Clinical features, microbiology and surgical outcomes of infective endocarditis: a 13-year study from a UK tertiary cardiothoracic referral centre.

BACKGROUND: Infective endocarditis (IE) causes substantial morbidity and mortality. Patient and pathogen profiles, as well as microbiological and operative strategies, continue to evolve. The impact of these changes requires evaluation to inform optimum management and identify individuals at high risk of early mortality. AIM: Identification of clinical and microbiological features, and surgical outcomes, among patients presenting to a UK tertiary cardiothoracic centre for surgical management of IE between 1998 and 2010. DESIGN: Retrospective observational cohort study. METHODS: Clinical, biochemical, microbiological and echocardiographic data were identified from clinical records. Principal outcomes were all-cause 28-day mortality and duration of post-operative admission. RESULTS: Patients (n = 336) were predominantly male (75.0%); median age 52 years (IQR = 41-67). Most cases involved the aortic (56.0%) or mitral (53.9%) valves. Microbiological diagnoses, obtained in 288 (85.7%) patients, included streptococci (45.2%); staphylococci (34.5%); Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella (HACEK) organisms (3.0%); and fungi (1.8%); 11.3% had polymicrobial infection. Valve replacement in 308 (91.7%) patients included mechanical prostheses (69.8%), xenografts (24.0%) and homografts (6.2%). Early mortality was 12.2%, but fell progressively during the study (P = 0.02), as did median duration of post-operative admission (33.5 to 10.5 days; P = 0.0003). Multivariable analysis showed previous cardiothoracic surgery (OR = 3.85, P = 0.03), neutrophil count (OR = 2.27, P = 0.05), albumin (OR = 0.94, P = 0.04) and urea (OR = 2.63, P < 0.001) predicted early mortality. CONCLUSIONS: This study demonstrates reduced post-operative early mortality and duration of hospital admission for IE patients over the past 13 years. Biomarkers (previous cardiothoracic surgery, neutrophil count, albumin and urea), predictive of early post-operative mortality, require prospective evaluation to refine algorithms, further improve outcomes and reduce healthcare costs associated with IE.

A randomized clinical trial of Cogmed Working Memory Training in school-age children with ADHD: a replication in a diverse sample using a control condition.

BACKGROUND: Cogmed Working Memory Training (CWMT) has received considerable attention as a promising intervention for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children. At the same time, methodological weaknesses in previous clinical trials call into question reported efficacy of CWMT. In particular, lack of equivalence in key aspects of CWMT (i.e., contingent reinforcement, time-on-task with computer training, parent-child interactions, supportive coaching) between CWMT and placebo versions of CWMT used in previous trials may account for the beneficial outcomes favoring CWMT. METHODS: Eighty-five 7- to 11-year old school-age children with ADHD (66 male; 78%) were randomized to either standard CWMT (CWMT Active) or a well-controlled CWMT placebo condition (CWMT Placebo) and evaluated before and 3 weeks after treatment. Dependent measures included parent and teacher ratings of ADHD symptoms; objective measures of attention, activity level, and impulsivity; and psychometric indices of working memory and academic achievement (Clinical trial title: Combined cognitive remediation and behavioral intervention for the treatment of Attention-Deficit/Hyperactivity Disorder; http://clinicaltrials.gov/ct2/show/NCT01137318). RESULTS: CWMT Active participants demonstrated significantly greater improvements in verbal and nonverbal working memory storage, but evidenced no discernible gains in working memory storage plus processing/manipulation. In addition, no treatment group differences were observed for any other outcome measures. CONCLUSIONS: When a more rigorous comparison condition is utilized, CWMT demonstrates effects on certain aspects of working memory in children with ADHD; however, CWMT does not appear to foster treatment generalization to other domains of functioning. As such, CWMT should not be considered a viable treatment for children with ADHD.

Dyspnoeic dysphasia: a series of unfortunate events.

We describe a case of a 56 year old man with no previous medical history who presented with sudden onset dyspnoea, expressive dysphasia, and right arm sensory loss and paresis. A diagnosis of bilateral pulmonary embolism and transient cerebral ischaemic attack was confirmed by CT pulmonary angiogram and MRI. Paradoxical embolism through an occult patent foramen ovale (PFO) was subsequently proven by contrast echocardiography. This case highlights a number of short and long-term management conundrums, that to date are incompletely addressed by clinical trials. These include timing of anticoagulation in patients with both venous thromboembolism and cerebral infarction, and the risk:benefit ratio of surgical closure of patent foramen ovale.

Adverse events to antituberculosis therapy: influence of HIV and antiretroviral drugs.

This study investigated whether serious adverse events (SAEs) during antituberculosis therapy occur more frequently in HIV co-infected patients in a South African population. A retrospective analysis examined incidences of hepatotoxicity, peripheral neuropathy, severe arthralgia, persistent vomiting and severe rash in 400 patients treated for tuberculosis in a community clinic. A total of 141 patients were co-infected with HIV, among whom only 16.3% were receiving antiretrovirals. Details of SAEs were ascertainable in 331/400 patients, and occurred in 26.7% of HIV-infected and 13.3% of HIV-uninfected individuals (P = 0.003). The excess was attributable to increased peripheral neuropathy (8.3% and 1.9%, respectively, P = 0.009) and persistent vomiting (13.3% and 3.3%, P = 0.001). SAE occurrence was not related to antiretroviral use, although median CD4 counts were lower in those experiencing side-effects (130 and 259 cells/microL, P = 0.008). The treatment completion did not differ significantly between the two groups (76.6% and 84.2%, P = 0.08).

Ileal MALT lymphoma causing massive gastrointestinal haemorrhage revealed on computed tomography angiography.

Primary MALT lymphomas affecting the ileum are rare, and their presentation with massive haemorrhage exceptional. This report describes such a case. The patient presented with melaena and haemodynamic instability, but normal upper gastrointestinal endoscopy. Subsequent imaging with multi-detector row computed tomography angiography both localised the bleeding source to the ileum and identified the underlying tumour, resulting in considerably earlier introduction of appropriate management. The patient made an excellent recovery and remains in remission.

Innate immunity in inflammatory bowel disease: a disease hypothesis.

Crohn's disease arises from a defective interaction between the highly concentrated mass of bacteria in the gastrointestinal tract and the underlying tissues. It has generally been believed to result from an excessively exuberant inflammatory response or from 'autoimmunity'. Recent evidence has emerged that the problem is instead a failure of the way in which the body responds to the penetration of bacteria and other bowel contents through the intestinal mucosal barrier. Rather than Crohn's disease being caused by excessive inflammation, the primary mechanism is actually that of an immunodeficiency. Failure of inflammatory mediator production leads to insufficient recruitment of neutrophils, resulting in inadequate removal of bacteria and other debris. This impairment of acute inflammation can be compensated in some circumstances by signalling through NOD2. If not cleared, the foreign material in the bowel wall is taken up within macrophages, eliciting a granulomatous reaction and the local and systemic sequelae so characteristic of Crohn's disease.

Modified skin window technique for the extended characterisation of acute inflammation in humans.

OBJECTIVE: To modify the skin window technique for extended analysis of acute inflammatory responses in humans, and demonstrate its applicability for investigating disease. SUBJECTS: 15 healthy subjects and 5 Crohn's patients. TREATMENT: Skin windows, created by dermal abrasion, were overlaid for various durations with filter papers saturated in saline, 100 ng/ml muramyl dipeptide (MDP) or 10 microg/ml interleukin-8 (IL-8). METHODS: Exuded leukocytes were analyzed by microscopy, immunoblot, DNA-bound transcription factor arrays and RT-PCR. Inflammatory mediators were quantified by ELISA. RESULTS: Infiltrating leukocytes were predominantly neutrophils. Numerous secreted mediators were detectable. MDP and IL-8 enhanced responses. Many signalling proteins were phosphorylated with differential patterns in Crohn's patients, notably PKC alpha/beta hyperphosphorylation (11.3 +/- 3.1 vs 1.2 +/- 0.9 units, P < 0.02). Activities of 44 transcription factors were detectable, and sufficient RNA isolated for expression analysis of over 400 genes. CONCLUSIONS: The modifications enable broad characterisation of inflammatory responses and administration of exogenous immunomodulators.

Impaired neutrophil chemotaxis in Crohn's disease relates to reduced production of chemokines and can be augmented by granulocyte-colony stimulating factor.

BACKGROUND: Defective neutrophil recruitment has been described as a primary pathogenic abnormality in Crohn's disease. Cantharidin-induced blisters provide a novel investigative tool to assess cellular influx and inflammatory mediator production during acute inflammation and allows the effects of therapy on these parameters to be measured. AIMS: To determine whether reduced neutrophil tissue penetration in Crohn's disease relates to impaired production of inflammatory mediators, and whether it can be reversed by granulocyte-colony stimulating factor (G-CSF). METHODS: Neutrophil and monocyte/macrophage populations and inflammatory mediators were measured in cantharidin blisters at 24 h. Neutrophil chemotaxis was assessed in vitro using blister fluid as the chemoattractant. The effect of s.c. G-CSF on blister phenotype was determined. RESULTS: Significantly fewer neutrophils migrated into blisters in Crohn's patients. The production of neutrophil chemokines, but not other inflammatory mediators, was reduced. This significantly correlated with reduced chemotaxis in vitro. Differences were unrelated to caspase-recruitment domain 15 genotype. G-CSF significantly increased blister neutrophil concentrations in control subjects and Crohn's patients. CONCLUSIONS: Reduced neutrophil migration during acute inflammation in Crohn's disease is associated with impaired production of appropriate chemoattractants. G-CSF therapy increases neutrophil tissue migration, which may partially account for its observed therapeutic effect.

Can unresolved infection precipitate autoimmune disease?

Autoimmune diseases are frequently postulated to arise as post-infectious phenomena. Here we survey the evidence supporting these theories, with particular emphasis on Crohn's disease and ankylosing spondylitis. Direct proof that infection establishes persistent autoimmunity remains lacking, although it may provoke a prolonged inflammatory response when occurring on a susceptible immunological background. The argument of infective causality is by no means trivial, since it carries important consequences for the safety of vaccine development.

Effects of supplemental fat on growth performance and quality of beef from steers fed barley-potato product finishing diets: I. Feedlot performance, carcass traits, appearance, water binding, retail storage, and palatability attributes.

To measure the effects of dietary fat on feedlot performance, carcass characteristics, and beef appearance, moisture binding, shelf life, and palatability, 168 crossbred beef steers (317 +/- 1.0 kg) were allotted randomly, within weight blocks, to a randomized complete block design with a 3 x2 + 1 factorial arrangement of dietary treatments. Main effects were level of yellow restaurant grease (RG; 0, 3, or 6%) and level of alfalfa hay (AH; 3.5 or 7%), with the added treatment of 6% tallow and 7% AH in barley-based diets containing 15% potato by-product and 7% supplement fed for 165 d (all dietary levels on a DM basis). Dietary treatment did not (P >0.10) affect DMI, LM area, beef brightness, or beef texture. Level of RG linearly increased (P <0.05) ADG from 1.48 to 1.60 kg/d, diet NE(m) from 2.4 to 2.6 Mcal/kg, diet NE(g) from 1.7 to 1.9 Mcal/kg, and internal fat from 2.1 to 2.4%. Level of RG linearly increased (P <0.05) G:F from 0.184 to 0.202, but decreased (P <0.05) beef firmness score from 3.0 to 2.8 and fat luster score from 3.1 to 2.8. Level of AH did not (P >0.10) affect any of the measurements; however, AH interacted with level of RG on fat thickness and yield grade (linear; P <0.05), as well as marbling score and percentage of carcasses grading USDA Choice (quadratic; P <0.05). Fat thickness and yield grade increased with increasing RG level in 3.5%, but not in 7%, AH diets. In steers fed 3.5% RG, marbling scores and percentage of carcasses grading Choice were greatest when fed with 3.5% AH, and least when fed 7% AH. Steers fed tallow had lower marbling scores (P = 0.01) and percentage of carcasses grading Choice (P = 0.066) than those fed RG. Retail storage attributes, including visual and instrumental color, decreased during storage (P <0.01), but were not (P >0.10) affected by diet. Trained sensory panel scores for initial tenderness increased quadratically (P = 0.07) as dietary RG increased, but diet did not (P >0.10) affect drip loss, cooking loss, or trained sensory panel scores for sustained tenderness, initial and sustained juiciness, and beef flavor. Therefore, RG increased diet energy, improved performance, and increased carcass fatness; however, dietary fat and AH did not affect most measurements of water retention, color stability, or palatability of beef.

Effects of supplemental fat on growth performance and quality of beef from steers fed barley-potato product finishing diets: II. Fatty acid composition of muscle and subcutaneous fat.

One hundred sixty-eight crossbred steers (317.1 +/- 1.0 kg) were used to evaluate the effects of supplemental fat in finishing diets on the fatty acid composition, including the 9,11 isomer of conjugated linoleic acid, of beef. Steers were allotted within three weight blocks to a randomized complete block design with a 3 x 2 + 1 factorial arrangement of dietary treatments. Main effects were level of yellow restaurant grease (RG; 0, 3, and 6%), and level of alfalfa hay (AH; 3.5 and 7%) with an added treatment containing 6% tallow (T) and 7% AH in barley-based diets containing 15% potato by-product and 7% supplement (all dietary levels are on a DM basis) fed for an average of 165 d. Fatty acids of the LM and s.c. fat from four randomly selected steers per pen were quantified using GC after methylation with sodium methoxide. Dietary treatment did not (P > 0.10) affect total fatty acid (FA) content of the LM (143 +/- 5.2 mg/g) or fat (958 +/- 7.9 mg/g). Myristic acid increased linearly (P < 0.01) with increasing RG from 3.1 to 3.7 +/- 0.1 g/100 g of FA in muscle. Stearic acid increased linearly (P < 0.05) as RG increased in the diet, from 11.4 to 12.9 +/- 0.4 g/100 g of FA in LM and from 9.9 to 12.2 +/- 0.3 g/100 g of FA in fat. Compared with T, steers fed 6% RG had more (P < 0.05) oleic acid in LM (42.7 vs. 40.3 +/- 0.5 g/100g FA) and in fat (43.0 vs. 40.9 +/- 0.5 g/100g FA). The cis-9, trans-11 conjugated linoleic acid (CLA) increased quadratically (P < 0.01) with increasing dietary RG in LM from 0.45 to 0.64 to 0.62 +/- 0.03 g/100 g of FA and increased in fat from 0.61 to 0.84 to 0.83 +/- 0.04 g/100 g of FA. Moreover, cis-9, trans-11 CLA was higher (P < 0.05) in fat from steers fed RG compared with T (0.81 vs. 0.69 +/- 0.04 g/100 g of FA), and tended to be higher (P = 0.07) in muscle (0.62 vs. 0.54 +/- 0.03 g/100 g of FA. Feeding yellow restaurant grease increased content of cis-9, trans-11 CLA in beef without an increase total FA content.

Effects of biological type and dietary fat treatment on factors associated with tenderness: I. Measurements on beef longissimus muscle.

The objective was to evaluate chemical, mechanical, and sensory attributes associated with tenderness in divergent cattle breeds--Wagyu (W; n = 12), Limousin (L; n = 12) and F1-cross (WxL; n = 12)--fed two dietary treatments (0 or 6% sunflower oil (DM basis)). A randomized complete block repeated measures design in a 3 x 2 factorial arrangement of treatments was used, and effects of breed, diet, block, and associated interactions were tested. Cattle were fed barley-based diets for an average of 259 d. Twenty-four hours postmortem (PM), steaks from the longissimus muscle (LM) were sliced, vacuum-packaged, aged (1, 3, 7, 14, 28, and 56 d PM) at 2 degrees C, and frozen (-40 degrees C) until analyzed. Wagyu steaks had lower (P < 0.05) Warner-Bratzler shear force (WBSF) values than L steaks across all aging times. At 1 d PM, W steaks required slightly more (P > 0.05) force to shear than WxL or L (0.30 and 0.11 kg, respectively); however, by d 14 PM, W steaks required 0.77 kg less (P < 0.05) force to shear than L. Wagyu steaks received higher (P < 0.05) sensory panel sustained tenderness scores at d 14 PM than L. The pH decline was slower (P < 0.05), and temperature decline more (P < 0.05) rapid, in W carcasses than L or WxL carcasses. Breed and diet did not affect (P > 0.10) free calcium levels (FCL) over time (0, 1, 3, 7, and 14 d PM), 0-h calpastatin activity (CA), d-1 percent collagen (OH-PRO), or d-1 collagen cross-linking (HP). Western blot analysis for the presence of the troponin-T (TNT) 30-kDa fragment, conducted only on samples from steers fed the 0% sunflower oil diet, demonstrated more proteolysis by d 3 PM in L than W or WxL. Overall, breed differences in mechanical and sensory measures of tenderness were not explained by FCL, CA, OH-Pro, and HP. Even though the initial appearance of the TNT 30-kDa fragment was greater in L, linear slopes for appearance of TNT degradation product across aging time were greater for W and WxL (P < 0.01 and P = 0.056, respectively) than for L, suggesting that tenderness differences due to breed may have been facilitated by more-rapid proteolytic degradation over time.

Effects of biological type and dietary fat treatment on factors associated with tenderness: II. Measurements on beef semitendinosus muscle.

The objective of this study was to evaluate attributes in semitendinosus muscle (ST) associated with tenderness in divergent breeds--Wagyu (W; n = 12), Limousin (L; n = 12), and Wagyu x Limousin cross cattle (WxL; n = 12)--fed two dietary treatments (0 or 6% sunflower oil, DM basis). A randomized complete block repeated measures design with a 3 x 2 factorial arrangement of treatments was used to measure effects of breed, diet, block, and associated interactions. Cattle were fed barley-based diets for an average of 259 d. Temperature and pH were measured at 0, 1, 3, 6, 12, and 24 h postmortem (PM). Steaks from the ST were removed 24 h postmortem, vacuum-packaged, aged (1, 3, 7, 14, 28, and 56 d postmortem) at 2 degrees C, and frozen (-40 degrees C) until analyzed. Dietary treatment did not (P > 0.10) affect Warner-Bratzler shear force (WBSF), collagen amount (OH-PRO) or cross-linking (HP), temperature, or pH. Steaks from WxL aged 14 d postmortem had lower (P < 0.05) WBSF values than L (W were intermediate). Cooking time was longer (P < 0.01) in W and WxL than in L; however, breed did not affect (P > 0.10) cooking loss. Cooking time was not influenced by diet, but steaks from cattle fed 6% sunflower oil had lower (P < 0.05) cooking losses. Temperature decreased more (P < 0.05) rapidly, and pH more slowly (P < 0.05), in W and WxL than L in the first 24 h postmortem. Limousin steaks were lighter (higher L*) and more yellow (higher b*) in color than steaks from W and WxL (P < 0.05). The control diet (no oil added) resulted in steaks that were lighter (P < 0.05) than the treatment diet (6% added sunflower oil). Neither breed nor diet affected (P > 0.10) OH-PRO or HP concentration. The results of this study indicate that biological type differences may not be as great in the ST as in longissimus muscle; thus, to increase tenderness in ST, emphasis may need to be placed on processing and cooking techniques rather than genetic selection.

Comorbidity in adults with attention-deficit/hyperactivity disorder.

This paper describes the clinical manifestations of attention-deficit/hyperactivity disorder (ADHD) in adulthood, with particular emphasis placed on issues relating to comorbidity. Prospective and retrospective studies are reviewed to evaluate the degree to which adults with ADHD exhibit clinical features that mirror their childhood counterparts with analogous comorbid psychiatric (e.g., antisocial, mood, and anxiety) and/or cognitive (i.e., learning) disorders. We also address the question of whether comorbid disorders in adults represent independent diagnostic entities and whether the presence of psychiatric comorbidity varies as a function of ADHD subtype (i.e., inattentive, hyperactive-impulsive, combined, and residual). As is the case for ADHD in childhood, comorbidity is not uncommon among adults with ADHD. However, the reported prevalence of comorbid conditions among adults with ADHD varies considerably depending upon whether the research used a prospective or retrospective design.

Predictors of physical aggression in children with attention-deficit/hyperactivity disorder.

The present investigation examined factors that predict physical aggression in children with attention-deficit/hyperactivity disorder (ADHD). Stepwise, multiple regression-analyses were used to examine predictors of children's physical aggression as rated by parents at a 1-year follow-up point and by teachers at both 1- and 2-year follow-up points. Early parent and teacher ratings of verbal aggression (ie, cursing, teasing, and threatening) accounted for the greatest proportion of the variance in physical aggression ratings obtained at follow-up. None of the other predictor variables, including early ratings of physical aggression and ADHD behaviors, contributed significant additional variance beyond that accounted for by early verbal aggression ratings. Temporal and cross-informant analyses revealed that the relationship between verbal aggression and later physical aggression was situation-specific for teacher ratings but not parent ratings. Although physical aggression may emerge early in development, these data suggest that verbal aggression represents a stable, temperamental characteristic that may be of greater value than early physical aggression for predicting later physically aggressive acts.

Identification of AD/HD subtypes using laboratory-based measures: a cluster analysis.

The current investigation used laboratory-based measures of inattention, impulsivity, and activity level to identify subgroups of children with attention-deficit/hyperactivity disorder (AD/HD). Data derived from solid state actigraphs and a continuous performance test (CPT) were obtained from a clinically referred sample and submitted to a cluster analysis. These empirically derived groups were then evaluated for clinical relevance and subsequently validated by parent and teacher ratings and tests of intellectual functioning and academic achievement. Four distinct subgroups emerged: Hyperactive-inattentive (HYP-IN), impulsive-inattentive (IMP-IN), inattentive only, and hyperactive only. The HYP-IN group was impaired on measures of intellectual functioning and academic achievement relative to the other three groups. In contrast, the IMP-IN group was generally rated as more aggressive, although this difference was not statistically significant for all measures. The data suggest that the augmentation of clinical descriptors with laboratory-based data may be an effective strategy by which to categorize diagnostic subgroups of AD/HD.