Quantification of 5-HT1A and 5-HT2A receptor Binding in Depressed Suicide Attempters and Non-Attempters

Objective: To determine serotonin system abnormalities related to major depression or previous suicidal behavior.

Methods: [¹¹C]WAY100635, [¹⁸F]altanserin and positron emission tomography were used to compare 5-HT_1A and 5-HT_2A binding in MDD patients divided into eight past suicide attempters (>4yrs prior to scanning) and eight lifetime non-attempters, and both groups were compared to eight healthy volunteers.

Results: The two receptor types differed in binding pattern across brain regions from each other, but there were no differences in binding between healthy volunteers and the two depressed groups or between depressed suicide attempters and non-attempters. No effects of depression severity or lifetime aggression were observed for either receptor.

Conclusion: Limitations of this study include small sample size and absence of high lethality suicide attempts in the depressed attempter group. No trait-like binding correlations with past suicide attempt or current depression were observed. Given the heterogeneity of nonfatal suicidal behavior, a larger sample study emphasizing higher lethality suicide attempts may find the serotonin biological phenotype seen in suicide decedents.     

Revascularized fibula for tibia replacement in adamantinoma

Adamantinoma of long bones is one of the rarest of malignant bone tumors; it is commonly located in the middle or lower third of the diaphysis of the tibia. A case with multiple occurrences affecting both the tibia and fibula is presented. En bloc resection with wide operative margins was performed, and a large tibial defect of 23 cm was effectively bridged by a revascularized free fibular flap. At 13 months follow-up, there was no sign of local recurrence or metastasis, and the patient was mobile.     

Dental trauma that require fixation in a children's hospital.

Children and adolescents who suffer traumatic injuries often seek emergency treatment at a Children's Hospital. Complex injuries to permanent teeth and their periodontium require immediate repositioning and stabilization. Many of these emergencies are treated by pediatric dental residents at the Women and Children's Hospital of Buffalo, Buffalo, New York. The purpose of this study was to characterize these complex injuries of permanent teeth that require emergency treatment in a Children's Hospital. All of the cases of dental trauma which had involved permanent teeth and which had been treated with a splint in 2001 and 2002 were reviewed. There were 79 patients that were between 5 and 19 years of age with twice as many males (54) as females (25). The number of males increased from childhood (5-10 years) to early adolescence (11-15 years) and then decreased rapidly in late adolescence (16-19 years), whereas the number of females decreased steadily with age. Most of the incidents occurred during the summer months (72%), particularly in June and July (42%), and Fridays and Saturdays were the busiest days of the week. Most of the injuries were caused by organized and recreational sporting activities (39%) and accidental falls (33%), followed by interpersonal violence (15%) and a few motor vehicle accidents (7%). The 173 permanent tooth injuries were mostly luxations (62%) or avulsions (20%), with only a few fractures of the alveolar bone (5%) or tooth root (1%). Most of the displacements were lateral luxations (40%) or extrusions (18%) with only a few intrusions (3%). These injuries most commonly afflicted the maxillary central incisors (54%), followed by the maxillary laterals (18%) and mandibular centrals (17%). The emergency treatment that was provided at the Children's Hospital included replantation and repositioning, and the placement of a semi-rigid or flexible splint.     

In VivoStudies of Adenovirus-Based p53 Gene Therapy for Ovarian Cancer

Objectives.To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (ip) 2774 human ovarian cancer cell line that contains a p53 mutation.Study design.An initial study of adenovirus tolerance was determined in nude mice by a single ip injection of increasing doses of Ad-CMV-p53. Nude mice were implanted with an LD₁₀₀dose of 1 × 10⁷cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV-p53 and another group received a control adenovirus construct, Ad-CMV-βgal. To study the treatment response to Ad-CMV-p53, the mice were divided into groups and received various treatment schedules of 1 × 10⁸pfu of Ad-CMV-p53.Results.The mice tolerated Ad-CMV-p53 without adverse effects at doses of 1 × 10⁸pfu. The response to Ad-CMV-p53 showed significant survival duration in each dose regimen, with a survival time greater than that of untreated animals (P= 0.0173). However, no statistically significant survival advantage was observed between Ad-CMV-p53- and Ad-CMV-βgal-treated mice.Conclusions.These studies show that at the adenovirus dose and administration regimen used, there is effective but not specific 2774 tumor growth inhibitionin vivo.Efficient introduction of biologically active genes into tumor cells would greatly facilitate cancer therapy. Thus, although promising, these results caution that much effort will be required to realize the potential for clinical application of adenovirus-based ovarian cancer gene therapy.     

Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial.

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.     

Pressure distribution in the knee joint

Biomechanical factors influencing the patterns of pressure distribution at the articular surface and the subchondral bone are suggested to be most important in the pathogenesis of osteoarthritis and ostechondritis dissecans at the knee joint. Besides this, chronic joint instability is another important factor under discussion in the etiology of osteoarthritis of the knee. The patterns of pressure distribution on the femoral condyles of weight-bearing knee joints were investigated in a biostatic cadaver model. The pressure on the femoral condyles was evaluated using pressure-sensitive films with the knee in different physiological joint positions (extension, 15° and 30° flexion) with and without division of either the medial collateral ligament (MCL), the lateral collateral ligament (LCL), the MCL and the anterior cruciate ligament (ACL), or the LCL and the ACL. Results showed that the location of the contact area and peak pressure depended on the joint position and stage of ligament division. Without ligament division the maximum peak pressure was always observed on the medial condyle. Only after MCL and combined MCL + ACL division did the lateral condyle show in extension a higher peak pressure than the medial condyle. Division of the LCL and LCL + ACL resulted in an increase in peak pressure on the medial condyle, particularly in flexion. The highest peak pressure of all was measured in the 30° flexion position on the medial condyle after division of the LCL. The lowest at all was found on the lateral condyle in 15° flexion after LCL division. Additional ACL division resulted in only minor further changes. These results are important for the interpretation of clinically observed factors discussed in the etiology of secondary osteoarthritis of the knee and contribute to the theory of mechanical induction of osteoarthritis and osteochondritis dissecans.Presented in part at the 21st Congress of the Austrian Society of Orthopedic Surgery; May 5th–June 1st, 1991 in Linz/Austria     

Binding potency of paroxetine analogues for the 5-hydroxytryptamine uptake complex.

The in-vitro inhibition constants (Ki) of 14 structural analogues of the potent 5-hydroxytryptamine (5-HT)-uptake inhibitor paroxetine were determined to assess the structure-affinity relationship of these derivatives. A goal of these studies was to determine those positions on paroxetine which could be derivatized without significantly decreasing the affinity of the drug for the binding site, so that radiolabels such as [18F]fluoroalkyl groups might be appended for future in-vivo imaging studies of the 5-HT uptake system. Using the methyl moiety as a steric probe for these studies, it was found that the rank order of potency of various methyl-substituted paroxetine analogues for inhibiting the binding of [3H]paroxetine to the 5-HT re-uptake site was: 4'-approximately equal to 3'-approximately equal to 2'- > 2'-approximately equal to 1- > 5'- > 6'-methyl. The in-vitro equipotent molar ratios (EPMR, Ki(analogue)/Ki(paroxetine)) of the analogues were determined, and the EPMRs of the 4'-, 3'-, and 2'-methyl derivatives were 1.9, 2.2 and 2.2, respectively. The 4'- and 2'-fluoromethyl and -fluoroethyl analogues were synthesized, and the EPMRs of the 4'- and 2'-fluoromethyl derivatives were determined to be 2.0 and 3.5, and those of the 4'- and 2'-fluoroethyl analogues were 5.2 and 6.2, respectively. The 2'-fluoromethyl analogue was unstable in aqueous solutions, and it is not a promising ligand for in-vivo studies.(ABSTRACT TRUNCATED AT 250 WORDS)