Myonuclear alterations associated with exercise are independent of age in humans.

Age-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with the nuclear lamina protein lamin A regulating nuclear shape, nuclear mechanics and ultimately gene expression. Defective lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than those from untrained individuals. Complementary to this, exercise resulted in increased levels of lamin A and increased myonuclear stiffness in mice. We conclude that exercise is associated with myonuclear remodelling, independently of age, which may contribute to the preservative effects of exercise on muscle function throughout the lifespan. KEY POINTS: The nucleus plays an active role in translating forces into biochemical signals. Myonuclear aberrations in a group of muscular dystrophies called laminopathies suggest that the shape and mechanical properties of myonuclei are important for maintaining muscle function. Here, striking differences are presented in myonuclear shape and mechanics associated with exercise, in both young and old humans. Myonuclei from trained individuals were more spherical, less deformable and contained a thicker nuclear lamina than untrained individuals. It is concluded that exercise is associated with age-independent myonuclear remodelling, which may help to maintain muscle function throughout the lifespan.

Implantable cardioverter defibrillators in octogenarians: clinical outcomes from a single center.

AIMS: Limited data exist on outcomes in very elderly ICD recipients. We describe outcomes in new ICD and Cardiac Resynchronisation Therapy with Defibrillator (CRT-D) implants in octogenarians at our institution. METHODS: Patients aged 80 years and above who underwent de novo ICD or CRT-D implantation from January 2006 to July 2012 were identified. Clinical data were collected from the procedural record, medical and ICD notes. Baseline characteristics were compared using independent sample t test for continuous variables and Fisher's exact test for categorical variables. Kaplan-Meier curves were constructed. RESULTS: Ten per cent of all new ICD/CRT-D implants were aged 80 years and over. Median age was 83.0 years. Median follow-up was 29 months. Death occurred in 17 (34%). Median time to death was 23 months. Three deaths (6%) occurred within 12 months of ICD implantation. Appropriate therapy (ATP or shock) occurred in 19 (38%). Inappropriate therapy occurred in 6 (12%). Rates of appropriate shocks and inappropriate therapy (shocks and ATP) and significant valvular incompetence were higher amongst deceased patients (P=0.03 OR 5.9 95% CI 1.3-27) and (P=0.02 OR 12 95% CI 1.3-112). Univariate analysis identified diuretic use (P=0.008 95% C.I. 0.05 to 0.63) and appropriate shock (P= 0.025 95% C.I. 1.25 to 26.3) as predictors of mortality. CONCLUSION: Octogenarians make up a small but increasing number of ICD recipients. This study highlights high survival rates at one year with acceptable rates of appropriate and inappropriate device therapy. Ongoing debate regarding the appropriateness of ICD in very elderly patients is warranted.

Evaluation of common vaginal tunic ligation during field castration in draught colts.

The objective of this study was to determine if ligation of the common vaginal tunic could prevent or reduce the incidence of omental herniation and eventration in draught colts undergoing routine field castration. It was found that common vaginal tunic ligation, while not completely preventing omental herniation and evisceration, significantly reduced the incidence of these complications and should be considered in those males deemed at increased risk of significant post castration complications.

Surgical repair of femoral fractures in New World camelids: five cases (1996-2003).

Five New World camelids were admitted to the Western College of Veterinary Medicine between 1996 and 2003 for evaluation of femoral fractures. There were three alpacas and two llamas. Four of the animals were female and three were less than 3 months of age. Fracture configurations consisted of distal physeal fractures (three), a comminuted diaphyseal/metaphyseal fracture, and a transverse diaphyseal fracture. Fractures were diagnosed with a combination of physical examination and radiographs in all cases. All five fractures were repaired with internal fixation and three animals were discharged from the hospital with fractures that healed. One cria underwent successful internal fixation but died from pulmonary oedema during recovery from anaesthesia. Postoperative complications were rare and limited to inadequate fracture stability in one alpaca and prolonged recovery to weight bearing in another. One llama with a comminuted metaphyseal fracture, repaired with a 4.5 mm dynamic compression plate, subsequently had catastrophic failure of the bone 17 days after surgery. Overall the clients were pleased with the outcome of discharged animals. Although femoral fractures are considered rare, they pose a unique opportunity for the large animal veterinarian to successfully achieve fracture union with the aid of internal fixation.

'Modern' distal femoral locking plates allow safe, early weight-bearing with a high rate of union and low rate of failure: five-year experience from a United Kingdom major trauma centre.

AIMS: Fractures of the distal femur can be challenging to manage and are on the increase in the elderly osteoporotic population. Management with casting or bracing can unacceptably limit a patient's ability to bear weight, but historically, operative fixation has been associated with a high rate of re-operation. In this study, we describe the outcomes of fixation using modern implants within a strategy of early return to function. PATIENTS AND METHODS: All patients treated at our centre with lateral distal femoral locking plates (LDFLP) between 2009 and 2014 were identified. Fracture classification and operative information including weight-bearing status, rates of union, re-operation, failure of implants and mortality rate, were recorded. RESULTS: A total of 127 fractures were identified in 122 patients. The mean age was 72.8 years (16 to 101) and 92 of the patients (75%) were female. A consultant performed the operation in 85 of the cases, (67%) with the remainder performed under direct consultant supervision. In total 107 patients (84%) were allowed to bear full weight immediately. The rate of clinical and radiological union was 81/85 (95%) and only four fractures of 127 (3%) fractures required re-operation for failure of surgery. The 30-day, three- and 12-month mortality rates were 6 (5%), 17 (15%) and 25 (22%), respectively. CONCLUSION: Our study suggests an exponential increase in the incidence of a fracture of the distal femur with age, analogous to the population suffering from a proximal femoral fracture. Allowing immediate unrestricted weight-bearing after LDFLP fixation in these elderly patients was not associated with failure of fixation. There was a high rate of union and low rate of re-operation. Cite this article: Bone Joint J 2017;99-B:951-7.

ECG predictors of T wave oversensing in subcutaneous implantable cardioverter defibrillators.

BACKGROUND: T wave oversensing (TWOS) is the commonest cause of inappropriate shocks in subcutaneous implantable cardioverter defibrillators (S-ICDs). We hypothesise that predictors of TWOS can be derived from surface ECG parameters. METHODS: In a cohort of SICD recipients in two UK centres, all patients who had TWOS (study group) were compared to all those who had not (control group). The pre-implant screen was scanned and the R wave, T wave amplitudes, QRS interval, time to peak T wave, QT interval and R:T ratio was measured using digital callipers. Logistic regression was performed to identify ECG predictors of TWOS. RESULTS: One hundred one patients were studied. Six (5.9%) had TWOS. The mean age of the population was 58.6±18years and the median follow-up was 19.5months. By univariate analysis, the predictors of TWOS are QRS duration (140.7±28.7 vs. 105.9±24.6, P=0.007), time to peak T wave (corrected for heart rate, pTc) (403.9±22.6 vs. 347.8±41.4, P=0.006), QTc interval (500.4±41.2 vs. 446.8±49.7, P=0.021), and R:T ratio (3.5±1.1 vs. 9.5±13.2, P=0.034). By multivariate analysis, time to pTc is the most predictive of TWOS. A time to pTc of 390ms cut-off point provided a sensitivity 38.5%, a specificity of 98.9%, a positive predictive value for TWOS of 83.3%, and a negative predictive value of 91.6% (AUC=0.687). CONCLUSION: In this study, time to pTc is the most powerful ECG predictor of TWOS.

Systematic review of aspirin for thromboprophylaxis in modern elective total hip and knee arthroplasty.

AIMS: There is uncertainty regarding the optimal means of thromboprophylaxis following total hip and knee arthroplasty (THA, TKA). This systematic review presents the evidence for acetylsalicylic acid (aspirin) as a thromboprophylactic agent in THA and TKA and compares it with other chemoprophylactic agents. MATERIALS AND METHODS: A search of literature published between 2004 and 2014 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 13 studies were eligible for inclusion. RESULTS: Evidence from one good quality randomised controlled trial (RCT) showed no difference in rates of venous thrombo-embolism (VTE) in patients given aspirin or low molecular weight heparin (LMWH) following TKA. There was insufficient evidence from trials with moderate to severe risk of bias being present to suggest aspirin is more or less effective than LMWH, warfarin or dabigatran for the prevention of VTE in TKA or THA. Compared with aspirin, rates of asymptomatic deep vein thrombosis (DVT) in TKA may be reduced with rivaroxaban but insufficient evidence exists to demonstrate an effect on incidence of symptomatic DVT. Compared with aspirin there is evidence of more wound complications following THA and TKA with dabigatran and in TKA with rivaroxaban. Some studies highlighted concerns over bleeding complications and efficacy of aspirin. CONCLUSION: The results suggest aspirin may be considered a suitable alternative to other thromboprophylactic agents following THA and TKA. Further investigation is required to fully evaluate the safety and efficacy of aspirin. Cite this article: Bone Joint J 2016;98-B:1056-61.

Atrial fibrillation and hypertrophic cardiomyopathy: who to anticoagulate?

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac conditions. Atrial fibrillation (AF) has been demonstrated to be the most frequent arrhythmia encountered in HCM patients. Research focusing on AF and embolic stroke in HCM patients has been sparse and the sample size of most studies is small. The prognostic significance of AF in HCM patients is still not well known. The aim of this article is to provide further understanding of the anti-coagulation requirement of HCM patients with AF.

The antinociceptive effects of anterior pretectal stimulation in tests using thermal, mechanical and chemical noxious stimuli.

Four behavioural tests have been used to study the antinociceptive effects of electrical stimulation of the anterior pretectal nucleus (APtN) in the rat. The antinociceptive effects of stimulating this nucleus, which lies dorsally in the posterior diencephalon, have recently been studied extensively but always using briefly applied heat stimuli. It is reported here that APtN stimulation effectively inhibited responses to briefly applied noxious pressure and longer-lasting noxious chemical (formalin) stimuli. Although the tail-flick reflex to noxious heat was very potently depressed by APtN stimulation, responses to noxious heat in the hot-plate test were not. Three doses of morphine were also studied with each test and it was concluded that 15 sec of 35 microA r.m.s. current into the APtN was as effective as 3-5 mg/kg morphine s.c. in the rat.

Antagonism of N-methylaspartate and synaptic responses of neurones in the rat ventrobasal thalamus by ketamine and MK-801.

1. Extracellular single neurone recordings were made in the ventrobasal thalamus of urethane-anaesthetized rats. 2. Iontophoretically and intravenously administered ketamine and MK-801 were found to be selective antagonists of responses of neurones to iontophoretically applied N-methylaspartate. 3. Both antagonists, administered in N-methylaspartate-selective quantities, reduced the synaptic responses of ventrobasal thalamus neurones to a two-second air jet directed at the peripheral receptive field.

A search for lymphatic drainage of the monkey orbit.

Colloid solutions of technetium Tc 99m and india ink injected into the retrobulbar space of the cynomolgus monkey outside the extraocular muscle cone were removed from the orbit by the lymphatic vessels of the conjunctiva and eyelids and were then concentrated within the lymph nodes that drained the conjunctival and eyelid areas. Colloid solutions injected into the retrobulbar space inside the extraocular muscle cone did not reach the conjunctiva and did not collect in any lymph nodes over a 24-hour period. Within the orbit, the injected colloids spread along the planes of the connective-tissue septa. No lymphatic vessels were identified within the orbits posterior to the conjunctiva. Small amounts of india ink left the posterior orbit and ultimately entered the contralateral orbit. This posterior pathway did not lead to lymphatic vessels or lymph nodes and therefore does not appear to represent a prelymphatic pathway.

Absent pulmonary valve syndrome with interrupted aortic arch.

A surgically treated case of absent pulmonary valve syndrome associated with type B interrupted aortic arch is presented. The presence of a restrictive ductus arteriosus promoted the development of a collateral circulation between ascending and descending thoracic aorta, allowing the child to remain clinically stable after birth.

Optimization of signal detection in SPECT.

Parallel-hole collimators of varying design are discussed, using the display signal-to-noise ratio of R.F. Wagner et al. (Med. Phys., vol.6, p.83-94, 1979) to obtain contrast-detail diagrams and analytical expressions for the signal-to-noise ratio in SPECT (single-photon-emission computed tomography). It is concluded: (1) that the detectability of deeply embedded small objects (more than ~10 cm deep) may be improved only slightly by improvements in the resolution and geometric efficiency of parallel-hole collimators; (2) that a long-bore collimator outperforms a low-energy general-purpose collimator for objects smaller than ~2 cm, but only to a minor degree; and (3) that for improvement of small object detectability by SPECT, the most fruitful technological pursuit would probably involve development of focused collimators.

Routine castration in 568 draught colts: incidence of evisceration and omental herniation.

REASONS FOR PERFORMING STUDY: Castration is one of the most common routine surgical procedures performed in the horse, from which a number of potential complications can arise. We undertook a prospective evaluation of short-term complications associated with castration of draught colts over a 3-year period (1998-2000). OBJECTIVES: To compare castration complications in a large number of draught foals with previously published literature. METHODS: Five hundred and sixty-eight draught colts, age 4 or 5 months, were castrated in field conditions. Foals were observed for complications for 24 h post operatively. RESULTS: There was no significant difference in complication rates between open and closed surgical techniques. Inguinal/scrotal hernia rate was 4.6% (26/568) prior to surgery, and evisceration of the small intestine occurred in 4.8% (27/568). Foals observed to eviscerate underwent immediate surgical correction with an overall survival rate of 72.2% (13/18). Omental herniation was seen in 2.8% (16/568) of colts. CONCLUSIONS: This study showed no difference between the closed and open techniques of castration and the rate of omental herniation or evisceration. The evisceration rate in combination with the omental and presurgical herniation rates approached 12.2%, which is high enough to warrant further examination. POTENTIAL RELEVANCE: Future investigation should help to assess predisposing factors for evisceration. Regardless of the technique employed, herniation appears to pose a significant risk to draught foals undergoing castration.

An evaluation of the clinical pathologic findings in experimentally induced urinary bladder rupture in pre-ruminant calves.

The purpose of this project was to study the biochemical abnormalities that develop over time in preruminant calves with experimentally induced uroperitoneum. Uroperitoneum was produced by incising the bladder via a standing left flank laparotomy. Serum and peritoneal concentrations sodium, chloride, potassium, phosphate and creatinine were determined at 0, 2, 4, 8, 24, and 40 h. Serum creatinine concentration was increased by 8 h post-bladder rupture. Peritoneal concentrations of potassium and phosphate were significantly elevated 2 h after bladder rupture and peritoneal creatinine was significantly elevated by 4 h. Serum to peritoneal fluid ratios for potassium, phosphate and creatinine exceeded 2:1 within 2 h of bladder rupture. Pre-ruminant calves with experimentally induced uroperitoneum did not become hyperkalemic during the 40 h experiment.

Effects of potentiated chlorhexidine on bacteria and tarsocrural joints in ponies.

OBJECTIVES: To evaluate the bactericidal properties of chlorhexidine diacetate (CHD) after potentiation with EDTA and Tris buffer (EDTA-Tris), and to find a potentiated CHD concentration that would achieve 90 to 100% killing for all bacteria tested. ANIMALS: 6 adult ponies. PROCEDURES: Serial dilutions of CHD, CHD in EDTA-Tris and EDTA-Tris alone were evaluated for bactericidal activity against Staphylococcus aureus, Escherichia coli, and Streptococcus zooepidemicus. The tarsocrural joints of 6 ponies were lavaged with either 1 L phosphate-buffered saline solution (control) or 1 L of 0.0005% CHD in EDTA-Tris. Synovial fluid was collected before lavage and on days 1,4, and 8. Synovia, cartilage, and bone with cartilage were collected on day 8 when the ponies were euthanatized. RESULTS: In vitro results indicated that 0.0005% CHD in EDTA-Tris was 90% lethal to all bacteria tested. Results of synovial fluid analysis, glycosaminoglycan analysis, and histologic examination of the synovial membrane and articular cartilage indicated that joint lavage with 0.0005% CHD in EDTA-Tris was not detrimental to the synovium or the articular cartilage of pony tarsocrural joints. Changes observed were a result of the actual lavage process, the phosphate-buffered saline solution, and hemarthrosis. CONCLUSIONS: A concentration of 0.0005% CHD in EDTA-Tris was 90% lethal to all bacteria tested. Pony tarsocrural joint lavage with 0.0005% CHD in EDTA-Tris was not detrimental to the synovium or the articular cartilage. The efficacy of 0.0005% CHD potentiated with EDTA-Tris as a potential joint lavage fluid for treatment of infectious arthritis needs to be evaluated in clinical patients.

Synovial hernia as a possible complication of arthroscopic surgery in a horse.

A 3-year-old Standardbred gelding was referred for evaluation of a fluctuant swelling that developed over the dorsum of the carpus subsequent to arthroscopic surgery on that carpus. A synovial hernia was diagnosed and surgically repaired. Although complications secondary to arthroscopy are rare, synovial herniation can develop after arthroscopic surgery. The condition must be differentiated from the more common true bursitis or false bursitis that is commonly referred to as a hygroma.

Treatment of canker in horses.

Seven horses with canker had radical surgical debridement and various irritant substances applied to the wounds. Four of the horses were clinically normal in (mean) 3.6 months, 1 mare was lame, and 2 horses were euthanatized because of complications of their treatments. Seven horses that had minor surgical debridement and antimicrobial agents used systemically and topically were clinically normal in (mean) 1.4 months. Seemingly, canker in horses should be managed using minor surgical debridement and appropriate antimicrobial therapy.