A randomized, crossover, double-blinded placebo-controlled and non-blinded active drug-controlled, comparative clinical trial was conducted to evaluate the efficacy and safety of sublingual fentanyl ...tablet.
Subjects were patients treated with strong opioids at fixed intervals for chronic cancer pain and with oral morphine as rescue medication for breakthrough pain. Sublingual fentanyl was administered at doses that were 1/25th (high dose) and 1/50th (low dose) of the dose of rescue morphine and was compared with placebo and oral morphine. The primary endpoint was pain intensity difference at 30 min after administration. (Clinical Trials Government; NCT00684632).
Fifty-one patients were enrolled in the investigation. Their mean pain intensity in visual analog scale before rescue medication prior to the investigation was 60.96 (16.44, standard deviation) mm. Compared with placebo, the low and high doses of sublingual fentanyl showed significant analgesic effects (least squares mean difference, 4.54 and 8.49 mm; P = 0.014, P < 0.001, respectively). Adverse reactions were observed in 17.6%, the most common being constipation, nausea and somnolence. The incidence of adverse reactions during the high-dose administration period was higher than that during the low-dose and active control drug administration periods.
Patients treated with strong opioid analgesics at fixed intervals for chronic cancer pain and with oral morphine at doses up to 20 mg as rescue medication were investigated. The doses of sublingual fentanyl to treat breakthrough pain were determined from rescue morphine doses by use of conversion ratios. In these patients, administration of sublingual fentanyl at doses determined by a conversion ratio of 1/50 was effective and safe. Further studies are needed to validate the use of this conversion method.
We developed a mouse model of neuropathic cancer pain by inoculating Meth A sarcoma cells to the immediate proximity of the sciatic nerve in BALB/c mice. The tumor grows predictably with time and ...gradually compresses the nerve, thereby causing nerve injury. Time courses of thermal hyperalgesia and mechanical sensitivity to von Frey hairs were determined and signs of spontaneous pain were evaluated. We compared this model with the chronic constriction injury (CCI) model, which is a neuropathic pain model widely utilized in the rat. Furthermore, to characterize the difference in nerve injury between the two models, we performed histological examination of the nerve of the two models by light and electron microscopy.
Progressive compression of the sciatic nerve by growth of a tumor mass resulted in a gradual development of thermal hyperalgesia and mechanical allodynia in the ipsilateral hind paw. Signs of spontaneous pain, such as lifting of the paw, were also observed. However, further growth of the tumor reversed the mechanical hypersensitivity and produced mechanical hyposensitivity, while thermal hyperalgesia and signs of spontaneous pain still persisted. Histologically, gradual compression by the tumor resulted in a progressive damage to both myelinated and unmyelinated fibers. However, the severity of damage to the myelinated fibers was considerably less compared to that of the CCI mice. In the CCI mice, severe damage to myelinated fibers, especially large fibers, was observed and unmyelinated fibers were damaged to a lesser degree.
These results suggest that gradual compression of a nerve by a malignant tumor results in nerve damage with a profile considerably different from that of chronic constriction injury produced by loose ligation of the nerve. Our new tumor model may be useful in studies of neuropathic cancer pain due to nerve compression by malignant tumors.
Three terminal cancer patients with severe dyspnea were treated with nebulized furosemide. The underlying causes of dyspnea varied. Twenty milligrams of furosemide was nebulized and inhaled four ...times each day. Dyspnea dramatically improved and could be controlled for weeks. No noticeable side effects were observed. Inhalation of nebulized furosemide seems to be an effective and useful treatment for dyspnea in terminal cancer patients, but these observations need to be confirmed in a randomized controlled trial.
We determined whether the i.t. administration of an 18-mer phosphodiester antisense oligodeoxynucleotide (ODN) that reduces the expression of the rat NMDAR1 subunit of the N-methyl-d-aspartate (NMDA) ...receptor would affect nociceptive behaviors and prevent the development of morphine tolerance. Rats received 5 microl of i.t. saline, 30 nM antisense, or mismatch ODN twice a day for 5 days (NMDA-induced nociception, NMDA-induced thermal hyperalgesia, NR1 mRNA, and ligand binding studies) or for 3 days (formalin study). For the tolerance study, 5 days of ODNs or saline were followed by 3 days of concurrent administration of ODNs or saline (twice a day) and i.t. morphine (three times a day). Antisense, but not mismatch, results in the reduction of formalin phase 2 flinching by 50%, the spinal cord dorsal horn levels of NMDAR1 mRNA by 30%, and ligand binding by 50%. The i.t. ED(50) for NMDA-induced nociceptive behaviors is doubled, and thermal hyperalgesia is blocked by antisense treatment. The effects of antisense on NMDA-induced nociception and thermal hyperalgesia are completely reversed by discontinuing antisense. The coadministration of antisense with increasing doses of i.t. morphine for 3 days attenuates the development of morphine tolerance. These results demonstrate that an in vivo antisense targeting of the NMDAR1 subunit results in antihyperalgesic effects and a partial blockade of spinal morphine tolerance. They provide additional support for the critical role of the NMDA receptor in these forms of spinal nociception and in the development of morphine tolerance and suggest the potential therapeutic utility of this approach.
Abstract Background Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of organ transplantation that results from immunosuppression therapy. Most cases of PTLD ...derive from the B-cell lineage. T-cell PTLD, particularly natural killer (NK)/T-cell PTLD, is quite rare; only a few cases have been described. Case Report A 42-year-old woman received a living-related renal allograft from her father. Sixteen years after transplantation, the patient presented with a 1-week history of low-grade fever and epigastralgia. Computed tomography revealed intestinal masses and a right upper lung lobe mass. Gallium scintigraphy showed uptake in the abdominal mass. Epstein-Barr virus–related antibody was not detected in the patient's serum sample. We performed extirpation of the jejunum and ileum tumors. The pathologic findings showed that these 2 tumors were NK/T-cell lymphoma. After the operation, the lung mass rapidly enlarged, and right upper lobectomy was performed. The right upper lung lobe tumor showed the same histopathologic findings as the small bowel tumor. The final histologic diagnosis was established as multiple extranodal NK/T cell type PTLD of the small bowel and right upper lung lobe. Conclusions After reduction of the immunosuppressive agent, no recurrence of PTLD has been observed for the past 9 years.
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