The effect of antinociceptive drugs tested at different times after nerve injury in rats

Given the evolving nature of anatomical and functional changes in the nervous system that are involved in the development of neuropathic pain, it is possible that the differing time course after injury underlies the inconsistent efficacy of drugs in neuropathic pain patients. In the current study, we evaluated the behavioral effects of two standard drugs used clinically for neuropathic pain, the anticonvulsant gabapentin and antidepressant imipramine, in rats at different times after peripheral nerve injury. Rats that underwent the spared nerve injury procedure responded to an innocuous mechanical stimulus (von Frey filament) 2, 4, and 8 wk after injury. Gabapentin dose-dependently suppressed mechanical sensitivity at all time points tested but the potency of gabapentin was three-fold less 4 wk postinjury (135 mg/kg) compared with 2 and 8 wk postinjury (41 and 44 mg/kg, respectively). In contrast, imipramine lacked significant efficacy at 2 and 8 wk postinjury but slightly attenuated mechanical hypersensitivity at 4 wk postinjury. The results show that drug effects may change over time in the neuropathic state, which should be an important consideration in the evaluation of drugs in preclinical animal pain models and has implications for temporal approaches to therapy in the clinic.     

Post-chemotherapy nerve-sparing retroperitoneal lymph node dissection for advanced germ cell tumor

Objective:   To report our experience with post-chemotherapy nerve-sparing retroperitoneal lymph node dissection (RPLND) for advanced germ cell tumor (GCT).
Methods:   Between 1994 and 2008, 92 patients with advanced GCT underwent RPLND after multiple treatments with systemic chemotherapy at our institution. A nerve-sparing RPLND was carried out in 78 patients (84.8%; median age 32 years). Of them, 19 had a seminoma and 59 had a non-seminoma.
Results:   Lumbar splanchnic nerves controlling ejaculatory function were macroscopically preserved during RPLND. Bilateral and unilateral lumbar splanchnic nerves were preserved in 40 patients and 38 patients, respectively. Sixty-five patients could be evaluated for ejaculation. Fifty-four patients (83.1%) achieved antegrade ejaculation with a median postoperative interval of 3 months (range: 1–10 months). Twenty-eight patients (28/30: 93.3%) and 26 patients (26/35: 74.3%) undergoing bilateral and unilateral nerve-sparing RPLND had antegrade ejaculation, respectively ( P  = 0.041). Only two patients (2.6%) had mediastinal and retroperitoneal recurrences during a median follow-up of 42 months (range: 1–138 months), respectively. However, these patients were cured by chemotherapy and surgery.
Conclusions:   Post-chemotherapy nerve-sparing RPLND preserves ejaculatory function in the majority of patients with advanced GCT without increasing the risk of local recurrence.     

Extensor retinaculum of the wrist: gross anatomical correlation with MR imaging after ultrasound-guided tenography with emphasis on anatomical features in wrist dorsiflexion responsible for tendon impingement

Objective

To demonstrate the anatomy of the extensor retinaculum (ER) of the wrist using gross anatomical correlation with magnetic resonance (MR) imaging before and after ultrasound-guided tenography in four different positions, emphasizing the morphological appearance of the ER that occurs with dorsiflexion of the wrist to define the nature of extensor tendon impingement in athletes who perform repetitive wrist dorsiflexion.

Materials and methods

Institutional policies were followed regarding cadaver use. Ten upper extremities were harvested from fresh cadavers. MR imaging before and after ultrasound-guided tenography of the wrist was performed, followed by gross anatomical correlation. Two radiologists interpreted the MR images and sections by consensus for the anatomical landmarks of the ER, and morphological changes occurring during dorsiflexion of the wrist were analyzed and measured.

Results

The ER of the wrist appeared as a band of low signal intensity on T1- and PD-weighted images. Because of its orientation, axial images were best suited to depict the ER anatomy; specifically, localization of the bony landmarks and the septal attachments. On sagittal images, a consistent appearance of the ER was seen: appearing with fusiform morphology in the neutral position, and becoming shortened and thickened at the abutment point where the extensor tendons of the fourth compartment had a curved excursion during dorsiflexion. The width and thickness of the ER in neutral position averaged 13.56 mm and 1.67 mm respectively. In wrist dorsiflexion, the average width and thickness changed to 8.68 mm and 2.15 mm respectively.

Conclusion

Magnetic resonance imaging is a useful technique to demonstrate the ER of the wrist, the septal attachments, and morphological changes that occur during dorsiflexion of the wrist, which potentially can lead to impingement of the extensor tendons.     

Clinical Effect of Switching from a Luteinizing Hormone-Releasing Hormone Agonist to an Antagonist in Patients with Castration-Resistant Prostate Cancer and Serum Testosterone Level ≥ 20 ng/dl

Introduction

The efficacy of conversion from a luteinizing hormone-releasing hormone agonist to an antagonist was evaluated prospectively in patients with castration-resistant prostate cancer.

Materials and Methods

From October 2012 to December 2014, 8 cases with a serum testosterone level ≥ 20 ng/dl during following androgen deprivation therapy were enrolled and received degarelix monthly. The primary end-pointgoal was to determine the effective prostate-specific antigen response rate. The secondary end-pointgoal was to assess the proportion of cases with a decrease in serum testosterone level to < 20 ng/ml.

Results

One patient achieved a complete response, with a prostate-specific antigen level of 0.02 ng/ml at the nadirend of the study. The effective response rate was 25.0% (2/8), and the proportion of cases with prostate-specific antigen decline was 62.5% (5/8). In 5/8 cases (5/8, 62.5%), serum testosterone levels declined to < 20 ng/dl.

Conclusion

Switching to a luteinizing hormone-releasing hormone antagonist in patients with testosterone levels ≥ 20 ng/dl may be an option in sequential androgen deprivation therapy for some patients.Key Words: Castration-resistant, Degarelix, Prostatic neoplasms, Luteinizing hormone-releasing hormone, Testosterone     

Retroperitoneal lymph node recurrence of seminoma 6 years after high orchiectomy

Late recurrence of stage I testicular seminoma is rare. We herein report a case of retroperitoneal lymph node recurrence of testicular seminoma 6 years after high orchiectomy. A 39-year-old man had a left high orchiectomy for stage I testicular tumor in November 1997. Histopathological findings revealed seminoma (pT3). In 2003, follow up computed tomography showed retroperitoneal lymph nodes swelling. Serum tumor markers had been normal since 1997. Retroperitoneal lymph nodes were dissected in April 2004. Histopathological findings were recurrence of seminoma.     

Salvage radiotherapy for pT3 prostate cancer with PSA failure after radical prostatectomy

We assessed the effectiveness of salvage radiotherapy in 13 patients at pathologic stage T3 (pT3) with prostate specific antigen (PSA) failure after radical prostatectomy: 9 patients at pT3a and 4 patients at pT3b. Three-dimensional dynamic conformal radiotherapy was used for all patients in this study, and the median radiation dose was 57.7 Gy (range, 44-70 Gy) in daily amounts of 2 Gy. The median follow-up after salvage radiotherapy was 643 days (range, 193-1562 days). In 12 of the 13 patients, PSA levels decreased after salvage radiotherapy, but in 1 patient, the PSA level increased and hence the treatment was discontinued at 44 Gy. However, 10 patients exhibited a lasting PSA response. The 3-year biochemical progression-free rate was 74%, and no serious acute or late toxicity was observed during the follow-up. Salvage radiotherapy is likely to become one of the effective treatments for the patients at pT3 with PSA failure following radical prostatectomy.     

The Evaluation of Duct-to-mucosal Pancreaticojejunostomy in pancreaticoduodenectomy

This study was conducted to examine the efficacy of duct-to-mucosal pancreaticojejunostomy compared with external stented pancreaticojejunostomy in prevention of several complications, retrospectively. Seventy-six patients with pancreatic head resection (59 male; median age, 60.1 years) underwent pancreaticoduodenectomy at the Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama, Japan, between January 1, 1994, and March 31, 2002. In early postoperative status, the incidence of pancreatic fistula by duct-to-mucosal anastomosis (n = 45) was similar to that by external stent (n = 31); soft pancreas is a risk factor of pancreatic fistula compared with hard pancreas (p < 0.05). During the late postoperative period, however, no patients with duct-to-mucosal anastomosis showed pancreatic duct dilatation by computed tomography (CT). At the same time, 58.8% of patients with external stent followed by CT showed pancreatic duct dilatation (p < 0.01). The duct-to-mucosal anastomosis was more effective pancreaticojejunostomy than the external stent in terms of prevention of pancreatic duct dilatation, and it should be the surgical procedure of choice in pancreaticoduodenectomy.     

Selective transarterial embolization with n-butyl-2-cyanoacrylate for the treatment of arterial hemorrhage after third molar extraction

Introduction

Comprehensive reports concerning selective embolization for arterial bleeding from third molar removal have not been published. We analyzed cases of arterial bleeding from third molar extraction that required transarterial embolization, and we demonstrate representative cases.

Methods

Five consecutive patients (three men and two women, aged 24 to 37 years) who underwent transarterial embolization at our institution were included in this study. Four of them showed postoperative bleeding after lower third molar removal, and one suffered bleeding after upper third molar extraction. The period of time from extraction to embolization varied from 5 h to 5 weeks.

Results

Angiography revealed pseudoaneurysms at the inferior alveolar artery in four cases and at the superior alveolar artery in one case. The pseudoaneurysms were selectively embolized using 25–33 % n-butyl-2-cyanoacrylate (NBCA)–lipiodol. All of the cases showed good results angiographically and clinically. Transit hypoesthesia at the region of the mental nerve was observed in one patient.

Conclusion

Selective transarterial embolization is an effective technique for arterial bleeding from third molar removal when it is difficult to obtain hemostasis by dental procedures. Injection of NBCA can be useful when the alveolar artery is too small to embolize with coils.     

Oxidative metabolism in the myocardium in normal subjects during dobutamine infusion

To assess the biventricular response of the clearance rate of carbon-11 acetate as an index of myocardial oxidative metabolism to increase in work-load, dynamic positron emission tomography was performed at rest and during dobutamine infusion in 14 normal subjects. The clearance rate constant (K_mono) of the left ventricular (LV) myocardium increased during dobutamine infusion (0.112±0.020 min^–1 vs 0.065±0.015 min^–1 at rest) (P<0.001) in proportion to the increase in the pressure-rate product. K_mono in the right ventricular (RV) myocardium also increased (0.080±0.018 min^–1 vs 0.034±0.013 min^–1 at rest) (P<0.001), with an excellent correlation with the LV K_mono (r=0.920). The fact that the increase in RV Kmono during dobutamine infusion was greater (158%±81%) than that in LV Kmono (79%±39%) (P < 0.005) indicates a greater increase in oxidative metabolism in the RV in response to inotropic stimulation in normal subjects. Correspondence to: N. Tamaki     

Tissue factor antisense oligonucleotides prevent renal ischemia-reperfusion injury

BACKGROUND: Tissue factor (TF) expression is induced on macrophages and endothelial cells during the immune response. We designed an antisense (AS) phosphorothioate oligodeoxynucleotide (ODN) to specifically inhibit the expression of rat TF to study the effects of the AS ODN on renal ischemia-reperfusion injury in the rat. METHOD: AS-1 ODN for TF was delivered intravenously to inhibit the expression of TF in endothelial cells. After 8 hr, the right kidney was harvested and the left renal artery and vein were clamped. The kidney was reperfused after 90 min of ischemia, and rats were killed at 0, 1.5, 5, 12, and 24 hr after reperfusion. TF expression was analyzed by immunohistochemical staining using monoclonal antibody. RESULTS: In the untreated ischemic group, 0 of 20 rats survived beyond day 3. However, treatment with AS-1/TF led to 12 of 20 rats surviving beyond day 4. TF was detected on distal tubular epithelial cells, endothelial cells, and blood vessels but not on necrotic and proximal tubular epithelial cells. The necrotic area extended and encompassed nearly all of the ischemic kidney within 12 hr after reperfusion. The necrotic area and the grade of TF staining were more significantly reduced in the AS-1/TF-treated group than in the control group. Furthermore, fluorescein isothiocyanate-labeled AS-1/TF was significantly intense in tubular epithelial cells 8 hr after intravenous administration. CONCLUSIONS: The results indicate that AS-1/TF inhibited the ischemia-reperfusion injury of the kidney. Microcirculatory incompetence resulting from microthrombus may cause the formation and development of necrosis.