Benefit of Neoral C2 monitoring in de novo cardiac transplant recipients receiving basiliximab induction

BACKGROUND: For cyclosporine (CsA), 2-hr postdose level (C2) is the best single time point predictor of the area under the curve and a critical measure for effective dosing. The therapeutic CsA microemulsion (Neoral) C2 range in de novo heart transplant patients remains to be determined. PURPOSE: The purpose of this study was to determine the efficacy of CsA C2 monitoring in de novo heart transplant patients receiving basiliximab induction. METHODS: This prospective, multicenter, randomized study enrolled 87 adult heart transplant recipients stratified according to 4 to 6 hrs posttransplant serum creatinine less than or equal to 170 micromol/L (cohort A) or more than 170 micromol/L (cohort B). Patients in cohort A were randomized into three C2 ranges (A1: "high" n=25, 1600-1800 ng/mL; A2: "intermediate" n=27, 1400-1600 ng/mL; and A3: "low" n=24, 1200-1400 ng/mL). Patients in cohort B were randomized into intermediate (n=5) and low C2 (n=6). Target ranges were progressively lowered after 1 month. Immunosuppression included basiliximab, Neoral, mycophenolate mofetil, and corticosteroids. Endpoints were acute rejection and renal function. RESULTS: The incidence of acute rejection at 12 months was 44% in group A1, 41% in group A2, 33% in group A3, and 27% in cohort B. Pretransplant and 12-month creatinine clearance (mL/min) were group A1, 72+/-25 and 64+/-24; group A2, 81+/-32 and 68+/-25; group A3, 91+/-28 and 86+/-26; and cohort B, 62+/-28 and 79+/-37. CONCLUSION: These results suggest that C2 monitoring is safe in de novo heart transplant patients. A low Neoral C2 range in combination with basiliximab induction resulted in preserved renal function without increased risk of acute rejection.     

A new biodegradable braided self-expandable PLGA prostatic stent: an experimental study in the rabbit

PURPOSE: The biodegradable PLGA (a copolymer of L-lactide and glycolide) urethral stent with a spiral configuration has been used clinically for the prevention of postoperative urinary retention after different types of thermal therapy for benign prostatic hyperplasia. A new braiding pattern for this stent has recently been developed by our group. The aim here was to investigate the in situ degradation and biocompatibility of the new braided stent in the rabbit urethra. MATERIALS AND METHODS: PLGA stents with a one-over-one braiding pattern and steel stents served as controls that were inserted into the posterior urethras of 24 male rabbits using a special delivery instrument. The animals were sacrificed after 1 week, 1 month, 2 months, or 4 months, and light microscopy and histologic analyses were performed. RESULTS: The delivery instrument worked well and cystoscopy was not needed in the insertion process. The braided PLGA stents degraded smoothly in 1 to 2 months. The metallic stents induced more epithelial hyperplasia and epithelial changes than the biodegradable stents at all time points analyzed. These differences increased during follow-up. CONCLUSION: The degradation process was well controlled and the biodegradable stents were more biocompatible than the metallic stents. The new stent can be inserted into the posterior urethra without cystoscopic aid.     

Chronic active gastritis in X-linked lymphoproliferative disease

Gastric lesions in primary constitutive immune deficiencies include multifocal atrophic gastritis, erosive pangastritis, and a pattern of gastric lesions reminiscent of graft-versus-host disease. We describe the genetic anomalies in 2 monozygotic twins with an X-linked lymphoproliferative disease (XLP; MIM 308240), a rare familial setting of high susceptibility to Epstein-Barr virus (EBV). Since early childhood, both twin brothers exhibited a severe chronic active atrophic pangastritis. A germline screening of the SH2D1A (MIM 300490) and BIRC4 (MIM 300079) genes was performed, and also a high-resolution whole-genome SNP profiling (Infinium Sentrix Human-1 Genotyping BeadChip, Illumina). A 3 Megabase deletion in the Xq25 region, encompassing the SH2D1A gene, was defined by SNP array genotyping. Histologic analysis of yearly or twice yearly gastric biopsies in both children showed a Helicobacter pylori-negative, Epstein-Barr virus-negative chronic active atrophic pangastritis, with superficial ulcer formation, foveolar hyperplasia, glandular dilatation and ultimately pseudopyloric and intestinal metaplasia. No such chronic active inflammatory gastric lesions have been reported to date in XLP. The similarities between XLP and common variable immunodeficiency (MIM 240500) underscore the need for early recognition and close monitoring of these gastric lesions, with special regard to their neoplastic potential. No infectious cause was determined. We favor a dysimmune mechanism in the development of this chronic atrophic gastritis, presenting a striking similarity to the recently described atrophic autoimmune pangastritis.     

超滤法测定表面活性剂临界胶束浓度

对超滤法测定表面活性剂的临界胶束浓度(CMC)的单点式超滤法、超滤曲线法、双点式超滤法进行了研究,比较了理想与真实超滤曲线,对超滤膜用于超滤法测定CMC的适用性及容积效应进行了考察.初步探讨了用双点式超滤法代替作超滤曲线法测定CMC的可行性和准确性,并与单点式超滤法进行了比较.试验结果表明,用双点式超滤法测定CMC具有准确性较高、操作简便、节省时间和节约样品用量等优点.用双点法测得的SDS和SLAS的CMC分别为6.70mmol/L和1.40mmol/L;与超滤曲线法得到的CMC相比,偏差分别为2.9%和3.4%.     

Effect of various trophic factors on bacterial translocation in experimental short bowel syndrome

Massive bowel resection triggers an adaptive process in the remaining intestine in spite of which, bacterial translocation (BT) is frequent under these conditions. Several trophic factors, including growth hormone (GH), epidermal growth factor (EGF) and insuline (INS) are involved in the process of adaptation in short bowel syndrome (SBS). However, the effect of GH, EGF or INS on BT has not been investigated experimentally. The aim of the study was to test the hypothesis that GH, EGF or INS administration prevents BT in rats with SBS receiving only parenteral nutrition (PN). Thirty-seven adult Wistar rats underwent central venous cannulation and were randomly assigned to one of two groups receiving for ten days four treatment regimes: PN group (N = 10) fasting, all-in-one PN solution (300 mL/kg/24 h, 280 kcal/kg/24 h), 80% gut resection including ileo-cecal valve. GH group (N = 9) fasting, same PN regime and resection plus GH (1 mg/kg/d, s.c.). EGF group (N = 9): same PN regime and resection plus EGF (150 microgr/24 h, e.v.) INS group(N = 9): same PN regime and resection plus INS (1 U.I./100 g/24 h s.c.) At the end of the experiment the rats were exanguinated and mesenteric lymph nodes and samples of systemic and portal blood were obtained and cultured. Several samples of full-thickness jejunal wall were taken for measuring cell proliferation index (PCNA) and mucosal thickness. Jejunal mucosal thickness increased by 30%, 28% and 29% and PCNA index by 21%, 20% and 25% in GH, EGF and INS, treated rats respectively in comparison with those treated with PN alone. However, contrary to our expectations, BT expressed by positive culture of intestinal germs in systemic blood was demonstrated respectively in 44%, 40% and 28% of GH, EGF and INS animals, respectively, and in 0% of PN-only rats. Although exogenous GH, EGF or INS improves gut mucosal structure in rats with SBS treated with PN, it seems to increase rather than decrease mucosal permeability to intestinal germs in them.     

INCIDENCE,DISTRIBUTION AND MECHANISMS OF MICROSATELLITE INSTABILITY IN DIFFERENT COLORECTAL CANCER AGE GROUPS

The increase in the incidence of colorectal cancer (CRC) is higher for proximal than for distal tumors. As microsatellite instability (MSI) is a feature of proximal tumors, we hypothesize that an increase in MSI tumors may account for the age‐related proximal shift in CRC. Methods: A representative sample of 230 CRCs from 3 age groups was selected from a CRC database. MSI was determined by PCR. MLH1 and MSH2 expression was determined by immunohistochemistry, and the methylation of the MLH1 gene promotor (PM) by methylation‐specific PCR. Results: MSI tumors became more frequent (p < 0.01 chi square) and more proximal in distribution (p = 0.01 loglinear) in the oldest age group. MSI was associated with loss of expression of MSH2 in the young age group. PM and inactivation of MLH1 increased with age. Conclusion: MSI tumors became more frequent and proximal in older patients. This trend was associated with differences in the underlying mechanisms responsible for the MSI phenotype.     

Neglected patellar tendon rupture: a case of reconstruction without quadriceps lengthening

Neglected rupture of the patellar tendon is a rare, can be easily missed in a group of patients. We present a 24 year old, male patient who sustained right femoral diaphyseal and tibial plateau fractures and a patellar tendon rupture following a motor vehicle accident. The fractures were treated by open reduction internal fixation but the patellar tendon rupture was missed and the diagnosis was delayed by 7 months. Patella was migrated proximally. It was moved distally to the original location and neglected patellar tendon rupture treated successfully with modified Ecker technique. Neither preoperative traction nor additional intraoperative procedures were performed to relocate the patella to its anatomic position in the extended knee and good functional result was achieved with intensive rehabilitation.     

The role of free radicals and nitric oxide in the ischemia–reperfusion injury mediated by acute bladder outlet obstruction

Free-radical generation and nitric oxide (NO) generation were detected in the rat bladder following acute bladder outlet obstruction (BOO), and the results were compared with those for vascular ischemia and reperfusion (I-R). Forty male Sprague Dawley rats were used. In the acute BOO plus I-R group (group 1), rats were catheterized with a 3-Fr catheter and an inflated balloon was positioned at the bladder neck. The bladder was overdistended after administration of Ringer solution and furosemide (12 mg/kg, each) for 60 min, and was then drained to allow reperfusion for 30 min. In the acute BOO plus nerve stimulation group (group 2), the pelvic nerve was stimulated in the distended bladder for 60 min (5 s every 5 min, 10 V/0.1 ms, 20 Hz). Pelvic nerve stimulation was performed in nonobstructed animals in group 3. In the I-R group (group 4), the distal aorta was occluded for 60 min followed by reperfusion for 30 min. Sham-operated animals served as the control group (group 5). At the end of the protocols, the levels of hydroxyl and superoxide radicals and NO levels were measured in the bladder tissues with luminol- and lucigenin-enhanced chemiluminescence methods. The results were compared by a one-way analysis of variance test. The levels of hydroxyl radicals were not significantly different between the study groups. In contrast, superoxide radicals and NO levels were significantly increased in both group 1 and group 4 compared with those in control animals (P < 0.05 for all comparisons). Superoxide radical generation in group 2 was comparable to the levels in group 1 (P > 0.05), whereas NO levels were substantially lower than in group 1 (P = 0.06). In summary, vascular I-R causes significant oxidative damage to the bladder. Acute BOO with overdistension of the bladder mimics the effects of true vascular I-R injury. The NO pathway has possibly a major role in I-R-induced bladder damage. Prolonged BOO may therefore significantly enhance the oxidative damage to the bladder and further accentuate the effects of generalized atherosclerotic processes in the elderly adult.     

Second-Look Operation for Unresectable Pancreatic Ductal Adenocarcinoma at a High-Volume Center

Background The value of re-exploration for pancreatic ductal adenocarcinoma after the initial diagnosis of unresectability is unclear. Methods In this study, we analyzed 33 patients who were re-explored after an initial diagnosis of unresectability. Results At the time of reoperation, a resectable tumor was found in 18 patients: therefore, 15 pancreaticoduodenectomies, two total pancreatectomies and one left resection were performed with three vascular resections. Morbidity and mortality rates for the cohort were 6/33 and 1/33, without significant differences between resectable and nonresectable patients. Length of stay, duration of operation, and blood loss were significantly increased in the resection group. Kaplan–Meier survival analysis demonstrated increased median survival for resected patients (1078 days after the initial operation versus 547 days in the group of unresectable patients; p = 0.018). Analysis of the reasons against initial resection showed that, if the patients had been sent to a tertiary referral center for pancreatic surgery, a different decision in favor of resection would probably have been made in 14 out of 33 patients. A review of 10 published reports on reoperation for pancreatic cancer revealed results comparable to our study in terms of low morbidity and mortality as well as a survival benefit. Conclusions Reoperation for pancreatic ductal adenocarcinoma that is initially deemed unresectable can be safely performed in a selected group of patients by experienced surgeons, supporting the concept of patient centralization in pancreatic surgery. Resection at the second operation may confer a survival benefit even when the initial findings preclude a potentially curative approach.