Effects of landiolol on the cardiovascular response during tracheal extubation

The objective of this study was to investigate the effect of landiolol on the cardiovascular responses to emergence from anesthesia and tracheal extubation. Fifty-nine patients without cardiovascular disorders who were scheduled for tympanoplasty were randomly allocated to receive a loading dose of landiolol at 0.125 mg x kg(-1) x min(-1) for 1 min, followed by an infusion at 0.01 mg x kg(-1) x min(-1) (group L1), 0.02 mg x kg(-1) x min(-1) (group L2), 0.03 mg x kg(-1) x min(-1) (group L3), or 0.04 mg x kg(-1) x min(-1) (group L4). At the end of surgery, sevoflurane and nitrous oxide were discontinued, and landiolol was started. The mean arterial pressure (MAP), heart rate (HR), and rate pressure product (RPP) in the four groups were compared before anesthesia induction, just after extubation, 5 min after extubation, 10 min after extubation, and at discharge from the operating room. Just after extubation compared with the baseline, the MAP increased significantly in all groups; the HR increased in groups L1 and L2; and the RPP increased in all groups, except for group L4. Continuous administration of landiolol, at 0.03 or 0.04 mg x kg(-1) x min(-1), may prevent the increases in HR and RPP, respectively, that occur at the emergence from anesthesia and tracheal extubation.     

Effects of metabotropic glutamate 2/3 receptor antagonists in the stress-induced hyperthermia test in singly housed mice

Rationale The stress-induced hyperthermia (SIH) test in mice has been widely used as models including some physiological aspects of psychiatric disorders. Mediated by the autonomic nervous system, SIH is commonly known to occur both before and during exposure to stress-inducing or anxiogenic situations. Recently, modulation of the group II metabotropic glutamate (mGlu) 2/3 receptor has been proposed as a novel therapeutic approach for psychiatric disorders. Objectives In the present study, we evaluated the efficacy of selective mGlu2/3 receptor antagonists and an mGlu2/3 receptor agonist in the SIH test. Results mGlu2/3 receptor antagonists such as MGS0039 and LY341495 significantly and dose-dependently reduced SIH without affecting basal rectal temperatures. In contrast, mGlu2/3 receptor agonists such as MGS0008 were ineffective in the SIH test. The attenuation of SIH by MGS0039 was significantly blocked by pretreatment with WAY100635, a serotonin 1A receptor antagonist. In contrast, an AMPA receptor potentiator, CX546 failed to reduce the SIH. Conclusions Taken together, these results suggest that the blockade of mGlu2/3 receptor may prevent stress-induced autonomic hyperactivity, and that stimulation of the postsynaptic serotonin 1A receptor, but not AMPA receptor, may be involved in this action.     

Receptor binding properties and antinociceptive effects of chimeric peptides consisting of a micro-opioid receptor agonist and an ORL1 receptor antagonist

Receptor binding properties and antinociceptive activities of chimeric peptides linked by spacers were investigated. The peptides consisted of the micro-opioid receptor ligand dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH(2)) or its analog YRFB (Tyr-D-Arg-Phe-betaAla-NH(2)) linked to the ORL1 receptor ligand Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)). All chimeric peptides were found to possess high receptor binding affinities for both micro-opioid and ORL1 receptors in mouse brain membranes although their binding affinities for both receptors in spinal membranes were significantly lower. Among them, chimeric peptide 2, which consists of dermorphin and Ac-RYYRIK-NH(2) connected by a long spacer, had the highest binding affinity towards both receptors. In the tail-flick test following intrathecal (i.t.) administration to mice, all chimeric peptides showed potent and dose-dependent antinociceptive activities with an ED(50) of 1.34-4.51 (pmol/mouse), nearly comparable to dermorphin alone (ED(50); 1.08 pmol/mouse). In contrast to their micro-opioid receptor binding profiles, intracerebroventricular (i.c.v.) administration of the chimeric peptides resulted in much less potent antinociceptive activity (ED(50) 5.55-100< pmol/mouse) than when administered i.t. (ED(50): 1.34-4.51 pmol/mouse). These results suggest the involvement of nociceptin-like agonistic effects of the Ac-RYYRIK pharmacophore in the peptides, and the regulation of mu-opioid receptor-mediated antinociception in brain. The present chimeric peptides may be useful as pharmacological tools for studies on micro-opioid receptor/ORL1 receptor heterodimers.     

Intravenous administration of MIP-1alpha with intra-tumor injection of P. acnes shows potent anti-tumor effect

Dendritic cells (DCs) play a key role as potent biological adjuvants in anti-tumor host responses. However, DC-based vaccination does not always eradicate tumors effectively. Clinical evidence suggests that a strategy to recruit a substantial number of DCs into the tumor mass might provoke proficient anti-tumor immune responses. Here we describe that myeloid DCs (mDCs) efficiently accumulate in tumor sites after intravenous injection of recombinant macrophage inflammatory protein (MIP)-1alpha when pretreated locally with adjuvants like Propionibacterium acnes. Combined treatment of tumor-bearing mice with MIP-1alpha and P. acnes also recruited a large number of natural killer cells (NK cells) to both tumor sites and regional lymph nodes (LNs) and induced a strong T helper 1 immunity at an early time. This early response later led to accumulation of CD8(+) T cells, retraction of tumors and survival of animals treated with P. acnes/MIP-1alpha. In vivo depletion of NK cells or CD8(+) T cells impaired anti-tumor effects, suggesting that activation of NK cells and CD8(+) T cells contributes to anti-tumor immunity in this model. Therefore, this study provides a novel therapeutic strategy for cancer treatment using MIP-1alpha and certain adjuvants.     

Esophageal bypass using a gastric tube and a cardiostomy for malignant esophagorespiratory fistula

Esophageal bypass with a gastric tube and a cardiostomy is a method recently devised for malignant esophagorespiratory fistula. This method separates completely the alimentary and respiratory tracts. Four patients underwent these procedures. No operative deaths occurred, nor was there any anastomotic leakage or disruption of the excluded esophagus. The average survival time was 7 months. However, all patients were allowed to consume food orally up to the last moment of life. This bypass procedure is simple and safe to perform, and is thus a feasible treatment choice for patients with such fistulas.     

Twenty-two metachronous multiple signet-ring cell carcinomas treated with repeated gastrectomies and repeated endoscopic mucosal resections: Report of a case

A 45-year-old Japanese woman underwent an endoscopic mucosal resection (EMR) for early gastric cancer at the Cancer Institute Hospital in July 1996. The patient then underwent a distal gastrectomy in 2002 because of a new early gastric cancer and repeated EMR for a total of six early gastric cancers in 2007. Finally, a total gastrectomy was performed in February 2008. The pathological examination of the resected specimen indicated 14 synchronous multiple early gastric cancers. Although the incidence of multiple gastric cancers has been reported to range from 5% to 15%, there is usually only a double or triple lesion. Moreover, multiple gastric cancer is typically observed in male elderly patients as differentiated adenocarcinomas. The present case was a young female patient and all of the lesions were intramucosal signet-ring cell adenocarcinomas. The carcinogenetic mechanism in this case may therefore be different from that in typical multiple gastric cancers. A thorough preoperative examination and regular postoperative follow-up are therefore essential for detecting multiple gastric cancers in their early stages.     

Changes in water content of intervertebral discs and paravertebral muscles before and after bed rest

Background  Although low back pain can be principally produced or increased during action, it may also be induced or enhanced in the morning after bed rest. During bed rest, tissue edema (increased water content) may occur. In this study, we measured the changes in water content in the intervertebral disc and the paravertebral muscle before and after bed rest using a magnetization transfer magnetic resonance imaging (MT-MRI) technique that permits measuring water content in tissues. Methods  A total of 20 student volunteers were enrolled in this study. MT-MRI evaluation was performed before and after bed rest. To measure water content in the intervertebral disc and paravertebral muscle, two MRI sequences were performed using MT pulse-off and MT pulse-on. Based on the two images obtained, the equivalent cross-relaxation rate (ECR) was calculated. Results  The ECR for intervertebral discs was significantly lower after bed rest than before bed rest (P < 0.01). The ECR for paravertebral equivalent cross-relaxation rate muscles was significantly higher after bed rest than before bed rest (P < 0.05). Conclusion  We obtained results indicating that after bed rest the water content in the intervertebral disc and the paravertebral muscle was increased and decreased, respectively.     

Occlusive dressing for large soft tissue defects following soft tissue tumor excision

Background  Reconstructive surgery using pedicles or free muscle-skin flaps and skin grafting reduces wound complications and promotes favorable limb function; however, the sacrifice of normal tissue remains problematic and complicated. Occlusive dressings are widely employed for management of injuries, burns, and surgical wounds. However, their effectiveness for treating soft tissue defects following a soft tissue tumor excision has not been fully elucidated. The purpose of this study was to evaluate the effectiveness and safety of an occlusive dressing treatment method for soft tissue defects following soft tissue tumor excisions. Methods  We retrospectively reviewed eight patients (three men, five women) whose wounds were treated with polyurethane foam occlusive dressings to allow reconstruction of the soft tissue defect following soft tissue tumor excision. Their mean age was 64.5 years (range 23–83 years), and the mean size of the defect was 60.1 cm² (range 20–144 cm²). The wound was covered with a hydrophilic polyurethane dressing material. The treatment periods, incidence of complications, and ultimate outcomes were evaluated. Results  Seven defects were completely healed by secondary intention without the requirement of any additional surgery. Mean treatment periods were 21.6 weeks (range 13.5–44.0 weeks). Mean follow-up periods were 33.1 months (range 15.8–48.6 months). One patient with a recurrent malignant fibrous histiocytoma (MFH) who had a history of radiotherapy required a posterior thigh flap 44 weeks after the surgery. Recurrence due to a positive surgical margin was observed in only one patient with recurrent MFH. None of the patients exhibited clinical evidence of superficial or deep infection. Conclusions  This treatment method is simple, safe, and reliable. We concluded that the highly favorable indications of this treatment are ideal for patients who wish to avoid sacrificing their normal tissue, have no history of radiotherapy before surgery, and do not require chemotherapy or radiotherapy after the operation.     

Caffeine-potentiated chemotherapy for metastatic osteosarcoma

Background

The prognosis for patients with metastatic osteosarcoma is still poor despite the development of effective adjuvant and neoadjuvant chemotherapy regimens. We have developed caffeine-potentiated chemotherapy for treatment of high-grade bone and soft tissue sarcomas based on the ability of caffeine to enhance the cytocidal effects of anticancer drugs. We report results of caffeine-potentiated chemotherapy for patients with osteosarcoma with pulmonary metastases.

Methods

We analyzed retrospectively overall survival and some prognostic factors for 41 patients with osteosarcoma/pulmonary metastases who were treated with caffeine-potentiated chemotherapy between 1990 and 2006.

Results

The mean follow-up of all patients was 32.7 months. At the time of the final follow-up, 11 patients were alive and 30 had died of disease. Overall survival rates at 2 and 5 years were 38% and 28%, respectively. We identified the primary tumor site, the histological response to preoperative chemotherapy, the number of pulmonary nodules at initial identification, the timing of pulmonary metastasis identification, and the existence of extrapulmonary metastasis as prognostic factors. Especially, the number of pulmonary nodules at initial identification and the timing of pulmonary metastasis identification were independent, strong prognostic factors. Patients with solitary pulmonary metastasis had good prognoses, and their overall 5-year survival rate was 60%; in contrast, survival was 28% in patients with two to five pulmonary nodules, and no patients with more than six nodules survived 5 years. Patients with pulmonary metastasis identified after completion of treatment had the best prognosis, whereas patients with pulmonary metastases identified during treatment had the worst prognosis.

Conclusions

Caffeine-potentiated chemotherapy prolonged survival of patients who had osteosarcoma with pulmonary metastasis. Especially, patients with pulmonary metastasis identified after completion of treatment or with a solitary pulmonary nodule had good prognoses.