomerase activity (P = 0.026) or by advanced TNM stage (P = 0.001). TNM stage or high serum ALT level could predict multinodular intrahepatic recurrence (P = 0.028 and P = 0.030). High serum AFP combined with high telomerase activity in liver without tumor had a significant ability to predict poor survival (OR: 11.19, CI: 1.95–64.12, P = 0.007). Conclusion Tumor telomerase is an independent predictor of recurrence. Simultaneous high remnant liver telomerase and high serum AFP is a strong negative predictor of survival.     

SUMO4 M55V variant is associated with diabetic nephropathy in type 2 diabetes

OBJECTIVE-SUMO4 mRNA was recently found to be mainly expressed in the kidney, and the methionine-to-valine substitution at codon 55 (M55V) variant of SUMO4 may induce higher nuclear factor-kappaB (NF-kappaB) activity. Because NF-kappaB is known to mediate the development of diabetic nephropathy, we examined the association between the SUMO4 M55V variant and the severity of diabetic nephropathy. RESEARCH DESIGN AND METHODS-We recruited a total of 430 patients with type 2 diabetes. The M55V (rs237025, 163A-->G) polymorphism of SUMO4 was genotyped by real-time PCR, and urine albumin concentration was measured by radioimmunoassay. RESULTS-The frequencies of SUMO4 AA, GA, and GG were 52.6, 40.7, and 6.7%, respectively, in the normoalbuminuric group; 45.5, 47.3, and 7.1% in the microalbuminuric group; and 36.9, 46.2, and 16.9% in the macroalbuminuric group. We detected a significant linear trend for SUMO4 genotype between the macroalbuminuric and normoalbuminuric groups. The mean urine albumin-to-creatinine ratio (42.3 +/- 108.82 mg/mmol) in the GG group was significantly higher than in the AA (14.9 +/- 51.49 mg/mmol) and GA (17.0 +/- 43.74 mg/mmol) groups. Multivariate logistic regression analysis showed the SUMO4 M55V variant to be independently associated with the severity of diabetic nephropathy. CONCLUSIONS-This study indicates that the SUMO4 gene M55V variant is associated with severity of diabetic nephropathy in patients with type 2 diabetes.     

Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee in rats: role of excitatory amino acids

OBJECTIVE: Our present study examined the effect of intra-articular cyclooxygenase-2 (COX-2) inhibitor parecoxib on osteoarthritis (OA) progression and the concomitant changes in excitatory amino acids' (EAAs) levels of the anterior cruciate ligament-transected (ACLT) knee joint dialysates. METHODS: OA was induced in Wistar rats by anterior cruciate ligament transection of the knee of one hindlimb, the other was left unoperated and untreated. Rats were placed into four groups: Group ACLT/P received intra-articular parecoxib injection (100 microg) in the ACLT knee once a week for 5 consecutive weeks starting at 8 weeks after surgery. Group ACLT/S received the same procedure as group ACLT/P with saline injection instead. Na?ve (Na?ve/P) rats received only intra-articular parecoxib injection in one knee once a week for 5 consecutive weeks without surgery. The sham-operated rats underwent arthrotomy only without treatment. Twenty weeks after surgery, knee joint dialysates were collected and EAAs' concentration was assayed by high-performance liquid chromatography, and gross morphology and histopathology (Mankin and synovitis grading) were examined on the medial femoral condyles and synovia. RESULTS: Parecoxib alone had no effect on cartilage and synovium of normal knees in Na?ve/P rats. In ACLT/P rats, parecoxib treatment showed a significant inhibition of cartilage degeneration of the medial femoral condyle at both the macroscopic level (1.15+/-0.17 vs 2.55+/-0.12, P<0.05) and the Mankin scores (3.03+/-0.28 vs 8.82+/-0.43, P<0.05). Intra-articular parecoxib injection also suppressed the synovial inflammation of ACLT joint compared to the ACLT/S group (3.92+/-0.41 vs 9.25+/-0.32, P<0.05). Moreover, glutamate and aspartate levels were also significantly reduced in the ACLT/P group compared to the ACLT/S group by parecoxib treatment (91.2+/-9.4% vs 189.5+/-17.0%, P<0.05 and 98.2+/-11.6% vs 175.3+/-12.4%, P<0.05, respectively). CONCLUSION: This study shows that intra-articular injection of COX-2 inhibitor parecoxib inhibits the ACLT-induced OA progression; it was accompanied by a reduction of glutamate and aspartate concentration in the ACLT joint dialysates. From our present results, we suggested that intra-articular parecoxib injection, in addition to the anti-inflammatory effect, inhibiting the EAAs' release, may also play a role in inhibiting the traumatic knee injury induced OA progression.     

Another option to treat Kümmell’s disease with cord compression

The efficiency of short-segment fixation with transpedicle body augmenter (a titanium spacer with bone-ingrowth porous surface, TpBA) to treat Kümmell's disease with cord compression (stage III) was retrospectively evaluated. No laminectomy or instrumentation reduction was done. Inclusion criteria included Frankel CDE, single-level within T10-L2. FU rate was 88%, i.e. 21 cases were included. Frankel function classification was 6E9D6C. Mean age was 72+/-8 years. F:M was 16:5. FU period was 48 M (range, 30-76 M). The hospitalization was 4.5+/-2.2 days; operation time, 70.4+/-17.2 min; blood loss, 150+/-72 cc. Final Frankel class was 20E1D. Complications included two superficial infection and one pneumonia. Body height and kyphosis were all corrected significantly and well preserved at the final visit. No TpBA dislodgement or implant failure was noted; however, three cases developed new compression fractures. The clinical outcome showed 81% with P1 or P2 by Denis pain scale. This method can decompress spinal canal, maintain kyphosis correction and vertebral restoration, prevent implant failure, and attain good clinical results.     

Liver transplantation is an alternative treatment of hepatocellular carcinoma beyond the Milan criteria

Background

The decision to perform liver transplantation (LT) or liver resection (LR) for patients with hepatocellular carcinoma (HCC) who are beyond the Milan criteria remains controversial.

Methods

We retrospectively analyzed outcome data for 179 patients with HCC beyond the Milan criteria who were treated with LR (n = 135) or LT (n = 44). Univariate and multivariate Cox proportional hazard models were established. Kaplan-Meier survival curves were generated, and a log-rank test was performed to compare group survival status.

Results

Patients who underwent LR group were significantly older, had a lower TNM stage, and were more likely to have unilateral disease and noncirrhotic liver. Significantly more patients in the LR group had recurrence (53.3% vs 29.5%) or died (61.5% vs 43.2%) than patients in the LT group. Recurrence-free survival rates were 11.9% for the LR group and 61.5% for the LT group. The median overall survival duration showed no statistically difference between the LR group (28.0 months) and the LT group (50.0 months).

Conclusions

LT may be the better choice for patients with HCC beyond the Milan criteria.