The dose-related effects of ketamine on mortality and cytokine responses to endotoxin-induced shock in rats

In our previous study, ketamine administration was found to inhibit hypotension, metabolic acidosis, and cytokine responses in endotoxemia. However, only a few studies have indicated whether ketamine has the dose-related beneficial effects after endotoxin injection. Our objective was to clarify the dose-related effects of ketamine on mortality and cytokine responses to endotoxemia in rats. Sixty-five rats were divided at random among five equal groups: Group C was given saline alone. Group E was given endotoxin alone (Escherichia coli endotoxin; 10 mg/kg, IV). Group L received a a low dose of ketamine (5 mg.kg(-1).h(-1), IV), Group M a medium dose of ketamine (10 mg.kg(-1).h(-1), IV), and Group H a high dose of ketamine (20 mg.kg(-1).h(-1), IV), all exposure to endotoxin. After endotoxin injection, hemodynamics, acid-base status, mortality rate, and plasma concentrations of tumor necrosis factor alpha and interleukin 6 were assessed for each of the five groups. Endotoxin injection produced progressive hypotension, metabolic acidosis, and a large increase in plasma cytokine concentrations. Mortality rates 8 h after endotoxin injection were 0% for group C, 92% for group E, 48% for group L, 0% for group M, and 32% for group H. Ketamine administration thus clearly had a beneficial effect on mortality rates, with that for group M lower than for groups L and H (P < 0.05). The cytokine responses to endotoxin were somewhat suppressed in group M but not in group L. Ketamine administration dose-independently inhibited hypotension, metabolic acidosis, and cytokine responses in rats injected with endotoxin.     

Mini-dose (0.05 mg) intrathecal morphine provides effective analgesia after transurethral resection of the prostate

PURPOSE: To determine the optimal dose of intrathecal morphine that produces satisfactory analgesia with minimum side effects in elderly patients undergoing transurethral resection of the prostate (TURP). METHODS: In this double-blind prospective study, 42 patients undergoing TURP with spinal anesthesia were allocated to one of three groups. Group A (n = 14) received tetracaine, 10 mg, alone. Group B (n = 13) and Group C (n = 15) received morphine 0.05 mg and 0.10 mg, respectively, in combination with tetracaine. Postoperative pain, nausea and pruritus were evaluated using visual analogue scales (VAS). SpO(2) and respiratory rate were also assessed. RESULTS: At three, five, seven and 24 hr after spinal anesthesia, the VAS scores for pain in Groups B and C were significantly less than in Group A. Group C experienced significantly greater VAS scores for pruritus as compared to Groups A and B. There was no significant difference in the intensity of nausea among the three groups. No patient experienced hypoxemia (SpO(2) < 90%) and respiratory depression (respiratory rate < 10 beats*min(-1)) in any group. CONCLUSION: A dose of 0.05 mg in intrathecal morphine with spinal anesthesia would be optimal for elderly patients undergoing TURP.     

Perioperative Treatment with Infliximab in Patients with Crohn’s Disease and Ulcerative Colitis is Not Associated with an Increased Rate of Postoperative Complications

Purpose  The impact of infliximab (IFX) on postoperative complications in surgical patients with Crohn’s disease (CD) and ulcerative colitis (UC) is unclear. We examined a large patient cohort to clarify whether a relationship exists between IFX and postoperative complications. Methods  A total of 413 consecutive patients—188 (45.5%) with suspected CD, 156 (37.8%) with UC, and 69 (16.7%) with indeterminate colitis—underwent abdominal surgery at the Massachusetts General Hospital between January 1993 and June 2007. One hundred one (24.5%) had received preoperative IFX ≤ 12 weeks before surgery. These patients were compared to those who did not receive IFX with respect to demographics, comorbidities, presence of preoperative infections, steroid use, and nutritional status. We then compared the cumulative rate of complications for each group, which included deaths, anastomotic leak, infection, thrombotic complications, prolonged ileus/small bowel obstruction, cardiac, and hepatorenal complications. Potential risk factors for infectious complications including preexisting infection, pathological diagnosis, and steroid or IFX exposure were further evaluated using logistic regression analysis. Results  Patients were similar with respect to gender (IFX = 40.6% men vs. non-IFX = 51.9%, p = 0.06), age (36.1 years vs.37.8, p = 0.43), Charlson Comorbidity Index (5.3 vs. 5.7, p = 0.25), concomitant steroids (75.3% vs. 76.9%, p = 0.79), preoperative albumin level (3.3 vs. 3.2, p = 0.36), and rate of emergent surgery (3.0% vs. 3.5%, p = 1.00). IFX patients had higher rates of CD (56.4% vs. 41.9%, p = 0.02), concomitant azathioprine/6-mercaptopurine use (34.6% vs. 16.6%, p < 0.0001), and lower rates of intra-abdominal abscess (3.9% vs. 11%, p < 0.05). After surgery, the two groups had similar rates of death (2% vs. 0.3% p = 0.09), anastomotic leak (3.0% vs. 2.9%, p = 0.97), cumulative infections (5.97% vs. 10.1%, p = 1), thrombotic complications (3.6% vs. 3.0%, p = 0.06), prolonged ileus/small bowel obstructions (3.9 vs. 2.8, p = 0.59), cardiac complications (1% vs. 0.6%, p = 0.42), and hepatic or renal complications (1.0 vs. 0.6% p = 0.72). A logistic regression model was then created to assess the impact of IFX, as well as other potential risk factors, on the rates of cumulative postoperative infections. We found that steroids (odds ratio [OR] = 1.2, p = 0.74), IFX (OR 2.5, p = 0.14), preoperative diagnosis of CD (OR = 0.7, p = 0.63) or UC (OR = 0.6, p = 0.48), and preoperative infection (OR = 1.2, p = 0.76) did not affect rates of clinically important postoperative infections. Conclusions  Preoperative IFX was not associated with an increased rate of cumulative postoperative complications. Dr. Sands has received research grants and honoraria for lecturing and consulting from Centocor.     

Down-regulation of HLA class I antigens in prostate cancer tissues and up-regulation by histone deacetylase inhibition

PURPOSE: HLA class I down-regulation in cancer cells confers immunological escape from cytotoxic T lymphocytes. We assessed the frequency of down-regulation of HLA class I antigens in a large series of prostate cancer tissues and determined the mechanism of up-regulation by investigating prostate cancer cell lines. MATERIALS AND METHODS: Immunohistochemical staining for HLA class I was done in specimens of 419 prostate cancers. We also investigated clinicopathological parameters, and the relationships between HLA class I down-regulation and the parameters. Furthermore, we examined whether HLA down-regulation was caused by epigenetic changes in vitro. RESULTS: HLA class I was down-regulated in 311 prostate cancers (74.2%) and it significantly correlated with beta2-microglobulin down-regulation and a higher clinical stage. Flow cytometric analysis revealed a low level of HLA class I in LNCaP cells, which was up-regulated by the histone deacetylase inhibitor trichostatin A (Sigma). Trichostatin A up-regulated LNCaP beta2-microglobulin at the protein level. Furthermore, chromatin immunoprecipitation assay using an anti-acetylated histone H3 antibody provided direct evidence that trichostatin A up-regulated beta2-microglobulin by modulating the acetylation status of the promoter region in LNCaP cells. CONCLUSIONS: The current study shows that the prevalence of HLA class I down-regulation is high in prostate cancer but histone deacetylase inhibitors can up-regulate HLA class I in LNCaP cells by up-regulating beta2-microglobulin. We suggest that the combination of an immunotherapeutic approach and histone deacetylase inhibition would accentuate the effects of current immunotherapies for prostate cancer.     

A new method of primary engineering of esophagus using orthotopic in-body tissue architecture

PurposeTissue engineering of esophagus is required for management of long-gap esophageal atresia (LGEA). Collagenous connective tissue membranes fabricated by in-body tissue architecture (iBTA), called biosheets, can repair esophageal defects and generate tissues similar to native esophagus. However, iBTA requires second-stage surgery because of heterotopic preparation of biosheets. Our aim was to develop orthotopic iBTA for primary engineering of the esophagus by interposing a tubular mold to the esophageal defect.MethodThe cervical esophagus of six rats was transected. An acrylic tube (internal diameter 2.6 mm, length 7.0 mm) was inserted and fixed between the ends of the upper and lower esophagus, and a 3 mm-long esophageal defect was created. Four weeks later, the rats were sacrificed for histological analysis.ResultsPostoperatively the rats could intake liquid food. After four weeks, the esophageal defects were filled with regenerated tissues. Histologically the new esophageal walls stained positive for collagen type I. The inner surfaces were covered with stratified squamous epithelium that expressed pan-cytokeratin. In only one of six rats, regeneration of muscular-like tissue was suggested by positive immunohistochemical staining for desmin.ConclusionOrthotopic iBTA can regenerate a substitute esophagus with esophageal epithelium and collagenous wall. This technique may be a novel treatment for esophageal atresia with gaps of various lengths including LGEA.     

Massive ascites after living donor liver transplantation with a right lobe graft larger than 0.8% of the recipient’s body weight

Shirouzu Y, Ohya Y, Suda H, Asonuma K, Inomata Y. Massive ascites after living donor liver transplantation with a right lobe graft larger than 0.8% of the recipient’s body weight.
Clin Transplant 2010: 24: 520–527.
© 2009 John Wiley & Sons A/S. Abstract: Background: There are only limited data on post‐transplant ascites unrelated to small‐sized grafts in living donor liver transplantation (LDLT). Methods: The subjects were 59 adult patients who had received right lobe LDLT with a graft weight‐to‐recipient weight ratio (GRWR) > 0.8%. Patients were divided into either Group 1 (n = 14, massive ascites, defined as the production of ascitic fluid > 1000 mL/d that lasted longer than 14 d after LDLT) or Group 2 (n = 45, no development of massive ascites). Patients were followed for a median period of 3.0 yr (range, 0.5–7.5 yr). Results: Group 1 had both higher Model for End‐Stage Liver Disease score and Child‐Pugh score than Group 2. Portal venous flow volume just after reperfusion was significantly greater in Group 1 than Group 2 (307.8 ± 268.8 vs. 176.2 ± 75.0 mL/min/100 g graft weight, respectively; p < 0.05). Post‐transplant infectious complications including ascites infection developed more frequently within the first post‐transplant month in Group 1. Massive ascites was significantly associated with early graft loss (p < 0.05). Conclusion: Post‐transplant massive ascites associated with portal over‐perfusion into the graft liver can develop in patients with a GRWR over 0.8%. Recipients with post‐transplant massive ascites require careful management to prevent infection.     

Successful pregnancy after gonadotropin-releasing hormone analogue and hysteroscopic myomectomy in a woman with diffuse uterine leiomyomatosis

We report a patient with diffuse uterine leiomyomatosis, who wished to become pregnant. We performed hysteroscopic myomectomy after treatment with nafarelin acetate for 6 months. The patient conceived spontaneously soon after hysteroscopic myomectomy, and delivered a 2,798-g healthy baby.     

Acute retrobulbar optic neuritis with anti-myelin oligodendrocyte glycoprotein antibody-associated disease complicated with microscopic polyangiitis: A case report

Rationale:Anti-myelin oligodendrocyte protein antibody-associated disease (MOGAD) is a new disease entity with various clinical phenotypes. MOGAD often present with recurrent optic neuritis (ON), and it can also develop as a compartment of neuromyelitis optica spectrum disorder (NMOSD). Moreover, multiple autoantibodies such as an anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) had been reported in the serum of patients with NMOSD.Patient concerns:We report an 86-year-old woman with a 2-year history of microscopic polyangiitis (MPA). The patient had a rapid loss of vision in her left eye. No abnormal findings were observed on her left fundus, and she tested negative for MPO-ANCA upon admission. However, anti-MOG antibodies were observed in the patient''s serum and cerebrospinal fluid.Diagnosis:A diagnosis of MOGAD complicated with MPA was made.Interventions:The patient received twice steroid pulse therapy and oral azathioprine as maintenance therapy.Outcomes:Her vision rapidly recovered, and no subsequent relapse was observed during the 8-month observation period.Conclusion:To the best of our knowledge, this is the first case of MOGAD complicated with MPA, and steroid pulse therapy and azathioprine therapy were effective for ON caused by MOGAD.