Absence of TNFRp55 influences virus-induced autoimmunity despite efficient lymphocytic infiltration

Tumor necrosis factor (TNF)-alpha is a multipotent cytokine associated with many cellular functions, including inflammation and anti-viral defense. Many studies have implicated TNF-alpha in the pathogenesis of autoimmune diseases. TNF-alpha responses are mediated through binding to specific cell surface receptors, TNFRp55 and TNFRp75. The objective of the present study was to investigate the contribution of the TNFRp55 in the inflammatory response associated with autoimmune diabetes development in a viral transgenic model. In this model, the animals express lymphocytic choriomeningitis virus (LCMV)-glycoprotein (gp) in the beta cells of the pancreas under the control of the rat insulin promoter (RIP-gp). Diabetes is induced following LCMV infection due to beta cell destruction by LCMV-specific CD8+ cytotoxic T lymphocytes. TNFRp55-deficient RIP-gp animals were examined to assess the importance of the TNFRp55. The kinetics and onset of lymphocytic infiltration into the pancreatic islets and hyperglycemia was not altered in the absence of TNFRp55 after LCMV infection. Animals were evaluated following recombinant LCMV-gp vaccinia virus infection to test whether properties of the infectious agent influence autoimmunity. Interestingly, the kinetics were accelerated and the frequency of diabetes was increased in TNFRp55-deficient mice compared with control animals. This accelerated onset of diabetes is likely a result of increased viral replication in the TNFRp55-deficient host. Thus, these data demonstrate that TNFRp55 is not essential for producing the local inflammatory effects which contribute to organ-specific autoimmunity in this transgenic model. However, the absence of TNFRp55 altered the kinetics and incidence of the disease in a pathogen-dependent fashion.      

A three-country comparison of psychotropic medication prevalence in youth

Background  

The study aims to compare cross-national prevalence of psychotropic medication use in youth.     

Intracranial tumors examined by intraarterial DSA: a comparative angiography study

We compared intraarterial digital subtraction angiography (DSA) studies with those of conventional angiography, performed for 24 patients who had intracranial tumors. Intraarterial DSA is more effective in evaluating tumoral blush and venous phase, but neovascularization can be judged better by conventional angiography. In most cases, intraarterial DSA can replace conventional angiography for the diagnostic and preoperative evaluation of intracranial tumors. However, conventional angiography remains the technique of choice for the evaluation of neovascularization or if the patient is not cooperative.     

Subfascial hematoma progressed to arm compartment syndrome due to a nontransposed brachiobasilic fistula

Vascular access-associated compartment syndrome is reported rarely in hemodialysis patients. A 62-year-old female hemodialysis patient experienced left-arm compartment syndrome caused by a nontransposed brachiobasilic arteriovenous fistula. A subfascial hematoma that developed because of perforation of the posterior wall of the basilic vein was not detected by Doppler ultrasound initially, and subsequent heparinized hemodialysis caused progression of the hematoma. Neuromuscular sequelae were prevented by performing an emergent fasciotomy, and transposition of the arterialized basilic vein was performed later to prevent similar complications in the future. This case report shows the risk for the occurrence of such a devastating complication if the nontransposed brachiobasilic fistula is used for hemodialysis vascular access.     

Pharmacokinetics of continuous intravenous and subcutaneous infusions of cytosine arabinoside

The pharmacokinetics of continuous subcutaneous cytosine arabinoside (ara-C) infusions were compared with continuous intravenous infusions. Steady-state serum ara-C levels and myelosuppression were similar with both routes of administration. CSF/serum ara-C ratios ranged from 0.14 to 0.91 (mean, 0.58). Continuous subcutaneous ara-C infusions were a convenient and reliable alternative to intravenous infusions.     

The structure of the T cell gamma chain gene in lymphoproliferative disorders and lymphoma cell lines [published erratum appears in Blood 1987 Jan;69(1):368]

During the development of B and T cells, a number of genes undergo rearrangement. In this paper we have studied the structure of the T cell gamma-chain gene in primary lymphomas and cell lines derived from patients with lymphoma. Samples derived from patients with angioimmunoblastic lymphadenopathy (AIL), Lennert's lymphoma, and Hodgkin's disease were also examined. TcR gamma was rearranged in all T cell lymphomas and in some B cell lymphomas and B cell lymphoma cell lines. Rearrangement of the gamma-chain gene was also found in AIL, Lennert's lymphoma, and four of eight cases of Hodgkin's disease. These studies indicate that rearrangement of TcR gamma is a useful clonal marker but does not aid in the identification of cell lineage.     

Postprison Release HIV-Risk Behaviors in a Randomized Trial of Methadone Treatment for Prisoners

Background: This secondary analysis examined the impact of methadone initiated in prison on postrelease HIV risk behaviors. The parent study was a three-group randomized clinical trial in which participants received drug abuse counseling in prison and were randomly assigned to: (1) passive referral to substance abuse treatment upon release; (2) guaranteed methadone treatment admission upon release; and (3) methadone in prison and guaranteed continuation of methadone upon release. Methods: Participants were 211 adult males with preincarceration histories of opiate dependence. The AIDS Risk Assessment was administered at baseline (in prison) and at 1-, 3-, 6-, and 12-month postrelease. Data were analyzed for the entire sample (N = 211) as well as the subsamples who reported injecting drugs in the 30 days prior to incarceration (n = 131) and who reported having unprotected sex in that time frame (n = 144) using generalized linear mixed model on an intent-to-treat basis. Results: There were no significant changes in sex- or drug-risk by Condition over Time. There were significant Time and Condition main effects for the total sample as well as the injector subsample for drug-risk behaviors. There were no significant Condition main effects for HIV sex-risk behaviors, but there were significant Time main effects. Conclusions: Methadone initiated in prison or immediately postrelease is associated with reduced HIV drug-risk compared to counseling in prison without methadone and passive referral to treatment at release. Participation in several drug- and sex-risk behaviors also showed significant declines during the postrelease time periods. (Am J Addict 2012;21:476-487).     

Utilization of a colony assay to assess the variables influencing elimination of leukemic cells from human bone marrow with monoclonal antibodies and complement

We have previously used a chromium-release assay to demonstrate that the cocktail of monoclonal antibodies BA-1, BA-2, BA-3, and complement can effectively lyse human leukemic cells in the presence of excess bone marrow. Using a leukemic cell colony assay, we have reinvestigated the variables influencing lysis of human leukemic cells (KM-3, HPB- NULL, NALM-6) in bone marrow using BA-1, BA-2, BA-3, and complement. Specific variables addressed included the concentration of excess bone marrow cells, the number of treatments, the presence or absence of DNase during the treatment, the combination of antibodies, and the sensitivity of different leukemic cell lines to lysis. Using the colony assay, the BA-1,2,3 cocktail was shown to be more effective than any single antibody or combination of two antibodies. We also determined that the concentration of excess bone marrow cells and number of treatments had a direct bearing on leukemic cell lysis. Although two cycles of treatment were significantly superior to one cycle, three cycles were not significantly superior to two cycles. Inclusion of DNase (10 micrograms/mL) was a critical adjunct that eliminated clumping and facilitated plating cells in the colony assay. Finally, we could show that striking differences existed in the sensitivity of the leukemic cell lines to lysis with the BA-1,2,3 cocktail and complement. NALM-6 cells were the most sensitive (approximately four logs of kill), and KM-3 cells were the most resistant (less than two logs of kill). Our results strongly support the utility of sensitive leukemic cell colony assays in the analysis of marrow treatment variables in autologous bone marrow transplantation.     

A systematic review of patient reported outcomes and patient experience in enhanced recovery after orthopaedic surgery

Introduction

Orthopaedic enhanced recovery after surgery (ERAS) providers are encouraged to estimate the actual benefit of ERAS according to the patient’s opinion by using patient generated data alongside traditional measures such as length of stay. The aim of this paper was to systemically review the literature on the use of patient generated information in orthopaedic ERAS across the whole perioperative pathway.

Methods

Publications were identified using Embase^™, MEDLINE^®, AMED, CINAHL^® (Cumulative Index to Nursing and Allied Health Literature), the Cochrane Library and the British Nursing Index. Search terms related to experiences, acceptance, satisfaction or perception of ERAS and quality of life (QoL).

Findings

Of the 596 abstracts found, 8 papers were identified that met the inclusion criteria. A total of 2,208 patients undergoing elective hip and knee arthroplasty were included. Patient satisfaction was reported in 6 papers. Scores were high in all patients and not adversely affected by length of stay. QoL was reported in 2 papers and showed that QoL scores continued to increase up to 12 months following ERAS. Qualitative methods were used in one study, which highlighted problems with support following discharge. There is a paucity of data reporting on patient experience in orthopaedic ERAS. However, ERAS does not compromise patient satisfaction or QoL after elective hip or knee surgery. The measurement of patient experience should be standardised with further research.     

Combined pancreaticoduodenectomy and colon resection for locally advanced peri-ampullary tumours: analysis of peri-operative morbidity and mortality

Background

Combined pancreaticoduodenectomy (PD) and colonic resection may be necessary to achieve an R0 resection of peri-ampullary tumours. The aim of this study was to examine the morbidity and mortality associated with this procedure.

Methods

A retrospective cohort study was performed comparing 607 patients who underwent a standard pancreaticoduodenectomy (S-PD) to 28 patients who had a concomitant colon resection and PD (PD-colon) over a 10-year period at an academic centre.

Results

Patients in the PD-colon group were more likely to have received neoadjuvant chemotherapy ± radiation (3/28, 11% versus 14/607, 2%, P = 0.024). Operative time was also longer (530 versus 410 min, P < 0.001) and they were more likely to have had portal vein resections (9/28, 32% versus 76/607, 13%, P = 0.007). There was no difference in the intra-operative blood loss, length of stay, or overall complication rates. The PD-colon group had a higher rate of severe post-operative bleeding (4/28, 11% versus 8/607, 1%, P = 0.002). The post-operative mortality rates for the PD-colon and PD groups were 2/28 (7%) and 8/607 (1%), respectively (P = 0.068).

Conclusions

PD-colon has an acceptable risk of peri-operative morbidity compared with S-PD in well-selected patients.