Defining myocardial fibrosis in haemodialysis patients with non-contrast cardiac magnetic resonance.

BACKGROUND: Extent of myocardial fibrosis (MF) determined using late gadolinium enhanced (LGE) predicts outcomes, but gadolinium is contraindicated in advanced renal disease. We assessed the ability of native T1-mapping to identify and quantify MF in aortic stenosis patients (AS) as a model for use in haemodialysis patients. METHODS: We compared the ability to identify areas of replacement-MF using native T1-mapping to LGE in 25 AS patients at 3 T. We assessed agreement between extent of MF defined by LGE full-width-half-maximum (FWHM) and the LGE 3-standard-deviations (3SD) in AS patients and nine T1 thresholding-techniques, with thresholds set 2-to-9 standard-deviations above normal-range (1083 ± 33 ms). A further technique was tested that set an individual T1-threshold for each patient (T11SD). The technique that agreed most strongly with FWHM or 3SD in AS patients was used to compare extent of MF between AS (n = 25) and haemodialysis patients (n = 25). RESULTS: Twenty-six areas of enhancement were identified on LGE images, with 25 corresponding areas of discretely increased native T1 signal identified on T1 maps. Global T1 was higher in haemodialysis than AS patients (1279 ms ± 5.8 vs 1143 ms ± 12.49, P < 0.01). No signal-threshold technique derived from standard-deviations above normal-range associated with FWHM or 3SD. T11SD correlated with FWHM in AS patients (r = 0.55) with moderate agreement (ICC = 0.64), (but not with 3SD). Extent of MF defined by T11SD was higher in haemodialysis vs AS patients (21.92% ± 1 vs 18.24% ± 1.4, P = 0.038), as was T1 in regions-of-interest defined as scar (1390 ± 8.7 vs 1276 ms ± 20.5, P < 0.01). There was no difference in the relative difference between remote myocardium and regions defined as scar, between groups (111.4 ms ± 7.6 vs 133.2 ms ± 17.5, P = 0.26). CONCLUSIONS: Areas of MF are identifiable on native T1 maps, but absolute thresholds to define extent of MF could not be determined. Histological studies are needed to assess the ability of native-T1 signal-thresholding techniques to define extent of MF in haemodialysis patients. Data is taken from the PRIMID-AS (NCT01658345) and CYCLE-HD studies (ISRCTN11299707).

An extremely luminous panchromatic outburst from the nucleus of a distant galaxy.

Variable x-ray and γ-ray emission is characteristic of the most extreme physical processes in the universe. We present multiwavelength observations of a unique γ-ray-selected transient detected by the Swift satellite, accompanied by bright emission across the electromagnetic spectrum, and whose properties are unlike any previously observed source. We pinpoint the event to the center of a small, star-forming galaxy at redshift z = 0.3534. Its high-energy emission has lasted much longer than any γ-ray burst, whereas its peak luminosity was ∼100 times higher than bright active galactic nuclei. The association of the outburst with the center of its host galaxy suggests that this phenomenon has its origin in a rare mechanism involving the massive black hole in the nucleus of that galaxy.

Correlation of intra-operative duplex findings during carotid endarterectomy with neurological events and recurrent stenosis at one year.

OBJECTIVES: Carotid endarterectomy has been used to treat both asymptomatic and symptomatic disease and this has meant that recurrent stenosis and its effect on late stroke risk have become increasingly important. In this study we compared anatomical defects and residual stenosis identified intra-operatively with recurrent stenosis and new symptoms developing in the first year after surgery. DESIGN, MATERIALS & METHODS: Two hundred and forty-four consecutive patients undergoing carotid endarterectomy were studied prospectively. Residual anatomical defects were noted; residual stenosis was defined by intra-operative duplex ultrasound as >50%. New stenoses and clinical events during the one-year surveillance period were documented. RESULTS: There was an increased incidence of recurrent stenosis at one year in vessels with residual stenoses (p<0.001) and in vessels containing a residual anatomical defect (p=0.037). There was no significant difference in recurrent stenosis rate with respect to closure (primary or patch) or seniority of surgeon but recurrent stenosis was increased in females (p=0.026). The majority (70%) of restenotic lesions were localised to the origin of the internal carotid artery. The late stroke rate was 0.9% and was not related to recurrent stenosis or symptoms. CONCLUSIONS: Residual stenosis and intra-luminal defects at completion increase the recurrent stenosis rate at one year. The aetiology of recurrent stenosis is multi-factorial and further studies are required to determine whether it is justified to modify the criteria for re-exploration with a view to reducing recurrent stenosis.

Activation of ATP-ubiquitin-dependent proteolysis in skeletal muscle in vivo and murine myoblasts in vitro by a proteolysis-inducing factor (PIF).

Loss of skeletal muscle is a major factor in the poor survival of patients with cancer cachexia. This study examines the mechanism of catabolism of skeletal muscle by a tumour product, proteolysis-inducing factor (PIF). Intravenous administration of PIF to normal mice produced a rapid decrease in body weight (1.55 +/- 0.12 g in 24 h) that was accompanied by increased mRNA levels for ubiquitin, the Mr 14 000 ubiquitin carrier-protein, E2, and the C9 proteasome subunit in gastrocnemius muscle. There was also increased protein levels of the 20S proteasome core and 19S regulatory subunit, detectable by immunoblotting, suggesting activation of the ATP-ubiquitin-dependent proteolytic pathway. An increased protein catabolism was also seen in C(2)C(12)myoblasts within 24 h of PIF addition with a bell-shaped dose-response curve and a maximal effect at 2-4 nM. The enhanced protein degradation was attenuated by anti-PIF antibody and by the proteasome inhibitors MG115 and lactacystin. Glycerol gradient analysis of proteasomes from PIF-treated cells showed an elevation in chymotrypsin-like activity, while Western analysis showed a dose-related increase in expression of MSSI, an ATPase that is a regulatory subunit of the proteasome, with a dose-response curve similar to that for protein degradation. These results confirm that PIF acts directly to stimulate the proteasome pathway in muscle cells and may play a pivotal role in protein catabolism in cancer cachexia.

Value of intraoperative duplex imaging during supervised carotid endarterectomy.

BACKGROUND: For overall benefit, carotid endarterectomy requires low perioperative morbidity and mortality rates. Carotid thrombosis is usually secondary to technical error, which may be related to the experience of the operator. In this retrospective study the clinical and technical outcome of carotid endarterectomies performed by one consultant and five trainees were compared. METHODS: Some 149 patients underwent carotid endarterectomy; 89 were operated on by the consultant and 60 by trainees. Intraoperative duplex imaging of the carotid repair was performed before wound closure, and re-exploration was carried out when there was a residual severe stenosis associated with an intimal flap. RESULTS: There was no significant difference in clinical outcome between operations done by consultant or trainees. There was a significant increase in the number of stenoses, kinks and flaps in carotid endarterectomies performed by trainees compared with those of the consultant both before (chi2 = 12.0, 1 d.f., P < 0.001) and after (chi2 = 10.1, 1 d.f., P < 0.001) correction. CONCLUSION: Intraoperative duplex imaging may facilitate training by providing an objective assessment of the quality of the operation.

Distributive spirals: negotiation impasses and the moderating role of disputant self-efficacy.

Negotiations do not always end in agreements. Yet, we know little about impasses and how they affect negotiators. In three studies, we compare how negotiators experience impasses and agreements, paying particular attention to the moderating role of disputant self-efficacy. Specifically, we propose and find that negotiators who impasse find themselves caught in a distributive spiral-they interpret their performance as unsuccessful, experience negative emotions, and develop negative perceptions of their counterpart and the process. In terms of their future behavioral intentions, they are less willing to work together in the future, plan to share less information, plan to behave less cooperatively, and they lose faith in negotiation as an effective means of managing conflicts. As predicted, negotiators with relatively high levels of self-efficacy were insulated from some of these negative outcomes.

Azathioprine-associated acute myeloid leukaemia with trilineage dysplasia and complex karyotype: a case report and review of the literature.

A 66-year-old female with dermatomyositis (DM) who had received immunosuppressive therapy with azathioprine developed acute myeloid leukaemia (AML). Cytogenetic analysis revealed a complex karyotype including monosomy 7, and trilineage dysplastic features strongly suggestive of a treatment-related aetiology. The literature on azathioprine-associated AML is reviewed.

Carotid plaque characterization by duplex scanning: observer error may undermine current clinical trials.

BACKGROUND AND PURPOSE: Clinical studies currently in progress are using subjective methods to characterize plaque morphology from ultrasound images. However, there are few studies on the intraobserver and interobserver variability of these classifications. This study was designed to assess these variables. METHODS: Grading of plaque morphology from ultrasound images, stored both digitally and to hard copy, was performed by 2 classification schemes. Interobserver agreement was determined by 4 observers. Within-observer agreement was performed at intervals for up to 6 months. Accuracy of the 2 methods was determined by comparison with histology. RESULTS: Within- and between-observer agreement was moderate to good for full-color digital image analyses, with pooled kappa values of kappap=0.49+/-0.10 and kappap=0.62+/-0.07 for the 2-category method and kappap=0.53+/-0.06 and kappap=0.52+/-0.05 for the 4-category method, respectively. Hard copy data analyses gave lower kappa values. The more experienced observers produced higher within-observer agreements and higher correlation with histology. CONCLUSIONS: Reproducible grading of ultrasound images is not consistently achievable among experienced observers, and within-observer agreement may vary with time. The current subjective ultrasound characterization of carotid plaque morphology used in clinical trials may be associated with unacceptable levels of reproducibility in some centers. Variability between observers may be reduced by using the simpler 2-category grading of plaque morphology to interrogate full-color digitally stored images. Observer agreement should be audited regularly.

Trephination and suturing of avascular meniscal tears: a clinical study of the trephination procedure.

On the basis of animal studies, an arthroscopic surgical system and procedure of trephination plus suturing were designed for clinical practice. The system consists of a trephine with a tooth-like tip, a guide, and an ordinary arthroscopic power handle. The guide introduces the trephine to the tear without abrading articular cartilage and controls the depth of the trephination. The power handle connected to a suction system provides an inside-out cut core of meniscal tissue. Thirty-six patients with meniscal tears underwent arthroscopic trephination plus suturing (group TS) and 28 patients had suturing alone (group S). The follow-up was 25 to 78 months. Two symptomatic retears have occurred in group TS and 7 symptomatic retears in group S. The symptomatic retear rate of group TS was significantly smaller than group S (P < .01). It is indicated that the patients treated with trephination have fewer symptoms and lower clinical failure rate. Arthroscopic trephination is a safe and easy procedure.

Surgical management of congenital saccular cysts of the larynx.

Congenital saccular cysts of the larynx are unusual lesions that commonly present with respiratory obstruction in infants and children. The saccular cyst may result from an atresia of the laryngeal saccule orifice or may represent the retention of mucus in the collecting ducts of submucosal glands located around the ventricle. Traditionally, the treatment of the lesions has been endoscopic unroofing or marsupialization. Frequently, this modality requires multiple procedures as well as concomitant tracheotomy. There also have been reports of acquired subglottic stenosis. We have found that removal of the recurrent saccular cyst can be achieved relatively safely and effectively via a lateral cervical approach to the thyrohyoid membrane. We review our experience with four patients with congenital saccular cysts and detail the evaluation and surgical management of these lesions.

Event-related potentials as indices of display-monitoring performance.

We evaluated event-related potentials (ERP) as indices of performance in three visual display-monitoring tasks: (a) signal detection, (b) running memory and (c) computation. Using factor analysis, we developed a global measure of performance (PFI) for each task. Task-relevant and irrelevant-probe stimuli elicited ERPs, which included components P1, N1, P2, P300, slow waves, and fronto-central negativities. In tasks (a) and (b), P300 amplitude in the task-relevant ERPs increased when the task was engaged, and was greater for accurate-than for inaccurate-response trials. In tasks (a) and (c), the irrelevant-probe ERPs also differed among task and performance conditions. To relate ERP measures to PF1, we developed linear regression models distinguished by three factors: general versus individual-subject, stimulus relevance, and signal-to-noise ratio (SNR). Model accuracy and reliability were highest for individual-subject, relevant-stimulus and high-SNR models, where average R2 values for the three tasks were 0.44, 0.46, and 0.38, respectively. We discuss implications of the models for performance monitoring and implications of the ERP effects for human information processing.

Repairs by trephination and suturing of longitudinal injuries in the avascular area of the meniscus in goats.

Trephination may encourage healing of a tear in the avascular area of the meniscus, but healing may not be complete in unstable tears. We studied trephination with suture of longitudinal injuries in the avascular area of the medial meniscus in 20 goats; samples were studied at 3, 8, and 25 weeks. All 20 tears treated by trephination and suture were completely (4 samples) or partly (16 samples) healed. The average tensile strength of the healed repair was 40.4 kg/cm2 at 25 weeks. The level of DNA synthesis and tissue ingrowth decreased with time; DNA synthetic activity was also found in the chondrocytes of the menisci treated by suture alone. Only three of the menisci treated by suture alone were partly healed, and the remainder showed no gross evidence of healing. The addition of trephination to the sutured meniscus appears to promote healing of longitudinal injuries in the avascular area and is recommended rather than suturing or trephination alone. Meniscal suture alone may stabilize the tear and stimulate cell proliferation for healing, but it appears to be significantly restricted without an adequate blood supply.

Enzymatic production of hydrogen peroxide and acetaldehyde in a pressure reactor.

Alcohol oxidase, an enzyme which exhibits relatively weak substrate specificity among short chain alcohols, forms the corresponding aldehyde and hydrogen peroxide as coproduct. The ability of alcohol oxidase from Pichia pastoris yeast to convert ethanol to acetaldehyde and hydrogen peroxide was examined in an oxygen pressure reactor under conditions, such that oxygen availability was sufficient to permit rapid catalysis. Hydrogen peroxide levels of approximately 1.8/M (6% w/w) were attained in 2-3 h with 2.8 microM enzyme, corresponding to a productivity of approximately 30 g peroxide/g enzyme. Optimal conditions (within equipment limitations) were 900 psi oxygen, 2.6M ethanol, at 4 degrees C. Similar levels of products were reached in the reactor using enzyme immobilized covalently on controlled pore glass and noncovalently on an anion exchange support. Recycle of covalently immobilized enzyme was not possible as a result of enzyme inactivation after a single run. Limited recycle of noncovalently immobilized enzyme was accomplished with substantial decreases in levels of product attainable on each cycle.

A lateral extra-articular tenodesis for anterior cruciate ligament deficiency of the knee.

This article reviews patients with documented anterior cruciate ligament-deficient knees. Historical features are emphasized, and a rating system is provided. A lateral tenodesis is described, with timing of the repair and proper rehabilitation stressed.

Insulin stimulation of protein synthesis in cultured skeletal and cardiac muscle cells.

The effects of acute exposure to insulin on protein synthesis were examined in primary, differentiated cultures of embryonic chick heart and skeletal muscle cells. Synthetic rates were calculated using the specific activity of tRNA-bound leucine as precursor, a specific activity that was significantly less than that of extracellular leucine but greater than that of free, intracellular leucine at 0.2 mM external leucine. Insulin did not alter these relationships. Doses of insulin in the physiological range produced significant stimulation of protein synthesis in both cell types. Maximal responses, involving approximately 30% increases in both absolute and fractional rates, were observed at higher insulin concentrations. Significant stimulation by insulin was seen in cardiac cells after only 1 h of insulin treatment, and the effects of the hormone were observed both in the presence and absence of serum in the culture medium.

Protein synthesis in pulmonary alveolar macrophages. Source of amino acids for leucyl-tRNA.

Extracellular, intracellular and tRNA-bound leucine pools of the adherent pulmonary alveolar macrophage were examined to determine the relationships between them and the precursor for protein synthesis. When cells were cultured in media of various leucine concentrations, the patterns of isotope distribution in intracellular and extracellular leucine did not correlate with the patterns seen in protein-bound leucine. hence, the free leucine pools cannot be used reliably as precursors for calculating rates of protein synthesis. tRNA-bound leucine, however, behaved isotopically as if it were the precursor. Constant synthetic rates were calculated using the tRNA specific activity over a wide range of leucine concentrations. In addition, by measuring the tRNA-bound specific activities of three different amino acids, leucine, valine and phenylalanine, and their respective specific activities in protein, we were able to calculate independently three separate but identical synthetic rates. At physiological amino acid concentrations, the macrophage intracellular leucine pool and the tRNA-bound leucine pool received less than half of their amino acids from extracellular sources. At 5 mM external leucine, the intracellular specific activity was indistinguishable from that of the medium leucine, but the specific activity of the tRNA-bound leucine pool remained only about 50% that of the extracellular value. The most straightforward interpretation of why the tRNA-bound leucine did not flood with external label under conditions where the intracellular pool has reached equilibrium is to propose that some portion of the leucine for protein synthesis is derived directly from protein turnover before the degradation products have mixed with the common amino acid pool.

Treatment of acromioclavicular separations. A retrospective study.

A retrospective study of 134 patients with Types I, II, and III acromioclavicular separations was carried out. The average followup was 6.3 years, with the longest being 19 years, and the shortest being 1 year. The mechanism of injury was a direct blow in 92% of the patients. The average age of the patients was 30.1 years, with a range from 13 to 68 years. All patients were evaluated using a standard rating system for the shoulder and humerus, the total for perfect recovery being 100. Twenty-four patients with Type I separations were immobilized 19.5 days, with a disability period of 6 weeks, and rated 94 points. Twenty-five patients with Type II separations were immobilized 27 days for the conservative groups, had a disability period of 6 weeks, and rated 90 points. Eighty-five patients with Type III acromioclavicular separations were followed. Seven patients had conservative treatment, were immobilized an average of 22 days, with a disability period of 13 weeks, and rated 82. Of those patients who underwent surgical repair, excluding Dacron graft substitution, the immobilization period was 6 weeks, with a disability period of 12 weeks, and a rating of 80. Fifty-eight patients underwent repair with double velour Dacron prosthetic substitution for the coracoclavicular ligaments, combined with distal clavicular resection in all but two patients. The average immobilization period was 1 week, with the average disability period being 3 weeks. The average rating was 96, with 24 patients rating 100. The major cause for a rating less than 100 was light to moderate pain that persisted in a few cases, which was only occasional and associated with a particular activity. One infection occurred requiring graft removal 5 months after surgery. Calcification in the area of the coracoclavicular ligaments did not affect the final rating and recurrence of deformity was not noted.