Enamine/enolate-mediated organocatalytic azide-carbonyl [3+2] cycloaddition reactions for the synthesis of densely functionalized 1,2,3-triazoles.

Organocatalytic click! Recent advances in the metal-free enamine/enolate-mediated azide-carbonyl [3+2] cycloaddition reaction are discussed. These approaches require neither a metal catalyst nor alkyne substrates. Owing to the ready availability of carbonyl compounds, these methods thus offer excellent alternatives for the synthesis of 1,4-/1,5-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles.

Fixation of first metatarsal basal osteotomy using Acutrak screw.

BACKGROUND: The purpose of this study is to determine clinical and radiological outcome following the internal fixation of first metatarsal basal osteotomy using Acutrak screw. METHODS: Between May 1999 and December 2003, 37 feet undergoing basal closing wedge osteotomy were stabilised using Acutrak screw. The minimum follow-up period was 18 months. The position and fate of the screw, complications, hallux valgus, intermetatarsal and metatarsal declination angles, and time for bony union were assessed postoperatively and at the final follow-up. RESULTS: Seventy-nine percent of the corrected feet had achieved excellent or good AOFAS score, 13% fair, and 8% poor score. The average preoperative intermetatarsal, hallux valgus and first metatarsal declination angles were 17.3 degrees (12-20 degrees), 38 degrees (17-53 degrees) and 22.5 degrees (16-30 degrees), respectively. These were reduced to 10.3 degrees (0-16 degrees), 14.6 degrees (9-26 degrees) and 20.4 degrees (16-26 degrees) following surgery and 11.2 degrees (0-18 degrees), 16.0 degrees (12-22 degrees) and 20.1 degrees (16-23 degrees), respectively, at the final follow-up. Clinical and radiological union has been achieved in all cases. CONCLUSION: Our technique provides stable fixation with minimal loss of position at the osteotomy site.

Biomechanical testing of the fractured distal radius treated with a new bone cement--is it strong enough?

This study evaluates the in vitro ability of CAP, a bone graft substitute with osteointegration and osteoconductive properties, to restore the anatomy and strength of fractured distal radii. Ten pairs of cadaveric radii were imaged and tested to failure, simulating a fracture. The radii were reconstructed using CAP and were re-fractured and sequentially imaged. The deformities of the bones were determined through computerised evaluation of the radiographs. Radiographic analysis showed that CAP is capable of restoring the anatomy of the distal radius. The load and work required to fracture intact radii were compared to those required to fracture the reconstructed radii. The load to fracture was similar in the two situations. The work to fracture, however, was higher with reconstructed radii, suggesting that these are stronger than the original bones. Our study supports the hypothesis that CAP is capable of restoring the original anatomy and dimensions of the distal radius and re-establishing its mechanical strength.

Total hip replacement for neck of femur fracture: Comparing outcomes with matched elective cohort.

INTRODUCTION: Current literature suggests that total hip replacement (THR) is superior to hemiarthroplasty (HA) for neck of femur fracture in selected group of patients. The outcomes of THR undertaken for trauma setting remain unclear when comparing with elective THR. We compared the outcomes of THR trauma cohort with best-matched elective cohort. METHODS: We retrospectively reviewed 102 patients that underwent THR due to trauma from 2011 to 2013. We had access to 90 cases with complete records. Another 90 matched elective cases were obtained from local arthroplasty database. The elective cases were matched for gender, surgical approaches, surgeon's grade, types of implant, patient's age at operation date of ±5 years and operation date of ±60days. Subsequently, the selection criteria were relaxed to patient's age at operation date of ±10 years and operation date of ±60days. Unmatched cases were excluded. Complications and death rate were compared. RESULTS: The average age for both cohorts was 70 years. The trauma cohort had statistically significant lower BMI and longer hospital stay (p=0.001). The Functional Comorbidity Index (FCI) and Charlson Age Comorbidity Index (CACI) were the same for both cohorts, reflecting an active patient selection for THR in our centre. The trauma cohort had higher surgical complication rate (9% vs 4%), particularly higher dislocation rate (7% vs 1%); and higher medical complication rate (32% vs 6%). These were consistent with the literature. Contrary to literature, the trauma cohort had six dislocations that five of them were done via anterolateral approach. Among the eight trauma cases with surgical complications, six cases were performed by trainees. The cause of surgical complications remains unclear due to the nature of retrospective study. The trauma cohort had higher death rate than the elective cohort (14% vs 4%), with one post-operative cardiac arrest in the trauma cohort. The rest were non-orthopaedic related deaths, ranging between four months to four years. CONCLUSION: A more robust way of selecting trauma patients for THR is warranted to reduce morbidity and mortality. Follow-up for the trauma cohort is warranted, as the patients are likely to outlive the implants.

Blockade of sensitization to methylphenidate by MK-801: partial dissociation from motor effects.

The role of MK-801's locomotor effect in blocking the development of sensitization to methylphenidate was investigated utilizing a computerized locomotor activity monitoring system. After 7 days of acclimation to a 12:12 light-dark cycle (lights on at 07:00), male Sprague-Dawley rats (n=62) were housed in test cages and motor activity was recorded continuously for 16 days. The first 2 days of recording served as a baseline for each rat, and on day 3 each rat received a saline injection. On days 4 to 9 rats were randomly divided into seven groups: Rats received either six daily s.c. injections of methylphenidate (2.5 mg/kg; Group 1), or six daily i.p. injections of 0.30 mg/kg, 0.05 mg/kg MK-801 (Groups 2 and 3, respectively); two MK-801 pre-treatment groups received a single i.p. injection of 0.05, or 0.30 mg/kg MK-801 one hour prior to 2.5 mg/kg methylphenidate (n=8 each) on day 4 followed by five daily injections of 2.5 mg/kg methylphenidate; and finally, two cotreatment groups received a challenge dose of 2.5 mg/kg methylphenidate on day 4 followed by either 0.05 or 0.30 mg/kg MK-801 i.p. one hour prior to 2.5 mg/kg methylphenidate from days 5 to 9. All groups were allowed five days of no treatment before being re-challenged on day 15 with the same treatment they received on day 4. Methylphenidate and 0.30 mg/kg MK-801 sensitized to their own locomotor effects, but 0.05 mg/kg MK-801, which had no acute motor effects, did not. The administration of MK-801 (0.30 mg/kg) prior to methylphenidate either singly on day 4, or coadministered throughout the repeated methylphenidate treatment phase, blocked the development of sensitization to methylphenidate. However, MK-801 at 0.05 mg/kg delayed the development of sensitization when co-administered on days 5 to 9, but a single injection 1 h prior to methylphenidate on day 4 did not prevent sensitization to subsequent methylphenidate administration. In conclusion, MK-801 prevents sensitization to methylphenidate; motor stimulation by MK-801 is not necessary for short-term prevention or delay of sensitization to methylphenidate but may be necessary for a persistent blockade of sensitization.

Dose-related effects of MK-801 on acute and chronic methylphenidate administration.

The non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 has been shown to modulate both the effects of stimulants, such as amphetamine and cocaine, in producing locomotion and the chronic effects of stimulants in producing sensitization. In this study, we examine the interactions between MK-801 and the stimulant methylphenidate. Three different doses of MK-801 were administered 60 min prior to methylphenidate injection (2.5 mg/kg) and the acute response to MK-801 alone and the coadministration with methylphenidate were characterized. MK-801 alone was found to produce dose-dependent locomotor activation. The 0.15 mg/kg dose of MK-801 had no effect on the response to methylphenidate, while the 0. 3 and 0.6 mg/kg doses augmented the methylphenidate response. The effect of pretreatment with MK-801 on subsequent repeated methylphenidate administration was assessed. For all three doses tested, MK-801 pretreatment blocked the progressive locomotor sensitization expected during repeated methylphenidate administration. These findings suggest that MK-801 may exert a long-lasting effect on learning and memory process that result in a blocking of the development of sensitization.

Opportunistic screening for Chlamydia trachomatis in men attending three different secondary healthcare settings.

OBJECTIVES: To assess the feasibility and acceptability of opportunistic Chlamydia trachomatis (CT) screening of asymptomatic men attending three different secondary healthcare settings and to investigate CT positivity in these settings. METHODS: Men attending fracture, fertility and family planning (FP) clinics were invited to be screened by first-void urine and complete a questionnaire which collected demographic, sexual and behavioural characteristics, and their opinion about the screening process. RESULTS: 1290 men were approached, with 80% participating. The number of men approached, number providing a satisfactory urine specimen and CT positivity rate (95% CI) were, respectively, n = 401, n = 206, 14.6% (10.4 to 20.1) for the FP clinic, n = 505, n = 328, 1.2% (0.5 to 3.2) for the fracture clinic and n = 384, n = 319, 0.3% (0.1 to 1.8) for the fertility clinic. The highest rates of CT infection were found in men attending the FP clinics, aged between 20-24 years. Most of the men from all three clinics felt that the setting (87.9%) and specimen (97.7%) were acceptable. CONCLUSION: Opportunistic chlamydial screening of asymptomatic men in three secondary healthcare settings found high positivity rates, but low uptake rates in a FP setting compared with fertility and fracture clinics. Innovative and targeted intervention strategies are required to engage this high-risk group of men in screening.

A prospective double-blind randomised controlled trial of intraoperative pelvic instillation with bupivacaine for management of pain following laparoscopy and dye.

The aim of this randomised, double-blind, placebo-controlled trial was to evaluate the effectiveness of intraperitoneal instillation of bupivacaine following laparoscopy and dye test. Women received either 15 ml of 0.9% saline (n= 42) or 15 ml of 0.5% bupivacaine (n= 43), which was instilled intraperitoneally. Pain and nausea scores were recorded on a visual analogue scale (VAS). Pain perception was no different in the bupivacaine group compared with the control group with median values of VAS at 2 hours (18, 19; P= 0.8), 6 hours (21, 22; P= 0.5), 12 hours (19, 25; P= 0.8), 24 hours (27, 27; P= 0.9) and 48 hours (21, 13; P= 0.26). Women in the bupivacaine group were less nauseated than controls in the immediate postoperative period (with median VAS scores of 0, 8; P value = 0.03 at 2 hours and 0, 7; P= 0.01 at 6 hours).

The role of MK-801 in sensitization to stimulants.

Behavioral responses to stimulants can be progressively and persistently enhanced by their repeated administration. This phenomenon, called behavioral sensitization, may underlie substance abuse, psychosis, recurrence in bipolar disorder, or other psychiatric problems. A growing body of work has implicated excitatory amino acid systems in behavioral sensitization. Most of the evidence for a role of excitatory amino acids has come from experiments demonstrating prevention of sensitization by excitatory amino acid antagonists, especially the noncompetitive NMDA receptor antagonist MK-801. Results of studies with MK-801 have varied, however, leading to conflicting interpretations of its relationship to behavioral sensitization. This paper critically discusses the design of experiments that have used MK-801, and interprets data from these experiments in terms of the two leading explanations for the role of MK-801: 1) that sensitization is an example of the family of plastic events that require excitatory amino acid transmission or 2) that interoceptive cues associated with MK-801 lead to state-dependent learning that modifies sensitization because, in essence, the animal does not recognize the stimulant as the same drug if it is given in close association with MK-801. Based on conflicting reports on effects of MK-801, we propose 1) strategies for distinguishing components of MK-801's effects on responses to stimulants, 2) a model that is a hybrid of the two interpretations of its effects on sensitization, and 3) experimental strategies for testing this model.