Central opioid receptors differentially regulate the nalmefene-induced suppression of ethanol- and saccharin-reinforced behaviors in alcohol-preferring (P) rats.

The exact opioid-sensitive receptors participating in EtOH-seeking behaviors remains unclear. Previous studies have reported higher densities of micro-opioid receptor binding in the nucleus accumbens (NACC) of P relative to NP rats; however, no differences were seen in delta-receptor binding. In contrast to the NACC, substantially lower levels of micro-receptor binding have been observed in the ventral tegmental area (VTA) of both P and NP rats, albeit no line differences have been observed. In the present study, opioid receptors in the NACC, VTA, and hippocampus were evaluated for their capacity to regulate both EtOH- and saccharin-motivated behaviors in the genetically selected alcohol-preferring (P) rat. To accomplish this, nalmefene, an opiate antagonist with preferential binding affinity for the micro-opioid receptor was unilaterally or bilaterally infused during concurrent availability of 1 h daily EtOH (10% v/v) and saccharin (0.025 or 0.050% w/v) solutions. Rats performed under a two-lever fixed ratio (FR) schedule in which four responses on one lever produced the EtOH solution, and four on a second lever produced the saccharin solution. The results demonstrated that when responding maintained by both EtOH and saccharin are matched at basal levels, unilateral (1-60 microg) or bilateral (0.5-10 microg) microinjections of nalmefene into the NACC produced selective dose-dependent reductions on responding maintained by EtOH. Unilateral (40, 60 microg) and bilateral (10 microg) VTA infusions were also observed to selectively reduced EtOH responding; however, greater nalmefene doses were required and the magnitude of suppression on EtOH responding was markedly less compared with the NACC. The greater sensitivity of nalmefene to suppress EtOH responding in the NACC is likely due to the greater number of opioid receptors in the NACC relative to the VTA. Only bilateral infusion of the 40 microg dose in the NACC and VTA suppressed responding maintained by both EtOH and saccharin. In contrast, intrahippocampal infusions dose dependently suppressed EtOH- and saccharin-maintained responding over a range of doses (1-20 microg). The present study provides evidence that nalmefene suppresses EtOH-motivated behaviors via blockade of opioid receptors within the NACC and VTA, and under various dose conditions both reinforcer and neuroanatomical specificity can be observed.     

A Synergistic Effect Between PG490-88 and Tacrolimus Prolongs Renal Allograft Survival in Monkeys

This study was undertaken to determine if PG490-88 and tacrolimus (Tac) act synergistically to prevent renal allograft rejection in monkeys and to explore possible mechanisms of synergy between these agents. MHC-mismatched renal allografts were transplanted into cynomolgus monkeys after bilateral nephrectomy. Recipients were divided into the following groups: (i) no treatment; (ii) PG490-88 (0.03 mg/kg); (iii) Tac (1 mg/kg); (iv) PG490-88 (0.01 mg/kg) + Tac (1 mg/kg) and (v) PG490-88 (0.03 mg/kg) + Tac (1 mg/kg). Through synergy PG490-88 and Tac inhibited anti-CD3/PMA-induced T-cell proliferation and IFN-gamma expression in vitro. Tac monotherapy only marginally prolonged survival (27 +/- 3.2 days), while the combination of PG490-88 and Tac significantly prolonged graft survival to a median of 99 days (PG490-88 at 0.03 mg) and 38.5 days (PG490-88 at 0.01 mg/kg). Prolonged survival correlated with inhibited IgM production as well as reduced T-cell infiltration, IL-2 protein expression and NF-AT/NF-kappaB activity. We conclude that PG490-88 and a subtherapeutic dose of Tac significantly prolong renal allograft survival in monkeys through the synergistic inhibition of T-cell activation and a decrease in IFN-gamma production and NF-AT/NF-kappaB activity.     

IgA nephropathy and polycystic kidney disease

We report a patient with polycystic kidney disease, advanced renal failure, and nephrotic-range proteinuria. Kidney biopsy revealed IgA nephropathy with lesions of focal and segmental glomerular sclerosis. This association had not been previously described and is probably coincidental. This case supports the assumption that the nephrotic-range proteinuria observed in some polycystic patients could be the consequence of another superimposed glomerular disease. This glomerulopathy can worsen the course of azotemia in these patients.     

Histologic evaluation of radiofrequency ablation in renal cancer.

AIM: To report on the histologic evaluation of renal tumors after intraoperative radiofrequency ablation (RFA) performed immediately before surgical nephrectomy. MATERIALS AND METHODS: Ten patients with renal tumors were studied. All tumors were confirmed to be renal cell carcinoma before radio frequency ablation treatment. All specimens were stained with hematoxylin and eosin and nicotinamide adenine dinucleotide (NADH). RESULTS: Mean tumor size was 29 mm (range 14 to 48 mm). Of the 10 tumors 5 were completely devitalized with a treatment margin ranged from 1 to 20mm. One tumor needed two treatment sessions. No complication related to radiofrequency treatment was recorded. CONCLUSIONS: Our data indicate that RFA can completely destroy renal tumors. However, in our study, complete tumor cell death was obtained only in 50% of cases. More studies are needed to ensure that is technique is an effective and reproducible treatment.     

Tics moderate treatment outcome with sertraline but not cognitive-behavior therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: The presence of a comorbid tic disorder may predict a poorer outcome in the acute treatment of pediatric obsessive-compulsive disorder (OCD). METHODS: Using data from the National Institute of Mental Health (NIMH)-funded Pediatric OCD Treatment Study (POTS) that compared cognitive-behavior therapy (CBT), medical management with sertraline (SER), and the combination of CBT and SER (COMB), to pill placebo (PBO) in children and adolescents with OCD, we asked whether the presence of a comorbid tic disorder influenced symptom reduction on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) after 12 weeks of treatment. RESULTS: Fifteen percent (17 of 112) of patients exhibited a comorbid tic disorder. In patients without tics, results replicated previously published intent-to-treat outcomes: COMB > CBT > SER > PBO. In patients with a comorbid tic disorder, SER did not differ from PBO, while COMB remained superior to CBT and CBT remained superior to PBO. CONCLUSIONS: In contrast to CBT outcomes, which are not differentially impacted, tic disorders appear to adversely impact the outcome of medication management of pediatric OCD. Children and adolescents with obsessive-compulsive disorder and a comorbid tic disorder should begin treatment with cognitive-behavior therapy alone or the combination of cognitive-behavior therapy plus a serotonin reuptake inhibitor.     

Infected chronic hematoma mimicking soft tissue neoplasm

A rare case of an infected chronic hematoma in a patient with immunodeficiency syndrome mimicking a soft tissue neoplasm is presented. There are few reported cases of hematogenous infection of chronic hematomas, which be difficult to differentiate from soft tissue neoplasms.     

Cognitive behavioral treatment for young children with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a distressing and functionally impairing disorder that can emerge as early as age 4. Cognitive behavior therapy (CBT) for OCD in youth shows great promise for amelioration of symptoms and associated functional impairment. However, the empirical evidence base for the efficacy of CBT in youth has some significant limitations, particularly as related to treating the very young child with OCD. This report includes a quantitative review of existing child CBT studies to evaluate evidence for the efficacy of CBT for OCD. It identifies gaps in the literature that, when addressed, would enhance the understanding of effective treatment in pediatric OCD. Finally, it presents a proposed research agenda for addressing the unique concerns of the young child with OCD.     

Validation of a screening questionnaire for hip and knee osteoarthritis in old people

Background  

To develop a sensitive and specific screening tool for knee and hip osteoarthritis in the general population of elderly people.