Effect of Periarticular Morphine Injection for Total Knee Arthroplasty: A Randomized,Double-Blind Trial

Background

The periarticular multimodal cocktail injection including morphine is currently commonly used to treat postoperative pain after total knee arthroplasty (TKA). Despite its analgesic effect, it is frequently reported to cause nausea and vomiting, which are adverse effects of opioids. This study aimed to assess the efficacy of morphine as a component of a multimodal cocktail injection for providing postoperative analgesia and alleviating swelling in patients who underwent TKA.

Efficacy of a Pelvic Lateral Positioner With a Mechanical Cup Navigator Based on the Anatomical Pelvic Plane in Total Hip Arthroplasty

Background

The acetabular component orientation in total hip arthroplasty (THA) is of critical importance to the good clinical results. However, traditional widely used cup alignment guides for cup placement are reported to be relatively unreliable. The present study aims at comparing a novel cup alignment guide, which can be attached to our anatomical pelvic plane (APP) pelvic lateral positioner for reducing discrepancies in sagittal pelvic tilt and indicate a targeted cup angle based on the APP, with a conventional cup alignment guide.

Evaluation of the incident directional dependence of radiochromic film by use of Monte Carlo simulation and measurement

In high-precision radiotherapy, absolute and relative doses are evaluated for patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA). In our institution, we use GAFCHROMIC EBT3 (EBT3) for relative dose evaluation in IMRT QA. We usually use two directional film configurations, which are in the axial and sagittal planes. The QA in our institution shows some differences between the gamma pass rates in the axial and sagittal directions. The purpose of this study was to evaluate the incident directional dependence of EBT3 by using the percent depth dose (PDD) and the off-center ratio (OCR) between EBT3 films positioned perpendicular to the beam axis and along the beam axis. Furthermore, we compared the PDD in EBT3 films positioned perpendicular to the beam axis and the PDD by using an ionization chamber. In addition, PDDs in water phantoms with and without EBT3 films were calculated by Monte Carlo simulation. The results showed that the PDD in EBT3 films positioned perpendicular to the beam axis increased with the depth from the phantom surface. Monte Carlo simulation showed the same trend as did the film measurements. The OCR results were slightly different at dose levels below 20 %. The OCR in EBT3 films positioned along the beam axis was higher than that perpendicular to the beam axis. Thus, we conclude that EBT3 film has incident directional dependence. In IMRT QA, the gamma analysis results may be affected by the incident directional dependence of EBT3 film.     

Marmoset cytochrome P450 2J2 mainly expressed in small intestines and livers effectively metabolizes human P450 2J2 probe substrates,astemizole and terfenadine

1.?Common marmoset (Callithrix jacchus), a New World Monkey, has potential to be a useful animal model in preclinical studies. However, drug metabolizing properties have not been fully understood due to insufficient information on cytochrome P450 (P450), major drug metabolizing enzymes.

2.?Marmoset P450 2J2 cDNA was isolated from marmoset livers. The deduced amino acid sequence showed a high-sequence identity (91%) with cynomolgus monkey and human P450 2J2 enzymes. A phylogenetic tree revealed that marmoset P450 2J2 was evolutionarily closer to cynomolgus monkey and human P450 2J2 enzymes, than P450 2J forms in pigs, rabbits, rats or mice.

3.?Marmoset P450 2J2 mRNA was abundantly expressed in the small intestine and liver, and to a lesser extent in the brain, lung and kidney. Immunoblot analysis also showed expression of marmoset P450 2J2 protein in the small intestine and liver.

4.?Enzyme assays using marmoset P450 2J2 protein heterologously expressed in Escherichia coli indicated that marmoset P450 2J2 effectively catalyzed astemizole O-demethylation and terfenadine t-butyl hydroxylation, similar to human and cynomolgus monkey P450 2J2 enzymes.

5.?These results suggest the functional characteristics of P450 2J2 enzymes are similar among marmosets, cynomolgus monkeys and humans.     

Low white blood cell count is independently associated with chronic kidney disease progression in the elderly: the CKD-ROUTE study

Background

Elevated white blood cell (WBC) count is a well-known predictor of chronic kidney disease (CKD) progression. However, elderly patients commonly fail to develop a high WBC count in response to several diseased states and may instead present a low WBC count. Therefore, we hypothesized that low WBC count, in addition to high WBC count, is associated with CKD progression in the elderly.

Methods

We conducted a prospective cohort study using 3-year follow-up data from the CKD Research of Outcomes in Treatment and Epidemiology study. In the present study, participants aged over 60 years with pre-dialysis CKD stages G2–G5 were eligible. Patients were stratified into three groups according to WBC count using tertiles (T). The primary outcome was a composite of end-stage renal disease and a 50% reduction in estimated glomerular filtration rate. Data were analyzed using Cox proportional hazard models with adjustments for covariates.

Results

We enrolled 697 patients (males, 69%). The median WBC count was 6100 cells/µl (T1, <5400, n = ?222; T2, 5400–6900, n = ?235; T3, ≥6900, n = 240). During a median follow-up of 868 days, the primary outcome was observed in 170 patients, whereas 54 patients died. T1 and T3 had significantly higher hazard ratios (HR) than T2 (T1, HR 1.69, 95% confidence interval 1.14–2.51; T3, HR 1.63, 95% confidence interval 1.10–2.41). Moreover, T1 had a significantly higher adjusted HR (1.54, 95% confidence interval 1.00–2.37).

Conclusion

Low WBC count is independently associated with CKD progression in the elderly.

     

Macrophage‐derived inflammatory cytokines regulate growth factors and pain‐related molecules in mice with intervertebral disc injury

Upregulation of inflammatory cytokines and various growth factors is a significant contributor to discogenic low back pain. The aim of this study was to investigate possible regulation of pain‐related molecules by macrophages and the role of macrophage‐derived molecules in injured intervertebral disc (IVD)s. C57BL/6J mice were used in this study. We characterized the expression profiles of genes for tumor necrosis factor (TNF)‐alpha, interleukin (IL)‐1beta, nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) in both intact and injured IVDs. We examined whether macrophage depletion, induced by systemic injection of clodronate‐laden liposomes, affected the expression of these molecules in injured IVDs. The effect of TNF‐alpha on cultured F4/80‐CD11b‐cells in injured IVDs was investigated. Expression of TNF‐alpha and IL‐1beta was significantly increased in injured IVDs, but decreased by macrophage depletion. Expression of NGF and VEGF was also significantly increased, but by contrast was not decreased by macrophage depletion. TNF‐alpha treatment of F4/80‐cells from injured IVDs upregulated NGF, VEGF, cyclooxygenase (COX)‐2, and microsomal prostaglandin E synthase‐1 (mPGES1). IVD injury upregulated inflammatory cytokines and various growth factors. Macrophages in the injured IVDs produced inflammatory cytokines, but not growth factors. Macrophage‐derived inflammatory cytokines regulate growth factors and pain‐related molecules. These findings demonstrate further complexity in the pathogenesis of discogenic pain. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2274–2279, 2018.

     

Cerebral blood velocity and arterial pressure at the onset of exercise: potential influence of the cardiopulmonary baroreflex

Clinical Autonomic Research -     

Alpha-fetoprotein (AFP)- and des-gamma-carboxy prothrombin (DCP)-producing adenocarcinoma of the stomach with liver metastasis in a patient with chronic hepatitis C

A 45-year-old man was admitted to our hospital because of chronic hepatitis C and a large liver tumor accompanied by increased serum levels of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), the tumor markers for hepatocellular carcinoma. Endoscopic examination revealed advanced gastric cancer. Biopsy specimens of the stomach and liver showed gastric adenocarcinoma and its metastasis to the liver. Immunohistochemical studies demonstrated that adenocarcinoma cells both of the stomach and liver, were positive for the antibodies against AFP as well as DCP. Expression of AFP mRNA was shown in the cancer cells of the stomach. Accordingly, we diagnosed this patient with AFP- and DCP-producing adenocarcinoma of the stomach together with liver metastasis.     

Potent induction therapy with interferon and ribavirin combination therapy does not achieve a higher sustained virological response rate in chronic hepatitis C with genotype 1b and high hepatitis C virus RNA level

Aims: To compare twice-daily interferon (IFN)-beta administration and once-daily IFN-alpha-2b administration as induction therapy in ribavirin combination therapy in chronic hepatitis C with a high viral load of genotype-1b hepatitis C virus (HCV). Methods: Sixty-one chronic hepatitis patients with a high viral load of genotype-1b HCV were randomly divided into three groups: group A was given IFN-beta 6 MU induction therapy twice daily for 2 weeks; group B was given IFN-alpha-2b 6 MU induction therapy once daily for 2 weeks; and group C was given no induction therapy. All three groups were then given IFN-alpha-2b 6 MU 3 days/week for the rest of the 24-week study period. Ribavirin was given for the entire 24-week study period. Results: Although the cumulative HCV-RNA negative rates tended to be higher in group A than in group B, the differencewas not significant. The HCV-RNA negative rate at week 2 was significantly higher in groups A and B than in group C (P < 0.05). The sustained virological response (SVR) rate was 16% overall, 21% for groups A and B, and 5% for group C; the SVR rate of groups A plus B tended to be higher than that of group C (P = 0.093). Conclusions: There was no difference between the effects of the two induction therapies; potent induction therapy does achieve higher early viral clearance but not a higher SVR rate.