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Objectives: The aims of this study were to quantify preoperative myocardial fibrosis using late gadolinium enhancement (LGE), extracellular volume fraction (ECV%), and indexed extracellular volume (iECV) on cardiac magnetic resonance; determine whether this varies following surgery; and examine the impact on postoperative outcomes., Background: Myocardial fibrosis complicates chronic severe primary mitral regurgitation and is associated with left ventricular dilatation and dysfunction. It is not known if this nonischemic fibrosis is reversible following surgery or if it affects ventricular remodeling and patient outcomes., Methods: A multicenter prospective study was conducted among 104 subjects with primary mitral regurgitation undergoing mitral valve repair. Cardiac magnetic resonance and cardiopulmonary exercise stress testing were performed preoperatively and ≥6 months after surgery. Symptoms were assessed using the Minnesota Living With Heart Failure Questionnaire., Results: Mitral valve repair was performed for Class 2a indications in 65 patients and Class 1 indications in 39 patients. Ninety-three patients were followed up at 8.8 months (IQR: 7.4 months-10.6 months). Following surgery, there were significant reductions in both ECV% (from 27.4% to 26.6%; P = 0.027) and iECV (from 17.9 to 15.4 mL/m 2 ; P < 0.001), but the incidence of LGE was unchanged. Neither preoperative ECV% nor LGE affected postoperative function, but iECV predicted left ventricular end-systolic volume index (β = 1.04; 95% CI: 0.49 to 1.58; P < 0.001) and left ventricular ejection fraction (β = -0.61; 95% CI: -1.05 to -0.18; P = 0.006). Patients with above-median iECV of ≥17.6 mL/m 2 had significantly larger postoperative values of left ventricular end-systolic volume index (30.5 ± 12.7 mL/m 2 vs 23.9 ± 8.0 mL/m 2 ; P = 0.003), an association that remained significant in subcohort analyses of patients in New York Heart Association functional class I., Conclusions: Mitral valve surgery results in reductions in ECV% and iECV, which are surrogates of diffuse myocardial fibrosis, and preoperative iECV predicts the degree of postoperative remodeling irrespective of symptoms. (The Role of Myocardial Fibrosis in Degenerative Mitral Regurgitation; NCT02355418)., Competing Interests: Funding Support and Author Disclosures This research was fully funded by the British Heart Foundation (PG/14/74/31056). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Mycobacterium chimaera ( M. chimaera) is a recently characterised bacterium that can cause life-threatening infections in small numbers of patients who undergo cardiopulmonary bypass during cardiac surgery. The likely mode of transmission is thought to occur through aerosolisation from contaminated water reservoirs. The airborne bacteria then contaminate the surgical field, leading to an infection months or even years later. The preferred practical solution to disrupt the transmission of these airborne bacteria to the patient is to remove the heater-cooler units (HCUs) from the operating room (OR). We describe a process of achieving this in order to provide information to guide other institutions who wish to do a similar thing., Methods: A multidisciplinary team was assembled to work on the project. The planning phase involved trialling different OR layouts and simulating the alterations in the HCU circuit function. The changes to the OR were made over a weekend to minimise disruption to the operating schedule., Results: The HCU was moved to the dirty utility room adjacent to the OR. Standard operating procedures (SOP) and risk assessments were made to enable this to be used for a dual purpose. One of the ORs was reconfigured to allow the cardiopulmonary bypass machine to be located close to the HCU in the dirty utility room. The total cost of the alterations was £6,158. Although we have provided a physical barrier to interrupt patient exposure to aerosolised M. chimaera from HCUs, we continue to perform cultures and decontamination as per the national recommendations. The SOP was designed to be auditable to ensure compliance with the protocols., Conclusions: We show a method by which the HCU can be removed from the OR in a relatively low-cost, straightforward and practical manner.

Background/objectives: In obesity, improved muscle insulin sensitivity following exercise training has been linked to the lowering of diacylglycerol (DAG) and ceramide concentrations. Little is known, however, about how improved insulin action with exercise training in obese individuals relates to lipid droplet (LD) adaptations in skeletal muscle. In this study we investigated the hypothesis that short-term sprint interval training (SIT) and moderate-intensity continuous training (MICT) in obese individuals would increase perilipin (PLIN) expression, increase the proportion of LDs in contact with mitochondria and reduce muscle concentrations of DAGs and ceramides., Methods: Sixteen sedentary obese males performed 4 weeks of either SIT (4-7 × 30 s sprints at 200% W max , 3 days week) or MICT (40-60 min cycling at ~65% VO 2peak , 5 days per week), and muscle biopsies were obtained pre- and post-training., Results: Training increased PLIN2 (SIT 90%, MICT 68%) and PLIN5 (SIT 47%, MICT 34%) expression in type I fibres only, and increased PLIN3 expression in both type I (SIT 63%, MICT 67%) and type II fibres (SIT 70%, MICT 160%) (all P<0.05). Training did not change LD content but increased the proportion of LD in contact with mitochondria (SIT 12%, MICT 21%, P<0.01). Ceramides were reduced following training (SIT -10%, MICT -7%, P<0.05), but DAG was unchanged. No training × group interactions were observed for any variables., Conclusions: These results confirm the hypothesis that SIT and MICT results in remodelling of LDs and lowers ceramide concentrations in skeletal muscle of sedentary obese males.

Key Points: Skeletal muscle capillary density and vasoreactivity are reduced in obesity, due to reduced nitric oxide bioavailability. Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), but its effect on the skeletal muscle microvasculature has not been studied in obese individuals. We observed that SIT and MICT led to equal increases in capillarisation and endothelial eNOS content, while reducing endothelial NOX2 content in microvessels of young obese men. We conclude that SIT is equally effective at improving skeletal muscle capillarisation and endothelial enzyme balance, while being a time efficient alternative to traditional MICT., Abstract: Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), leading to similar improvements in skeletal muscle capillary density and microvascular function in young healthy humans. In this study we made the first comparisons of the muscle microvascular response to SIT and MICT in an obese population. Sixteen young obese men (age 25 ± 1 years, BMI 34.8 ± 0.9 kg m(-2) ) were randomly assigned to 4 weeks of MICT (40-60 min cycling at ∼65% V̇O2 peak , 5 times per week) or constant load SIT (4-7 constant workload intervals of 200% Wmax 3 times per week). Muscle biopsies were taken before and after training from the m. vastus lateralis to measure muscle microvascular endothelial eNOS content, eNOS serine(1177) phosphorylation, NOX2 content and capillarisation using quantitative immunofluorescence microscopy. Maximal aerobic capacity (V̇O2 peak ), whole body insulin sensitivity and arterial stiffness were also assessed. SIT and MICT increased skeletal muscle microvascular eNOS content and eNOS ser(1177) phosphorylation in terminal arterioles and capillaries (P < 0.05), but the latter effect was eliminated when normalised to eNOS content (P = 0.217). SIT and MICT also reduced microvascular endothelial NOX2 content (P < 0.05) and both increased capillary density and capillary-fibre perimeter exchange index (P < 0.05). In parallel, SIT and MICT increased V̇O2 peak (P < 0.05) and whole body insulin sensitivity (P < 0.05), and reduced central artery stiffness (P < 0.05). As no significant differences were observed between SIT and MICT it is concluded that SIT is a time efficient alternative to MICT to improve aerobic capacity, insulin sensitivity and muscle capillarisation and endothelial eNOS/NAD(P)Hoxidase protein ratio in young obese men., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Objective: The effects of RT on muscle mass, strength, and insulin sensitivity are well established, but the underlying mechanisms are only partially understood. The main aim of this study was to investigate whether RT induces changes in endothelial enzymes of the muscle microvasculature, which would increase NO bioavailability and could contribute to improved insulin sensitivity., Methods: Eight previously sedentary males (age 20 ± 0.4 years, BMI 24.5 ± 0.9 kg/m(2) ) completed six weeks of RT 3x/week. Muscle biopsies were taken from the m. vastus lateralis and microvascular density; and endothelial-specific eNOS content, eNOS Ser(1177) phosphorylation, and NOX2 content were assessed pre- and post-RT using quantitative immunofluorescence microscopy. Whole-body insulin sensitivity (measured as Matsuda Index), microvascular Kf (functional measure of the total available endothelial surface area), and arterial stiffness (AIx, central, and pPWV) were also measured., Results: Measures of microvascular density, microvascular Kf , microvascular eNOS content, basal eNOS phosphorylation, and endothelial NOX2 content did not change from pre-RT to post-RT. RT increased insulin sensitivity (p < 0.05) and reduced resting blood pressure and AIx (p < 0.05), but did not change central or pPWV., Conclusions: RT did not change any measure of muscle microvascular structure or function., (© 2014 John Wiley & Sons Ltd.)

Recent in vitro and in vivo experimental observations suggest that improvements in insulin sensitivity following endurance training are mechanistically linked to increases in muscle oxidative capacity, intramuscular triglyceride (IMTG) utilization during endurance exercise and increases in the content of the lipid droplet-associated perilipin 2 (PLIN2) and perilipin 5 (PLIN5). This study investigated the hypothesis that similar adaptations may also underlie the resistance training (RT)-induced improvements in insulin sensitivity. Thirteen sedentary men (20 ± 1 years old; body mass index 24.8 ± 0.8 kg m(-2)) performed 6 weeks of whole-body RT (three times per week), and changes in peak O2 uptake (in millilitres per minute per kilogram) and insulin sensitivity were assessed. Muscle biopsies (n = 8) were obtained before and after 60 min steady-state cycling at ~65% peak O2 uptake. Immunofluorescence microscopy was used to assess changes in oxidative capacity (measured as cytochrome c oxidase protein content), IMTG and PLIN2 and PLIN5 protein content. Resistance training increased peak O2 uptake (by 8 ± 3%), COX protein content (by 46 ± 13 and 61 ± 13% in type I and II fibres, respectively) and the Matsuda insulin sensitivity index (by 47 ± 6%; all P < 0.05). In type I fibres, IMTG (by 52 ± 11%; P < 0.05) and PLIN2 content (by 107 ± 19%; P < 0.05) were increased and PLIN5 content tended to increase (by 54 ± 22%; P = 0.054) post-training. In type II fibres, PLIN2 content increased (by 57 ± 20%; P < 0.05) and IMTG (by 46 ± 17%; P = 0.1) and PLIN5 content (by 44 ± 24%; P = 0.054) tended to increase post-training. Breakdown of IMTG during moderate-intensity exercise was greater in both type I and type II fibres (by 43 ± 5 and 37 ± 5%, respectively; P < 0.05) post-RT. The results confirm the hypothesis that RT enhances muscle oxidative capacity and increases IMTG breakdown and the content of PLIN2 and PLIN5 in both type I and type II fibres during endurance-type exercise., (© 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.)

Intramuscular triglyceride (IMTG) utilization is enhanced by endurance training (ET) and is linked to improved insulin sensitivity. This study first investigated the hypothesis that ET-induced increases in net IMTG breakdown and insulin sensitivity are related to increased expression of perilipin 2 (PLIN2) and perilipin 5 (PLIN5). Second, we hypothesized that sprint interval training (SIT) also promotes increases in IMTG utilization and insulin sensitivity. Sixteen sedentary males performed 6 weeks of either SIT (4-6, 30 s Wingate tests per session, 3 days week(-1)) or ET (40-60 min moderate-intensity cycling, 5 days week(-1)). Training increased resting IMTG content (SIT 1.7-fold, ET 2.4-fold; P < 0.05), concomitant with parallel increases in PLIN2 (SIT 2.3-fold, ET 2.8-fold; P < 0.01) and PLIN5 expression (SIT 2.2-fold, ET 3.1-fold; P < 0.01). Pre-training, 60 min cycling at ∼65% pre-training decreased IMTG content in type I fibres (SIT 17 ± 10%, ET 15 ± 12%; P < 0.05). Following training, a significantly greater breakdown of IMTG in type I fibres occurred during exercise (SIT 27 ± 13%, ET 43 ± 6%; P < 0.05), with preferential breakdown of PLIN2- and particularly PLIN5-associated lipid droplets. Training increased the Matsuda insulin sensitivity index (SIT 56 ± 15%, ET 29 ± 12%; main effect P < 0.05). No training × group interactions were observed for any variables. In conclusion, SIT and ET both increase net IMTG breakdown during exercise and increase in PLIN2 and PLIN5 protein expression. The data are consistent with the hypothesis that increases in PLIN2 and PLIN5 are related to the mechanisms that promote increased IMTG utilization during exercise and improve insulin sensitivity following 6 weeks of SIT and ET.

Sprint interval training (SIT) has been proposed as a time efficient alternative to endurance training (ET) for increasing skeletal muscle oxidative capacity and improving certain cardiovascular functions. In this study we sought to make the first comparisons of the structural and endothelial enzymatic changes in skeletal muscle microvessels in response to ET and SIT. Sixteen young sedentary males (age 21 ± SEM 0.7 years, BMI 23.8 ± SEM 0.7 kg m(-2)) were randomly assigned to 6 weeks of ET (40-60 min cycling at ∼65% , 5 times per week) or SIT (4-6 Wingate tests, 3 times per week). Muscle biopsies were taken from the m. vastus lateralis before and following 60 min cycling at 65% to measure muscle microvascular endothelial eNOS content, eNOS serine(1177) phosphorylation, NOX2 content and capillarisation using quantitative immunofluorescence microscopy. Whole body insulin sensitivity, arterial stiffness and blood pressure were also assessed. ET and SIT increased skeletal muscle microvascular eNOS content (ET 14%; P < 0.05, SIT 36%; P < 0.05), with a significantly greater increase observed following SIT (P < 0.05). Sixty minutes of moderate intensity exercise increased eNOS ser(1177) phosphorylation in all instances (P < 0.05), but basal and post-exercise eNOS ser(1177) phosphorylation was lower following both training modes. All microscopy measures of skeletal muscle capillarisation (P < 0.05) were increased with SIT or ET, while neither endothelial nor sarcolemmal NOX2 was changed. Both training modes reduced aortic stiffness and increased whole body insulin sensitivity (P < 0.05). In conclusion, in sedentary males SIT and ET are effective in improving muscle microvascular density and eNOS protein content.

The lipid droplet (LD)-associated protein perilipin 2 (PLIN2) appears to colocalize with LDs in human skeletal muscle fibres, although the function of PLIN2 in the regulation of intramuscular triglyceride (IMTG) metabolism is currently unknown. Here we investigated the hypothesis that the presence of PLIN2 in skeletal muscle LDs is related to IMTG utilisation during exercise. We therefore measured exercise-induced changes in IMTG and PLIN2 distribution and changes in their colocalization. Muscle biopsies from the vastus lateralis were obtained from seven lean, untrained men (22 ± 2 years old, body mass index 24.2 ± 0.9 kg m(-2) and peak oxygen uptake 3.35 ± 0.13 l min(-1)) before and after 1 h of moderate-intensity cycling at ~65% peak oxygen uptake. Cryosections were stained for perilipin 2, IMTG and myosin heavy chain type I and viewed using wide-field and confocal fluorescence microscopy. Exercise induced a 50 ± 7% decrease in IMTG content in type I fibres only (P < 0.05), but no change in PLIN2 content. Colocalization analysis showed that the fraction of PLIN2 associated with IMTG was 0.67 ± 0.03 before exercise, which was reduced to 0.51 ± 0.01 postexercise (P < 0.05). Further analysis revealed that the number of PLIN2-associated LDs was reduced by 31 ± 10% after exercise (P < 0.05), whereas the number of PLIN2-null LDs was unchanged. No such changes were seen in type II fibres. In conclusion, this study shows that PLIN2 content in skeletal muscle is unchanged in response to a single bout of endurance exercise. Furthermore, the PLIN2 and IMTG association is reduced postexercise, apparently due to preferential utilization of PLIN2-associated LDs. These results confirm the hypothesis that the PLIN2 association with IMTG is related to the utilization of IMTG as a fuel during exercise.

We report a rare case of an intrathymic primary intrathoracic goiter. The patient with newly diagnosed breast carcinoma was also known to have a distinct large anterior mediastinal mass. This was removed via a median sternotomy, after a thorascopic biopsy had been performed in the past but a diagnosis had not been reached. A discussion relating to the extremely rare occurrence of intrathymic ectopic thyroid tissue and the surgical treatment of primary intrathoracic goiters is included., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Entering the clinical environment is potentially stressful for junior medical students., Aims: We evaluated first-year medical student feedback on a peer-mentored 'Hospital Orientation Day' designed to provide insight into future clinical training., Method: Using a mixed methodology approach data were collected from first-year medical students. Responses to a questionnaire were used to develop a topic guide for focus groups held the next academic year. The questionnaire was completed by 230 first-year students and 32 second years participated in the interviews. Thematic analysis was used to draw conclusions., Results: Analysis of questionnaire responses indicated that students gained insight into future learning. Focus groups then generated five themes: (1) entering the hospital without fear, (2) linking the present with the future, (3) understanding the culture of learning in the clinical years, (4) a 'Backstage Pass' to the clinical world and (5) peer mentors make or break the day., Conclusions: Using peer mentors during the Hospital Orientation Day allowed insight into future learning. We highlight the importance of student Mentors in the success of hospital orientation. To maximise the benefits for first years, we recommend a mentor selection procedure, mentor training opportunities and incentives to optimise mentor performance.

Background: Limb electrodes for the 12 lead ECG are routinely placed on the torso during exercise stress testing or when limbs are clinically inaccessible. It is unclear whether such electrode modification produces ECG changes in healthy male or female subjects that are clinically important according to the 2009 AHA, ACCF, HRS guidelines. We therefore measured whether ECG modification produced clinically important or false positive ECG changes e.g., appearance of Q waves in leads V(1-3), ST changes greater than 0.1 mV, T wave changes greater than 0.5 mV (frontal plane) or 1 mV (transverse plane), QRS axis shifts or alterations to QTc/P-R/QRS intervals., Methods: The 12 lead ECG was measured in 18 healthy and semi-recumbent subjects using the standard and Takuma modified limb placements., Results: In the frontal plane we demonstrate that the modification of limb electrode placement produces small Q, R and T wave amplitude and QRS axis changes that are statistically but not clinically significant. In the transverse plane it produces no statistically or clinically significant changes in the ECG or in ST segment morphology, P-R, QRS or QTc intervals., Conclusions: We provide better and more robust evidence that routine modification of limb electrode placement produces only minor changes to the ECG waveform in healthy subjects. These are not clinically significant according to the 2009 guidelines and thus have no effect on the clinical specificity of the 12 lead ECG., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Functionalized cyclohexanones are prepared from cyclic enol ethers via a Pd-catalyzed [1,3]-O-to-C rearrangement reaction. α-Arylketones are generated with excellent diastereocontrol when basic phosphine ligands are used. In contrast, a Lewis acid is required to promote the rearrangement of the alkyl-substituted enol ether systems.

High rates of depression have been observed among men who have sex with men (MSM) relative to the general adult male population; however, a dearth of research has explored depression among Black MSM. Black MSM (n = 197) recruited via modified respondent-driven sampling between January and July 2008 completed an interviewer-administered quantitative assessment and voluntary HIV counseling and testing. Bivariate and multivariable logistic regression procedures examined the associations of demographics, behavioral HIV risk factors, and psychosocial variables with depressive symptoms by severity, using the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Adjusting for demographic and behavioral variables, significant factors associated with (1) clinically significant depressive symptoms (33%; CES-D score > or = 16): being publicly insured by Medicaid, having serodiscordant anal sex with a casual male partner, and being diagnosed with an STD in the prior 12 months; (2) moderate depressive symptoms (19%; CES-D score 16-26): having serodiscordant unprotected anal sex with a casual male partner and being diagnosed with an STD in the prior 12 months; (3) severe depressive symptoms (14%; CES-D score 27+): being publicly insured by Medicaid and reporting difficulty accessing healthcare in the past 12 months. Moderately depressed Black MSM may be more likely to engage in behaviors that place them at increased risk for HIV and other STDs. HIV prevention interventions for Black MSM may benefit from incorporating screening and/or treatment for depression, allowing MSM who are depressed to respond more effectively to behavioral change approaches.

Objective: High concentrations of potassium and lactate in irradiated red cells transfused during cardiopulmonary bypass may have detrimental effects on infants and neonates undergoing cardiac surgery. The effects of receiving washed and unwashed irradiated red cells from the cardiopulmonary circuit on serum potassium and lactate concentrations were compared., Methods: The study population included neonates and infants undergoing heart surgery for complex congenital heart disease. A control group (n=11) received unwashed irradiated red cells and the study group (n=11) received irradiated red cells washed in a cell saver (Dideco Electa) using 900ml of 0.9% saline prior to pump priming. Potassium and lactate concentrations were compared before, during and after bypass., Results: Washing irradiated red cells reduced donor blood [potassium] from>20 to 0.8+/-0.1mmol/l, and [lactate] from 13.7+/-0.5 to 5.0+/-0.3mmol/l (p<0.001). The resulting prime had significantly lower [potassium] and [lactate] than the unwashed group (potassium 2.6+/-0.1 vs 8.1+/-0.4mmol/l, p<0.001; lactate 2.6+/-0.2 vs 4.6+/-0.3mmol/l, p<0.001). Peak [potassium] in the unwashed group occurred 3 minutes after going on bypass (4.9+/-0.3mmol/l) and during rewarming (4.9+/-0.4mmol/l). These were significantly higher than the washed group (3.1+/-0.1, p<0.001 and 3.0+/-0.1mmol/l, p<0.001). The [potassium] was greater than 6.0mmol/l for 4 out of these 11 unwashed patients compared with none of the washed group. Immediately post-bypass the washed group had significantly lower serum [potassium] (3.2+/-0.1 vs 4.2+/-0.2mmol/l, p=0.002). There was no significant difference in [lactate] between groups during and after cardiopulmonary bypass., Conclusions: The washing of irradiated red cells reduces potassium and lactate loads and prevents hyperkalaemia during cardiopulmonary bypass. The washing of irradiated red cells should be considered in neonates and infants undergoing cardiac surgery for complex congenital heart disease.

It has been suggested that the effects of angiotensin II type 1 receptor (AT1R) blockers are in part because of angiotensin II type 2 receptor (AT2R) signaling. Interactions between the AT2R and kinins modulate cardiovascular function. Because AT2R expression increases after vascular injury, we hypothesized that the effects on vascular remodeling of the AT1R blocker valsartan and the ACE inhibitor benazepril require AT2R signaling through the bradykinin 1 and 2 receptors (B1R and B2R). To test this hypothesis, Brown Norway rats were assigned to 8 treatments (n=16): valsartan, valsartan+PD123319 (AT2R inhibitor), valsartan+des-arg9-[Leu8]-bradykinin (B1R inhibitor), valsartan+HOE140 (B2R inhibitor), benazepril, benazepril+HOE140, amlodipine, and vehicle. After 1 week of treatment, carotid balloon injury was performed. Two weeks later, carotids were harvested for morphometry and analysis of receptor expression by immunohistochemistry and Western blotting. Valsartan and benazepril significantly reduced the intima:media ratio compared with vehicle. Blockade of AT2R, B1R, or B2R in the presence of valsartan prevented the reduction seen with valsartan alone. B2R blockade inhibited the effect of benazepril. Injury increased AT1R, AT2R, B1R, and B2R expression. Treatment with valsartan but not benazepril significantly increased intima AT2R expression 2-fold compared with vehicle, which was not reversed by inhibition of AT2R, B1R, and B2R. Functionally, valsartan increased intimal cGMP levels compared with vehicle, and this increase was inhibited by blocking the AT2R, B1R, and B2R. Results suggest that AT2R expression and increased cGMP represent a molecular mechanism that differentiates AT1R blockers, such as valsartan, from angiotensin-converting enzyme inhibitors like benazepril.

We report a novel off-pump technique for the surgical closure of post-infarct ventricular septal defects (VSDs). The case report describes the peri-operative management of a 76 year old lady who underwent the 'Hamburger procedure' for closure of her apical VSD. Refractory cardiogenic shock meant that traditional patch repairs requiring cardiopulmonary bypass would be poorly tolerated. We show that echocardiography guided off-pump posterior-anterior septal plication is a safe, effective method for closing post-infarct VSDs in unstable patients. More experience is required to ascertain whether this technique will become an accepted alternative to patch repairs.

The initial view of the renin-angiotensin system focused on the role of angiotensin II as a hormone involved in blood pressure control, based on its role in renal salt and water regulation, as well as central nervous system (thirst) and vascular smooth muscle tone. Subsequent data showed a role for angiotensin II in long-term effects on cardiovascular structure, including cardiac hypertrophy and vascular remodeling. Importantly, recent human studies with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have demonstrated exciting clinical benefits including decreases in incidence of stroke, diabetes, and end-stage renal disease that suggest important new mechanisms of action. In this review, we focus on new roles for the renin-angiotensin system in the endothelium based on the concepts of diverse signals and effects mediated by multiple angiotensin I- and angiotensin II-derived peptides, multiple angiotensin metabolizing enzymes, multiple receptors, and vascular bed-specific intracellular signals.

The incidence of acute rheumatic fever has seen a dramatic decline over the last 15 to 20 years in most developed countries and treatment of this disease has changed little since. The ease of travel and immigration and the cosmopolitan nature of many cities mean that occasionally the disease will come to the attention of clinicians not familiar with its presentation, resulting in delayed diagnosis and treatment. We present a case of recurrent acute rheumatic fever in a patient who was initially thought to be suffering from acute bacterial endocarditis on her previously diseased rheumatic aortic valve. This culminated in her undergoing urgent aortic valve replacement during a phase of the illness that should have been treated with high dose anti-inflammatory medication. Therefore, clinicians should be aware of this condition and include it in their differential diagnosis of the febrile patient with a previous history of rheumatic fever. We briefly discuss the diagnostic dilemma of patients suffering from this condition and in differentiating it from acute endocarditis.

Objective: To present the 5-year experience of the northwest of England's surgical repair of post myocardial infarction (MI) ventricular septal defects (VSD). Our primary aim was to evaluate the effect of concomitant coronary artery bypass grafting (CABG) on mid-term survival and also to identify prognostic indicators., Methods: A multi-centre regional observational study involving clinical data from 65 consecutive patients who underwent post MI VSD repair in the northwest of England between April 1997 and March 2002. Both prospective and retrospective collection of preoperative, operative and postoperative information was performed. Patient follow-up was performed by linking their records to the National Strategic Tracing Service database. Multivariate logistic regression and Cox proportional hazards analyses were used to identify independent risk factors for poor prognosis., Results: Of the 65 patients included in the study, 42 (64.6%) underwent concomitant CABG with a median of two grafts. The majority of patients who had their coronary arteries grafted had multivessel disease (92.9%). Overall 30-day mortality was 23.1%. Predictors of poor prognosis included preoperative inotropes (P<0.001) and total occlusion of infarct related artery (P=0.03). The crude hazard ratio (HR) of mid-term mortality for concomitant CABG patients was 0.82 [95% confidence interval (CI) 0.38-1.78; P=0.62]. After adjustment for differences in patient and disease characteristics, the adjusted HR of mid-term mortality for concomitant CABG patients was 0.17 (95% CI 0.04-0.74; P=0.019). The adjusted freedom from death in the concomitant CABG patients at 30 days, 1, 2, and 4 years was 96.2%, 91.6%, 88.8%, and 82.8%, respectively, compared with 79.1%, 58.8%, 49.1%, and 32.2% for the non-concomitant CABG patients., Conclusion: These data provide evidence that concomitant CABG is significantly beneficial to mid-term mortality rates. We recommend that patients who present with post MI VSD who have multivessel disease should be routinely revascularised.

We conducted a prospective study to determine the relationship between central (CVP) and peripheral (PVP) venous pressures in critically ill patients. CVP and PVP were measured on five different occasions in 20 critically ill patients in the intensive care unit. Results showed that the mean difference between PVP and CVP was 4.4 mmHg (95% CI = 3.7 to 5.0). However, PVP might be 1.9 mmHg below (95% CI = 0.7 to 3.1) or 10.6 mmHg above (95% CI = 9.4 to 11.8) the CVP. The mean difference between changes in PVP and corresponding changes in CVP was 0.3 mmHg (95% CI = -0.1 to 0.7). The actual change in PVP could be 3.0 mmHg below (95% CI = 2.3 to 3.7) or 3.6 mmHg above (95% CI = 2.9 to 4.3) the change in CVP. Overall, the direction of change in PVP (rise or drop) predicted a same direction of change in CVP with an accuracy of 78%. Changes in PVP > or = 2 mmHg predicted a change in same direction of CVP with an accuracy of 90%. The direction of changes in CVP > or = 2 mmHg were predicted by the direction of change in PVP with an accuracy of 91%. We conclude that PVP measurement does not give an accurate estimate of the absolute value of CVP in individual patients. However, as changes in PVP parallel, in direction, changes in CVP, serial measurements of PVP may have a value in determining volume status and guiding fluid therapy in critically ill patients.

Relations between phonological processing abilities and word-level reading skills were examined in a longitudinal correlational study of 216 children. Phonological processing abilities, word-level reading skills, and vocabulary were assessed annually from kindergarten through 4th grade, as the children developed from beginning to skilled readers. Individual differences in phonological awareness were related to subsequent individual differences in word-level reading for every time period examined. Individual differences in serial naming and vocabulary were related to subsequent individual differences in word-level reading initially, but these relations faded with development. Individual differences in letter-name knowledge were related to subsequent individual differences in phonological awareness and serial naming, but there were no relations between individual differences in word-level reading and any subsequent phonological processing ability.

Background: Employee-assistance programs sponsored by companies or labor unions identify workers who abuse alcohol and refer them for care, often to inpatient rehabilitation programs. Yet the effectiveness of inpatient treatment, as compared with a variety of less intensive alternatives, has repeatedly been called into question. In this study, anchored in the work site, we compared the effectiveness of mandatory in-hospital treatment with that of required attendance at the meetings of a self-help group and a choice of treatment options., Methods: We randomly assigned a series of 227 workers newly identified as abusing alcohol to one of three rehabilitation regimens: compulsory inpatient treatment, compulsory attendance at Alcoholics Anonymous (AA) meetings, and a choice of options. Inpatient backup was provided if needed. The groups were compared in terms of 12 job-performance variables and 12 measures of drinking and drug use during a two-year follow-up period., Results: All three groups improved, and no significant differences were found among the groups in job-related outcome variables. On seven measures of drinking and drug use, however, we found significant differences at several follow-up assessments. The hospital group fared best and that assigned to AA the least well; those allowed to choose a program had intermediate outcomes. Additional inpatient treatment was required significantly more often (P less than 0.0001) by the AA group (63 percent) and the choice group (38 percent) than by subjects assigned to initial treatment in the hospital (23 percent). The differences among the groups were especially pronounced for workers who had used cocaine within six months before study entry. The estimated costs of inpatient treatment for the AA and choice groups averaged only 10 percent less than the costs for the hospital group because of their higher rates of additional treatment., Conclusions: Even for employed problem drinkers who are not abusing drugs and who have no serious medical problems, an initial referral to AA alone or a choice of programs, although less costly than inpatient care, involves more risk than compulsory inpatient treatment and should be accompanied by close monitoring for signs of incipient relapse.