Disruption of morphine‐conditioned place preference by a δ2‐opioid receptor antagonist: study of μ‐opioid and δ‐opioid receptor expression at the synapse

The addictive properties of morphine limit its clinical use. Learned associations that develop between the abused opiate and the environment in which it is consumed are engendered through Pavlovian conditioning processes. Disruption of the learned associations between the opiate and environmental cues may be a therapeutic approach to prevent morphine dependence. Although a role for the δ‐opioid receptor in the regulation of the rewarding properties of morphine has already been shown, in this study we further characterized the role of the δ‐opioid receptor in morphine‐induced conditioned responses by examining the effect of a selective δ2‐opioid receptor antagonist (naltriben), using a conditioned place preference paradigm in rats. Additionally, we used a subcellular fractionation technique to analyze the synaptic localization of μ‐opioid and δ‐opioid receptors in the hippocampus, in order to examine the molecular mechanisms that may underlie this morphine‐induced conditioned behavior. Our data show that the administration of 1 mg/kg naltriben (but not 0.1 mg/kg) prior to morphine was able to block morphine‐induced conditioned place preference. Interestingly, this naltriben‐induced disruption of morphine conditioned place preference was associated with a significant increase in the expression of the δ‐opioid receptor dimer at the postsynaptic density. In addition, we also observed that morphine conditioned place preference was associated with an increase in the expression of the μ‐opoid receptor in the total homogenate. Overall, these results suggest that modulation of the δ‐opioid receptor expression and its synaptic localization may constitute a viable therapeutic approach to disrupt morphine‐induced conditioned responses.     

Differential effects of a unilateral hypothalamic lesion on ovulation and compensatory ovarian hypertrophy in hemiovariectomized adult rats

The effects were analysed of a unilateral lesion in the anterior or medial hypothalamus made on the day of oestrus on right or left hemicastrated rats. On the day of oestrus after two consecutive oestrous cycles of the same length, the ovulation rate in rats with lesions in the anterior left hypothalamus was lower than in control hemicastrated animals (5/16 vs 18/20; P less than 0.01), and normal in those rats with lesions in the right side (14/18). None of the animals with lesions in the left side of the anterior hypothalamus and with the left ovary in situ ovulated (0/7), but 5/9 with the right ovary in situ did ovulate (P less than 0.05). Lesions on either side of the medial hypothalamus did not modify ovulation rate. Compensatory ovulation was reduced in those animals with lesions in the right anterior hypothalamus and with the right ovary in situ. Lesions in either side of the medial hypothalamus reduced compensatory ovulation. Lesions in the right side of the anterior and medial hypothalamus increased compensatory ovarian hypertrophy in the left ovary and decreased it in the right ovary. Lesions in the left side of the anterior hypothalamus increased compensatory ovarian hypertrophy in the left ovary only, whereas lesions in the left side of the medial hypothalamus reduced compensatory ovarian hypertrophy in the right ovary. The results suggest that the information arising in each side of the anterior and medial hypothalamus plays different roles in the ipsi-and contralateral ovary, when either the left or the right ovary is absent.     

Torsion of the cryptorchid testis--can it be salvaged?

PURPOSE: The literature concerning undescended testis mainly concentrates on the increased risks of infertility and development of germ cell tumors. Yet the UDT also appears to be at higher risk for torsion compared to the normally descended testis, and this issue is relatively poorly addressed. We reviewed all cases of torsion of UDTs operated on at our hospital during the last 20 years in an attempt to characterize better this condition and its salvageability. MATERIALS AND METHODS: In this retrospective clinical study we reviewed and analyzed all cases of testicular torsion involving UDT operated on at our hospital between 1984 and 2004. RESULTS: A total of 11 children were operated on at our hospital for torsion of undescended testis between 1984 and 2004. Patient age ranged from 1 month to 18 years (median 7.5 months). In all cases unilateral torsion of undescended testis was diagnosed, with 73% of cases involving the left side. Clinical symptoms included inguinal swelling and erythema associated with a tender, firm mass palpated in the groin area and an empty ipsilateral hemiscrotum. Doppler ultrasound examination was routinely performed in the last 7 patients to confirm the diagnosis. During inguinoscrotal exploration severe ischemia or overt necrosis of the testis was found in 5 of 11 cases. Three of these 5 cases were managed by orchiectomy, while in the other 2 cases the testis subsequently vanished. In the 6 patients who exhibited some improvement following detorsion and warming of the tissue the testes were preserved and orchiopexy was performed. Followup was available in only 5 patients, with vanishing of the torsed testis observed in 4 and a normal testicle detected 21 years postoperatively in 1 patient who was diagnosed early. CONCLUSIONS: This series clearly demonstrates poor rates of surgical salvage, which we mainly attribute to delays in parental response and in primary physician referral to the hospital. Parents, who have a pivotal role in early diagnosis, were usually unaware of this urological emergency, and some were surprisingly unaware of the presence of cryptorchidism. By increasing the awareness regarding this entity among members of the medical community and parents, we hope that torsion of the cryptorchid testis (literally, "hidden testis") will no longer necessarily be synonymous with "crypt-torsion" ("hidden torsion").     

A Novel Non-Invasive Adjuvant Biomechanical Treatment for Patients with Altered Rehabilitation after Total Knee Arthroplasty: Results of a Pilot Investigation

Background

Many factors contribute to suboptimal results after total knee arthroplasty (TKA) but little is known regarding the value of postsurgical rehabilitation after TKA. We examined the effects of an enhanced closed kinematic chain exercises program (AposTherapy) on gait patterns and clinical outcomes among patients with a lack of progress in their postsurgical rehabilitation.

Methods

Twenty-two patients were prospectively followed during the study. Gait spatiotemporal parameters were measured at the initial evaluation, after 15 minutes of therapy, and after 3 months of therapy. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the short form (SF) 36 health survey were completed by patients before treatment and after 3 months of treatment.

Results

The WOMAC and SF-36 scores improved significantly after 3 months of treatment. Gait velocity, single limb support, and step length of the operated leg improved significantly even after a single 15 minutes treatment. Normal gait velocity was observed in 36% of patients after 3 months of treatment.

Conclusions

A physiotherapy program that included enhanced closed kinematic chain biomechanical therapy was beneficial for patients who experienced a suboptimal rehabilitation course after TKA.     

EAU Guidelines on Urethral Trauma

Context

These guidelines were prepared on behalf of the European Association of Urology (EAU) to assist urologists in the management of traumatic urethral injuries.

Objective

To determine the optimal evaluation and management of urethral injuries by review of the world's literature on the subject.

Evidence acquisition

A working group of experts on Urological Trauma was convened to review and summarize the literature concerning the diagnosis and treatment of genitourinary trauma, including urethral trauma. The Urological Trauma guidelines have been based on a review of the literature identified using on-line searches of MEDLINE and other source documents published before 2009. A critical assessment of the findings was made, not involving a formal appraisal of the data. There were few high-powered, randomized, controlled trials in this area and considerable available data was provided by retrospective studies. The Working Group recognizes this limitation.

Evidence synthesis

The full text of these guidelines is available through the EAU Central Office and the EAU website (www.uroweb.org). This article comprises the abridged version of a section of the Urological Trauma guidelines.

Conclusions

Updated and critically reviewed Guidelines on Urethral Trauma are presented. The aim of these guidelines is to provide support to the practicing urologist since urethral injuries carry substantial morbidity. The diversity of urethral injuries, associated injuries, the timing and availability of treatment options as well as their relative rarity contribute to the controversies in the management of urethral trauma.     

Modulation of isolated N-methyl-d-aspartate receptor response under hyperbaric conditions

In humans, hyperbaric pressure induces the high-pressure neurological syndrome (HPNS). HPNS is characterized by tremor, sleep disorders, electroencephalographic changes, and impairment of cognitive and motor performances. In animals, higher pressures result in convulsions and death. An increased N-methyl-d-aspartate receptor (NMDAR) response has been implicated with HPNS. We studied high-pressure effects on pharmacologically isolated NMDAR field excitatory postsynaptic potentials (fEPSPs). Hippocampal coronal brain slices from male Sprague-Dawley rats were prepared, constantly superfused with physiological solutions, gas-saturated at normobaric pressure and compressed up to 10.1 MPa with helium. fEPSPs were recorded from the dendritic layer of CA1 pyramidal neurones. High pressure significantly increased the single fEPSP delay, maximal initial slope, amplitude, decay time and time integral (elevated Na(+) and Ca(2+) influx) despite the known general decrease in glutamatergic synaptic release. The estimated negative and positive activation volumes (DeltaV*) for various kinetic segments of the fEPSP suggest a complex response of the receptor to pressure. The NMDAR frequency response was tested by a train of five stimuli. At 50-100 Hz, high pressure did not increase the fEPSPs' frequency-dependent depression and the train's time integral remained unchanged. At 25 Hz, pressure induced a larger frequency-dependent depression and significantly increased the time integral. Our results provide, for the first time, direct information on the isolated brain NMDAR response under hyperbaric conditions. These observations may explain some increase in the excitability of single normal glutametergic fEPSPs and their frequency responses.     

Targeting Nursing Homes Under the Quality Improvement Organization Program's 9th Statement of Work

In the Quality Improvement Organization (QIO) program's latest Statement of Work, the Centers for Medicare and Medicaid Services (CMS) is targeting its nursing home activities toward facilities that perform poorly on two quality measures—pressure ulcers and restraint use. The designation of target facilities is a shift in strategy for CMS and a direct response to criticism that QIO program resources were not being targeted effectively to facilities or clinical areas that most needed improvement. Using administrative data, this article analyzes implications of using narrowly defined criteria to identify facilities that need improvement, particularly in light of considerable evidence showing that nursing home quality is multidimensional and may change over time. The analyses show that one in four facilities is targeted for improvement nationally but that approximately half of some states' facilities are targeted while other states have almost none targeted. The analyses also convey deeper limitations to using threshold values on individual measures to identify poorly performing homes. Target facilities can be among the top performers on a range of other quality measures, and their performance on targeted measures themselves may change over time. The implication of these features is that a very different group of facilities would have been chosen had the QIO program targeted other measures or examined performance at a different point in time. Ultimately, CMS has chosen a blunt instrument to identify poorly performing nursing homes, and supplemental strategies—such as soliciting input from state survey agencies and more closely aligning quality improvement and quality assurance efforts—should be considered to address potential limitations.     

Atypical antipsychotic use and risk of fracture in persons with Parkinsonism

Our objective was to estimate the effect of atypical antipsychotics (AAs) on the rate of fractures in a parkinsonism population. We conducted an age‐ and state‐matched nested case‐control study in five states (CA, FL, NY, OH, IL) using the Medicaid analytic extract from 2001 to 2002. Eligible participants had a diagnosis of parkinsonism, excluding persons with secondary parkinsonism, bone cancer, bone infections, schizophrenia, schizoaffective disorder, and those who used conventional antipsychotics. The primary outcome was the occurrence of a fracture of the femur, ankle, fibula, tibia, humerus, radius, or ulna (N = 851). Risk‐set sampling defined controls (N = 4220). We used conditional‐logistic regression to derive adjusted odds ratios (AOR) and 95% confidence intervals of the association between fracture and use of quetiapine, risperidone, or olanzapine in the 60 days before the index date compared to nonuse. After adjustment for confounding, use of quetiapine (AOR 2.4; 95% CI 1.5–3.8), risperidone (AOR 1.2; 95% CI 0.9–1.7), or olanzapine (AOR 1.7; 95% CI 1.2–2.4) was associated with a higher rate of fracture. Use of an AA was associated with a higher rate of fracture in persons with parkinsonism. Prescribers must be cautious when using these agents in elderly persons with parkinsonism. © 2009 Movement Disorder Society     

Nitric Oxide-Mediated Toxicity in Paraquat-Exposed SH-SY5Y Cells: A Protective Role of 7-Nitroindazole

The precise mechanism underlying the role of nitric oxide (NO) or nitric oxide synthases (NOSs) in paraquat-mediated toxicity is yet to be fully elucidated. The importance of the NADPH-diaphorase activity of NOSs in paraquat toxicity, in addition to the production of NO, has previously been reported as a mechanism of toxicity. However, other studies have highlighted the toxicity of NO alone and, conversely a protective role of NO in paraquat-mediated toxicity has also been described. The goal of this study was to clarify the involvement of NO and NOS in paraquat-mediated toxicity in an SH-SY5Y cell system, and to evaluate the putative role of 7-nitroindazole as a protective agent in human neural cells. Our results indicate that the three previously described isoforms of NOS are expressed in SH-SY5Y cells, with the data showing that these synthases act as paraquat diaphorases. While this process could occur at the expense of NO production, NO alone does play a toxic role, with its production leading to the formation of the toxicant peroxynitrite. Although the efficacies of the different inhibitors tested cannot be directly compared because the various NOS forms were probably inhibited to differing extents, the results support the idea that endogenous and inducible NO is a neurotoxic mediator of the effects of paraquat. The NADPH-diaphorase activity of NOS and NO production are therefore factors implicated in the toxicity mediated by the herbicide paraquat.