Attenuation of the protein wasting associated with bed rest by branched-chain amino acids.

Bed rest is generally accepted as being an appropriate ground-based model for human spaceflight. The objectives of this study were to test the hypothesis that increasing the amount of branched-chain amino acids (BCAAs) in the diet could attenuate the protein loss associated with bed rest. Nineteen healthy subjects were randomized into two groups according to diet. During the 6 d of bed rest, the diets were supplemented with either 30 mmol/d each of three non-essential amino acids, glycine, serine, and alanine (control group), or with 30 mmol/d each of the BCAAs, leucine, isoleucine, and valine (BCAA group). Nutrition was supplied as a commercially available defined formula diet at a rate of 1.3 x REE. Nitrogen (N) balance and urinary 3-MeH excretion were determined for the 6 d. In our results, the urine-based estimate of N balance was 22.2 +/- 14.4 (n = 9) mg N.kg-1.d-1 and 60.5 +/- 10.1 mg (n = 8) N.kg-1.d-1 for the control and BCAA-supplemented groups, respectively (P < 0.05). Urinary 3-MeH excretion was unchanged in both groups with bed rest. We conclude that BCAA supplementation attenuates the N loss during short-term bed rest.     

The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans: a preliminary report

STUDY DESIGN: A prospective randomized controlled human clinical pilot trial. OBJECTIVES: To determine the feasibility of using rhBMP-2/collagen as a substitute for autogenous bone graft inside interbody fusion cages to achieve arthrodesis in humans. SUMMARY OF BACKGROUND DATA: Preclinical studies have shown rhBMP-2 to be an effective substitute for autogenous bone graft, but there are no studies to date documenting such efficacy for human spine fusion. METHODS: Fourteen patients with single-level lumbar degenerative disc disease refractory to nonoperative management were randomized to receive lumbar interbody arthrodesis with a tapered cylindrical threaded fusion cage filled with rhBMP-2/collagen sponge or autogenous iliac crest bone. Patients were evaluated with radiographs, sagittally reformatted computed tomography scans, and Short Form-36 and Oswestry outcome questionnaires. RESULTS: All 11 patients who received rhBMP-2 were judged by three independent radiologists to have solid fusions (at 6, 12, and 24 months postimplantation), whereas only 2 of the 3 control patients, who received the standard treatment of autogenous iliac crest bone, were deemed to be fused. The Oswestry Disability Questionnaire scores of the rhBMP-2 group improved sooner (after 3 months) than those of the autograft group, with both groups demonstrating similar improvement at 6 months. Short Form 36 scores continued to improve up to 24 months. CONCLUSION: The arthrodesis was found to occur more reliably in patients treated with rhBMP-2-filled fusion cages than in controls treated with autogenous bone graft, although the sample size was limited. There were no adverse events related to the rhBMP-2 treatment. This study is one of the first to show consistent and unequivocal osteoinduction by a recombinant growth factor in-humans.     

Mechanisms of anterior cruciate ligament injury

This study examined the mechanisms of anterior cruciate ligament (ACL) injury. In the first part of the study, using a comprehensive, standardized questionnaire, 89 athletes (100 knees) were interviewed about the events surrounding their ACL injury. A noncontact mechanism was reported in 71 (72%) knees and a contact injury in 28 (28%) knees; one patient was unsure if there was any contact. Most of the injuries were sustained at footstrike with the knee close to full extension. Noncontact mechanisms were classified as sudden deceleration prior to a change of direction or landing motion, while contact injuries occurred as a result of valgus collapse of the knee. Hamstring flexibility parameters revealed a statistically higher level of laxity in the injured athletes compared with a matched group of 28 controls. In the second part of the study, videotapes of 27 separate ACL disruptions were reviewed and confirmed that most noncontact injuries occur with the knee close to extension during a sharp deceleration or landing maneuver. Because the knee is in a position to allow the extensor mechanism to strain the ACL and maximum, eccentric muscle force conditions usually apply, the quadriceps may play an important role in ACL disruption. Passive protection of the ACL by the hamstring muscles may be reduced in patients with above-average flexibility.     

Clearance of yttrium-90-labelled anti-tumour antibodies with antibodies raised against the 12N4 DOTA macrocycle.

Radioimmunotherapy (RIT) is currently limited by toxicity to normal tissues as a result of prolonged circulating radioantibody in the blood. In this study, the use of a clearing antibody was investigated (second antibody) in an attempt to reduce blood background levels of [90Y]A5B7 immunoglobulin G (IgG) activity, and, therefore, improve the therapeutic tumour-blood ratio in nude mice bearing human colorectal tumour xenografts. The second antibody was raised against the 12N4 macrocycle group used for chelation of 90Y, and is, thus, applicable to any anti-tumour antibody labelled with this methodology. Second antibody was administered 18, 24 or 48 h after radiolabelled antibody injection and produced up to a tenfold reduction in blood levels and a tenfold improvement in tumour-blood ratios. This has the advantage of reducing the risk of myelotoxicity caused by prolonged retention of activity in the blood. For all normal tissues, there was a similar or slightly lower uptake of [90Y]IgG with second antibody clearance, apart from a transient rise in liver activity due to complexes of primary and secondary antibody clearing via the liver. As a result of clearance of [90Y]IgG from the blood pool, there was an associated fall in the amount of antibody at the tumour site (up to 3.3-fold) at later time points for mice injected with second antibody. However, despite this, tumour-blood ratios remained superior to the control group at these later time points. Estimated dosimetry evaluation revealed that total dose to normal tissues, blood and tumour was lower than for the non-clearance group. Surprisingly, however, there was little improvement in total estimated tumour-blood dose ratio over the time period studied. This was probably because the majority of the dose was delivered to both the blood and tumour within the first 24 h after administration of [90Y]IgG, so that giving the clearing agent after this time did not produce a large difference in total estimated dose. The anti-macrocycle second antibody proved to be a successful clearing agent and could potentially be applied to any anti-tumour antibody coupled with the 12N4 macrocycle. In the light of the estimated dosimetry results described here, it would probably be most useful given at earlier time points (i.e. before 18 h after injection of primary antibody) to produce an improved tumour-blood ratio of total dose. Development of this strategy may allow higher levels of activity to be administered for RIT, and repeated dosing regimens.     

The role of regional anaesthesia and multimodal analgesia in the prevention of chronic postoperative pain: a narrative review

Effective prevention of chronic postoperative pain is an important clinical goal, informed by a growing body of studies. Peri-operative regional anaesthesia remains one of the most important tools in the multimodal analgesic toolbox, blocking injury-induced activation and sensitisation of both the peripheral and central nervous system. We review the definition and taxonomy of chronic postoperative pain, its mechanistic basis and the most recent evidence for the preventative potential of multimodal analgesia, with a special focus on regional anaesthesia. While regional anaesthesia targets several important aspects of the mechanistic pathway leading to chronic postoperative pain, evidence for its efficacy is still mixed, possibly owing to the heterogeneity of risk profiles within the surgical patient, but also to variation in techniques and medications reported in the literature.     

Poor sleep quality as a risk factor for lapse following a cannabis quit attempt

Treatments for cannabis dependence are associated with high rates of lapse/relapse, underscoring the importance of identifying malleable risk factors that are associated with quit failure. Whereas research has demonstrated that poor sleep quality following cannabis discontinuation is related to subsequent use, there has yet to be an examination of whether poor sleep quality prior to a quit attempt results in a similar pattern of lapse. The present study addressed this gap by examining the role of pre-quit sleep quality on early lapse to cannabis use following a self-guided quit attempt, among 55 cannabis dependent military veterans. Results indicated that participants who experienced poor pre-quit sleep quality had greater risk for lapse within the first 2 days (out of 7) following their quit attempt. Findings are discussed in terms of improving treatments for individuals who report poor sleep quality prior to a cannabis quit attempt.