Evidence for a differential opioidergic involvement in the analgesic effect of antidepressants: prediction for efficacy in animal models of neuropathic pain?

BACKGROUND AND PURPOSE

Antidepressants are one of the recommended treatments for neuropathic pain. However, their analgesic action remains unpredictable, and there are no selection criteria for clinical use. Better knowledge of their mechanism of action could help highlight differences underlying their unequal efficacy.

EXPERIMENTAL APPROACH

We compared the activity of a tricyclic antidepressant (clomipramine) with selective 5-HT and noradrenaline reuptake inhibitors (milnacipran and duloxetine) in streptozocin-induced diabetic and chronic constriction nerve injury-induced neuropathic rats, after repeated injections. We looked for an opioidergic mechanism in their action.

KEY RESULTS

Abolition of mechanical hyperalgesia was observed in mononeuropathic rats after five injections of clomipramine (5 mg·kg⁻¹, s.c.) and milnacipran (10 or 20 mg·kg⁻¹, i.p.) and in diabetic rats after clomipramine. An additional antinociceptive effect was obtained with five injections of duloxetine (3 mg·kg⁻¹, i.p.) in both models and milnacipran (10 mg·kg⁻¹, i.p.) in diabetic rats. These effects were observed with plasma antidepressant concentrations similar to those found in patients treated for neuropathic pain. Naloxone (1 mg·kg⁻¹, i.v.) only suppressed the anti-hyperalgesic effects of clomipramine in both models of pain and of milnacipran in the traumatic model.

CONCLUSIONS AND IMPLICATIONS

The opioid system appears to be involved in the mechanism of action of antidepressants that only have an anti-hyperalgesic effect but not in those that have a stronger (i.e. antinociceptive) effect. These differences between the antidepressants occurred whatever the aetiology of the neuropathy and, if confirmed in clinical trials, could be used to decide which antidepressant is administered to a patient with neuropathic pain.     

Automatic and visual reproducibility of perfusion and function measures for myocardial perfusion SPECT

Background  

We define the repeatability coefficients (RC) of key quantitative and visual perfusion and function parameters that can be derived by the QGS/QPS automated software and by expert visual observer from gated myocardial perfusion SPECT (MPS) scans.     

Adhérences postopératoires et leur prévention en chirurgie gynécologique : I. Ce qu’il faut savoir

Adhesions are the most frequent complications of abdominopelvic surgery, causing important short- and long-term problems, including infertility, chronic pelvic pain and a lifetime risk of small bowel obstruction. They also complicate future surgery with increased morbidity and mortality risk. They pose serious quality of life issues for many patients with associated social and healthcare costs. Despite advances in surgical techniques, including laparoscopy, the healthcare burden of adhesion-related complications has not changed in recent years. Adhesiolysis remains the main treatment although adhesions reform in many patients. The extent of the problem of adhesions has been underestimated by surgeons and the health authorities. There is rising evidence however that surgeons can take important steps to reduce the impact of adhesions. As well as improvements in surgical technique, developments in adhesion-reduction strategies and new agents offer a realistic possibility of reducing adhesion formation and improving outcomes for patients. This paper is the first of a two-part publication providing a comprehensive overview of the evidence on adhesions to allow gynaecological surgeons to be best informed on adhesions, their development, impact on patients, health systems and surgical outcomes. In the second paper we review the various strategies to reduce the impact of adhesions and improve surgical outcomes to assist fellow surgeons in France to consider the adoption of adhesion reduction strategies in their own practice.     

Incidence,Diagnosis, and Treatment of Cardiac Toxicity From Trastuzumab in Patients With Breast Cancer

Purpose of Review

Treatment with trastuzumab is a cornerstone of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer treatment, but carries an unfortunate risk of toxicity to the cardiovascular system. Here, we review recent findings on trastuzumab-associated cardiotoxicity, focusing on its incidence, diagnosis, and treatment.

Recent Findings

Screening with multigated acquisition scan (MUGA) or echocardiogram (ECHO) is recommended to assess cardiac function prior to and during trastuzumab therapy. Because trastuzumab-induced cardiotoxicity is typically reversible, cessation of trastuzumab and/or administration of first-line heart failure agents effectively restores cardiac function in most cases. Severe trastuzumab-induced cardiotoxicity is rare enough that the risk-benefit ratio still weighs in favor of its use in the vast majority of patients with HER2+ breast cancer.

Summary

An improved understanding of the pathophysiology underlying trastuzumab-induced cardiotoxicity and the identification of patients at highest risk will allow us to continue to safely administer trastuzumab in patients with breast cancer.

     

Incremental diagnostic benefit of resolution recovery software in patients with equivocal myocardial perfusion single-photon emission computed tomography (SPECT)

Background

Though myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) is an established diagnostic method, equivocal studies are commonly encountered. New software has been introduced that incorporates resolution recovery (RR) and noise regulation into the reconstruction algorithm and has been used to facilitate “half-dose” and “half-time” studies. Its utility with “full-time, full-dose” acquisition has not been well studied.

Objective

We sought to understand the potential benefit of incorporating RR software in equivocal SPECT studies.

Methods

Patients with full-time, full-dose SPECT MPI were reviewed and those with equivocal results, who subsequently underwent cardiac Rb-82 positron emission tomography (PET) scan were identified. Image reconstruction was performed with iterative reconstruction (IR), attenuation correction (IR + AC), and RR software (IR + AC + RR). Images were anonymized and read blindly by consensus of two experienced readers. All images were qualitatively assessed and semi-quantitatively graded using summed stress and summed rest scores.

Results

45 patients were included (28 males, age = 59.6 ± 9.9 years) and the diagnostic accuracy of each of the reconstruction algorithms (IR, IR + AC, IR + AC + RR) was compared to Rb-82 PET. Agreement of clinical diagnosis of each SPECT reconstruction with Rb-PET showed incremental improvement. The agreement with PET for IR + AC + RR (κ = 0.66, CI 0.454-0.875) is significantly better than for IR (κ = 0.22, CI 0.0-0.450, P = .005) and for IR + AC (κ = 0.32, CI 0.077-0.563, P = .03). Also, IR + AC + RR improved the clinical diagnosis in 14 cases and with overall improvement of reclassification proportion of 23.5% compared to IR (P = .01). Using PET as a reference standard, ROC curves were created for IR + AC + RR, IR + AC, and IR which showed incremental value of the area under the curve of IR + AC + RR (AUC: 0.87; CI 0.76-0.98) over IR + AC (AUC: 0.75; CI 0.61-0.89, P = .078), and over IR (AUC 0.68; CI 0.52-0.84, P = .025).

Conclusion

The addition of RR may help in the diagnosis of patients with equivocal SPECT MPI without the need for additional testing. Further prospective studies are needed to define the role of this new software.     

Adnexal torsion after laparoscopic hysterectomy: description of seven cases

STUDY OBJECTIVE: To discover the prevalence of adnexal torsion after laparoscopic hysterectomy. DESIGN: Retrospective analysis (Canadian Task Force classification II-3). SETTING: A tertiary referral hospital. PATIENTS: One thousand thirty-three women underwent laparoscopic hysterectomies between the years 1995 and 2002. The mean age (+/- SD) of the women at the time of hysterectomy was 43.87 +/- 4.28 years. Intervention. Laparoscopic hysterectomy in which at least one adnexa was left intact. MEASUREMENTS AND MAIN RESULTS: The files of all women with adnexal torsion diagnosed by laparoscopy from 1995 to 2003 were retrospectively reviewed. In seven women, adnexal torsion occurred after laparoscopic hysterectomy. Torsion occurred 2.64 (+/- 1.79) years (mean +/- SD) after hysterectomy. Torsion was treated by laparoscopy in all of the women; either oophorectomy or detorsion and ovariopexy was performed. We calculated the prevalence of this complication to be 7.91/1000. CONCLUSION: Adnexal torsion can occur after laparoscopic hysterectomy.     

Total laparoscopic hysterectomy for very enlarged uteri

STUDY OBJECTIVE: To evaluate short-term outcome of total laparoscopic hysterectomy (TLH) performed in women with very enlarged uteri. DESIGN: Case control study (Canadian Task Force classification II-2). SETTING: Hospital gynecologic service. PATIENTS: Thirty-four consecutive women with very enlarged uteri. INTERVENTION: Total laparoscopic hysterectomy for benign pathology. MEASUREMENTS AND MAIN RESULTS: Women with uterine enlargement (group 1) were compared with 68 women with uteri weighing 300 g or less (group 2) who underwent TLH during the same period. Matching was based on patient age +/- 2 years, surgeon (experienced senior, fellow), whether or not Burch operation was performed, and whether or not adnexectomy was performed. The groups were compared for complication rates, operating time, hospital stay, change in perioperative hemoglobin concentration, and vaginal and laparoscopic uterine morcellation. They did not differ statistically significantly in terms of indications for surgery, parity, postmenopausal status, and preoperative hemoglobin levels. No difference was seen in complication rates between groups. Operating time was significantly shorter (p <0.001) in women with smaller uteri than in those with very enlarged uteri, 108 +/- 35 and 156 +/- 50 minutes, respectively. The groups did not differ significantly in day 1 hemoglobin level drop, analgesia requirement (oral, intravenous opioid), time to passing gas and stool, or hospital stay. No conversion to laparotomy was required in either group. CONCLUSION: A very enlarged uterus should not be considered a contraindication for TLH. However, it may be necessary to undertake certain surgical steps to ensure optimal exposure of the operative field and more effective and safer excision of the uterine vascular pedicle.