Different strategies of mixed chimerism induction may determine stem/progenitor cell populations in recipient mice

Mixed chimerism has been suggested to induce tolerance to transplanted alloantigens. As the precise influence of mixed chimerism induction on the host organism has still not been fully elucidated, the aim of the present study was to explore this phenomenon in relation to the stem cell compartment.The experiment was performed on B6.SJL-Ptprc^aPep3^b mice. Mixed chimerism induction protocols involved 3 Gy TBI (Day − 1 of the experiment), injection of 20-30 × 10⁶ Balb C bone marrow cells (Day 0), and administration of blocking antibodies against CD40L (Day 0 and Day 4), anti-CD8 (Day − 2) with/without anti-NK1.1 (Day − 3). Selected groups of mice were also treated with cyclophosphamid (175 mg/kg) on Day 2. The presence of mixed chimerism was assessed in peripheral blood, bone marrow, and spleen, as well as in various subpopulations of leukocytes (CD4⁺, CD8⁺, CD45/B220⁺, Gr-1⁺, lin⁻/Sca-1⁺/c-kit⁻, lin⁻/Sca-1⁺/c-kit⁺, lin⁻/Sca-1⁻/c-kit⁺). Furthermore, the percentage of stem/progenitor cells (lin⁻/Sca-1⁺/c-kit⁻, lin⁻/Sca-1⁺/c-kit⁺, lin⁻/Sca-1⁻/c-kit⁺, VSEL, HSC) was analysed for the first time in bone marrow and peripheral blood of chimeric mice.The range of mixed chimerism differed significantly among various cell populations: it was lowest in CD8-positive cells and lin⁻/Sca-1⁺/c-kit⁻ cells, and highest in granulocytes. The induction of mixed chimerism revealed a significant impact on the stem/progenitor cell frequency in recipient mice, providing potential therapeutic insights into the long-term immunologic tolerance observed in chimeric mice. Collectively, these findings contribute to further optimization of mixed chimerism induction protocols and might help in the introduction of this phenomenon into clinical practice.     

Caudal ropivacaine and neostigmine in pediatric surgery

BACKGROUND: Neostigmine has been added to local anesthetics for different nerve blocks. This study was conducted to evaluate effects of neostigmine when added to ropivacaine for caudal anesthesia. METHODS: We studied children, aged 1-5 yr, undergoing inguinal hernia and hypospadias surgery. After standard induction of anesthesia, Group I received 0.2% ropivacaine 0.5 ml/kg and Group II received 0.2% ropivacaine 0.5 ml/kg with 2 microg/kg neostigmine via the caudal route. Heart rate, mean arterial pressure, and pulse oximetry were recorded before induction, after induction, and then every 10 min after caudal anesthesia. Hemodynamic, Toddler-Preschooler Postoperative Pain Scale pain score, and sedation score values were recorded 30 min after extubation and at hours 2, 4, 6, 12, and 24. A pain score greater than 3/10 resulted in administration of rectal paracetamol. RESULTS: There were no differences between the groups in demographic and hemodynamic data, duration of surgery and anesthesia, time to extubation, or sedation scores. The pain scores were significantly lower in Group II at 6 and 12 h (P < 0.05). Time to first analgesic requirement was statistically prolonged in Group II (19.2 +/- 5.5h) when compared with Group I (7.1 +/- 5.7 h) (P < 0.05). Total analgesic consumption was statistically larger in Group I (174 +/- 96 mg) when compared with Group II (80 +/- 85.5 mg) (P < 0.05). The incidence of vomiting (3 patients in Group II and 1 patient in Group I) was not statistically significantly different. CONCLUSIONS: The authors found that a single caudal injection of neostigmine when added to ropivacaine offers an advantage over ropivacaine alone for postoperative pain relief in children undergoing genitourinary surgery.     

Efficacy and safety of daclatasvir‐based antiviral therapy in hepatitis C virus recurrence after liver transplantation. Role of cirrhosis and genotype 3. A multicenter cohort study

Direct‐acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in the recurrence of hepatitis C virus (HCV) infection after liver transplant (LT). However, its effect on the severe recurrence and the risk of death remains controversial. We evaluated the efficacy, predictors of survival, and safety of DAC‐based regimens in a large real‐world cohort. A total of 331 patients received DCV‐based therapy. Duration of therapy and ribavirin use were at the investigator's discretion. The primary end point was sustained virological response (SVR) at week 12. A multivariate analysis of predictive factors of mortality was performed. Intention‐to‐treat (ITT) and per‐protocol SVR were 93.05% and 96.9%. ITT‐SVR was lower in cirrhosis (n = 163) (96.4% vs. 89.6% P = 0.017); the SVR in genotype 3 (n = 91) was similar, even in advanced fibrosis (96.7% vs. 88%, P = 0.2). Ten patients (3%) experienced virological failure. Therapy was stopped in 18 patients (5.44%), and ten died during treatment. A total of 22 patients (6.6%) died. Albumin (HR = 0.376; 95% CI 0.155–0.910) and baseline MELD (HR = 1.137; 95% CI: 1.061–1.218) were predictors of death. DCV‐based DAA treatment is efficacious and safe in patients with HCV infection after LT. Baseline MELD score and serum albumin are predictors of survival irrespective of viral response.     

Torsion of a mesenchymal hamartoma of the liver in a 1-year-old boy

We report a case of a one-year-old boy who was referred to our clinic suspected of having acute abdomen. On physical examination, the abdomen was soft, diffusely tender with weak peristalsis. Ultrasonography and MRI of the right hemiabdomen demonstrated a well-defined, solid, expansive formation with slightly lobulated contours and an interspersed inhomogeneous structure with overall dimensions of 59?×?45?×?50?mm. After midline laparotomy was performed, a cystic tumor was found, twisted around a pedicle which was arising from the falciform ligament and it measured 5–6?cm in diameter. The tumor appeared to be necrotic. The mass was ligated and extirpated on the pedicle and sent for histopathological analysis. After the surgery, the boy was hemodynamically stable, without respiratory complications and all laboratory findings were within normal limits. Histopathological analysis showed that the tumor was composed of mesenchymal stroma with sparse glimpses of hepatocytes and bile ducts with partly cystic changes lined by orderly epithelium. Given the clinical data, histology and immunohistochemistry analysis (alpha-fetoprotein, CK8/18, hepatocyte, desmin and CD31) a diagnosis of a twisted mesenchymal hamartoma of the liver was made.     

Intravenous paracetamol improves the quality of postoperative analgesia but does not decrease narcotic requirements

Paracetamol, a centrally acting inhibitor of cyclooxygenase, has less gastrointestinal and platelet-inhibiting side effects and is clinically better tolerated than nonsteroidal anti-inflammatory drugs. Therefore, it will be ideally suited for postoperative pain relief. In this prospective, double-blind, randomized, placebo-controlled study, we evaluated the analgesic efficacy, opioid-sparing effect and effects on opioid-related adverse effects of intravenous (IV) paracetamol in combination with IV morphine after lumbar laminectomy and discectomy. Forty patients were divided into 2 groups (n=20 each) to receive either paracetamol 1 g (group 1) or 0.9% NaCl 100 ml (group 2) at the end of the operation and at 6-hour intervals over 24 hours. IV patient-controlled analgesia with morphine was used as a rescue analgesic in both groups. Pain was evaluated at rest and on movement at the 1st, 2nd, 4th, 6th, 12th, 18th, and 24th hours using a visual analog scale. Hemodynamic parameters, morphine usage, patient satisfaction, and probable side effects were also evaluated. Pain scores at rest and on movement at the 12th, 18th, and 24th hours were significantly lower in group 1 (P<0.001). Morphine consumption was not statistically significantly different between the groups (P>0.05). Vomiting in group 2 was significantly higher (P=0.027). Significantly more patients in the paracetamol group rated their pain management as excellent (45% vs. 5%). Although repeated IV paracetamol usage after lumbar laminectomy and discectomy did not demonstrate a significant opioid-sparing effect, it did decrease visual analog scale scores at certain evaluation times and incidence of vomiting and increase patient satisfaction.     

In vitro activity of tigecycline against resistant micro-organisms isolated from burn patients

Infections in burn patients are usually caused by multidrug-resistant micro-organisms. Tigecycline, a derivative of glycylcyclines, is an effective antibiotic against the resistant strains. The aim of this study is to determine the in vitro activity of tigecycline against the multidrug-resistant bacteria isolated from burn patients. Fourty-seven bacteria isolated from 118 patients hospitalized in the burn unit during 2003-2006 were included in the study. Gram-negative bacteria that were resistant to at least six broad-spectrum antibiotics, methicillin-resistant staphylococci and ampicillin-resistant enterococci were studied. Minimal inhibitory concentration values of tigecycline against these bacteria were tested by E-test strips. Susceptibility breakpoints were determined according to the previous studies; 相似文献   

Combined low‐dose flutamide plus finasteride vs low‐dose flutamide monotherapy for recurrent prostate cancer: a comparative analysis of two phase II trials with a long‐term follow‐up

OBJECTIVE

To compare the efficacy and tolerability of peripheral androgen blockade using combined low‐dose flutamide plus finasteride vs low‐dose flutamide monotherapy for treating biochemical relapse after the definitive management of prostate adenocarcinoma.

PATIENTS AND METHODS

Fifty‐six men treated for biochemical relapse of prostate cancer were enrolled prospectively in a phase II trial at the Walter Reed Army Medical Center from 1997 to 2001. Thirty‐six men were treated with flutamide (125 mg twice daily) and finasteride (5 mg twice daily), and 20 men received low‐dose flutamide only after biochemical recurrence (prostate‐specific antigen, PSA, level ≥0.4 ng/mL). Cox proportional hazards analyses were used to compare the risk of progression between the groups.

RESULTS

Patients on combined and monotherapy had a median follow‐up of 54 and 43.5 months, respectively. Seven men (19%) in the combined arm remain in the study with no progression, while five (25%) on monotherapy continue and are progression‐free. Men on combined therapy had a greater decrease in their PSA level (P = 0.002). Multivariate analysis showed that men on combined therapy had significantly less risk of progression than men on monotherapy (hazard ratio 0.21, 95% confidence interval 0.07–0.63, P = 0.005). There was no significant difference in the frequency of side‐effects between the groups. Toxicities were reported to be mild.

CONCLUSIONS

Our analysis suggests the therapeutic value of low‐dose flutamide alone or combined with finasteride as first‐line agents in a possible graduated approach for treating PSA‐only recurrent prostate cancer. Due to unwanted metabolic effects associated with traditional hormonal agents, phase III trials comparing both regimens with current therapies are warranted.     

Migration of biliary plastic stents: experience of a tertiary center

Background and study aims  Stent migration occurs in about 5–10% of patients undergoing biliary stenting. The aim of this study was to analyze the risk factors for stent migration in patients with benign and malignant strictures. Patients and methods  We retrospectively analyzed records of 524 biliary plastic stent placement procedures. Details noted included the cause and localization of stricture, characteristics and number of stents, direction of stent migration, presentation of patient with migrated stent, and the methods used for retrieval of migrated stents. Results  Two hundred and four (38.9%) of the procedures were performed for benign biliary strictures (BBS) and 320 (61.1%) for malignant biliary strictures (MBS). Thirty-four patients had 45 migrated biliary stents. The rate of migration was 8.58% (proximal 4.58% and distal 4.00%). Migration frequency was higher in BBS compared with MBS (13.7% versus 5.3%, p = 0.001). In BBS, the rate of stent migration was higher in cases with one (19.3%) and two stents (20.9%) when compared with cases with multiple stents (2.7%) (p = 0.001; p = 0.001, respectively). Migration occurred more frequently (10.9%) in cases with two stents when compared both to cases with one stent (3.0%) and those with multiple stents (0%) in MBS (p = 0.008; p = 0.020, respectively). In BBS, short stents migrated more frequently proximally (77%) and long stents more frequently distally (73%) (p = 0.008). In BBS, migration in cases with proximal stricture occurred more frequently distally (76.9%), while in those with distal stricture, migration was more frequently proximal (73.3%) (p = 0.008). All of the proximally migrated stents could be successfully retrieved endoscopically. Conclusions  The risk of stent migration is higher in BBS compared with in MBS. The cases with multiple stents had significantly lower stent migration. In BBS, long stent, proximal and postcholecystectomy strictures were associated with distal migration, while short stent, distal and non-postcholecystectomy strictures were associated with proximal migration.     

Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment

To assess platelet function profiles in diabetic and nondiabetic patients on aspirin and clopidogrel therapy, two patient populations were included to investigate the 1) acute effects of a 300-mg clopidogrel loading dose (group 1, n = 52) and 2) long-term effects of clopidogrel (group 2, n = 120) on platelet function in diabetic compared with nondiabetic patients already on aspirin treatment. Patients were stratified according to the presence of type 2 diabetes. Platelet aggregation was assessed using light transmittance aggregometry (groups 1 and 2). Platelet activation (P-selectin expression and PAC-1 binding) was determined using whole-blood flow cytometry (group 2). Clopidogrel response was also assessed. In group 1, platelet aggregation was significantly increased in diabetic (n = 16) compared with nondiabetic (n = 36) patients at baseline and up to 24 h following a 300-mg loading dose (P = 0.005). In group 2, platelet aggregation and activation were increased in diabetic (n = 60) compared with nondiabetic (n = 60) subjects (P < 0.05 for all platelet function assays). Diabetic subjects had a higher number of clopidogrel nonresponders (P = 0.04). Diabetic patients have increased platelet reactivity compared with nondiabetic subjects on combined aspirin and clopidogrel treatment. Reduced sensitivity to antiplatelet drugs may contribute to the increased atherothombotic risk in diabetic patients.