Distortions of the Xanthophylls Caused by Interactions with Neighboring Pigments and the LHCII Protein Are Crucial for Studying Energy Transfer Pathways within the Complex.

It has been proposed that photoprotective non-photochemical quenching (NPQ) in higher plants arises from a conformational change in the antenna which alters pigment-pigment interactions. This brings about the formation of energy quenching "traps" that capture and dissipate excitation energy as heat. We have used the semiempirical AM1-CAS-CI method combined with the transition density cube (TDC) approach to model chlorophyll (Chl) to xanthophyll (Xanth) resonant Coulomb couplings in the crystal structure of LHCII. Due to its proposed role as the NPQ quenching site we have focused on lutein interactions and have explored how distortions to lutein conformation, as well as interpigment distances and relative orientations, affect this coupling. Our calculations indicate that distortions as well as Chl-lutein angle have a significant effect on coupling, whereas interpigment distances have a relatively minor effect. We therefore conclude that particular attention to the distortions of the Xanths should be given for calculation of energy transfer pathways and study of the NPQ mechanism.

Fiddling with the pacemaker: Twiddler's syndrome in a Parkinsonian patient.

We describe the case report of an 86-year-old Afro-Caribbean Parkinsonian gentleman with intermittent Mobitz II heart block and syncope who received a DDD pacemaker. Due to Parkinson's syndrome, the patient rotated the atrial lead around the pacemaker, causing the famous "Twiddler's syndrome", a rare clinical issue which can easily be diagnosed with a simple chest X-ray.

Rapid access cardiology--a nine year review.

BACKGROUND: Rapid access cardiology clinics provide a rapid assessment and evaluation of patients with suspected chest pain, heart failure or cardiac arrhythmia. Longitudinal data regarding the attendances and clinical diagnoses at rapid access clinics is lacking and may provide insight into their efficiency and role in providing a comprehensive referral service for primary care. METHODS: Data regarding total number of attendances and diagnoses were retrospectively analysed from databases collated by nurse specialists and physicians undertaking rapid access clinics at Charing Cross Hospital between April 2002 and March 2011. RESULTS: A total of 12 000 patients were seen over the 9-year time period. Demand for Rapid Access Chest Pain Clinic and Rapid Access Arrhythmia Clinic has shown a steady rise since 2007 whereas attendances at Rapid Access Heart Failure Clinic have remained constant. The proportion of patients diagnosed with significant cardiac disease across all rapid access clinics has not changed significantly. The most commonly diagnosed arrhythmia was atrial fibrillation (15% of all attendances). CONCLUSION: Referrals have increased to our service which suggests that demand for a rapid access cardiology service remains high and the proportion of patients diagnosed with significant cardiac disease has remained constant. Despite considerable motivation towards providing primary based care this has not occurred in our local area and we believe this shows that our model, based in secondary care to be both efficient and accessible to local GPs and patients.

Recommendations for transoesophageal echocardiography: update 2010.

Transoesophageal echocardiography (TOE) is a standard and indispensable technique in clinical practice. The present recommendations represent an update and extension of the recommendations published in 2001 by the Working Group on Echocardiography of the European Society of Cardiology. New developments covered include technical advances such as 3D transoesophageal echo as well as developing applications such as transoesophageal echo in aortic valve repair and in valvular interventions, as well as a full section on perioperative TOE.

Brain natriuretic peptide testing for angina in a rapid-access chest pain clinic.

BACKGROUND: Patients complaining of chest pain are frequently referred to secondary care, although the majority have pain of non-cardiac origin. AIM: To investigate whether B-type natriuretic peptide (BNP) levels are predictive of a diagnosis of non-cardiac pain. DESIGN: Cross-sectional study. METHODS: Consecutive patients (n = 296) presenting to a rapid-access chest pain clinic (RACPC) received the usual clinical assessment plus near-patient BNP testing, with the assessor blinded to the result. After clinical assessment (including exercise stress testing if clinically indicated), pain was diagnosed likely/definitely cardiac or non-cardiac. RESULTS: Median BNP was higher in those diagnosed with likely/definite cardiac chest pain (26.5 vs. 8 pg/ml) (p < 0.0001, Wilcoxon rank sum test). The odds ratio for cardiac pain in those with BNP <20 pg/ml was 0.25 (95%CI 0.14-0.47) (p < 0.0005); adjusting for age and sex reduced this to 0.41 (95%CI 0.20-0.83) (p = 0.01). The area under the curve (AUC) for the model including BNP, age and sex was 0.70. With BNP as a continuous variable, the AUC for the same model was 0.72. DISCUSSION: In typical patients presenting to a RACPC, those with a BNP < or =20 pg/ml were significantly less likely to be diagnosed with cardiac pain. Near-patient BNP testing may have a role as a 'rule out test' for angina in patients presenting to a RACPC.

Contemporary mortality due to acute myocardial infarction, unstable angina and exertional angina in a population in South East London.

BACKGROUND: Data on the contemporary mortality of coronary heart disease (CHD) are surprisingly sparse. AIM: To describe the contemporary mortality of all manifestations of CHD. DESIGN: Prospective follow-up of patients with a first presentation of CHD in a defined population. METHODS: We studied 537 patients with a first presentation of acute myocardial infarction, unstable angina or new exertional angina in Bromley Health Authority, London (population 295,000). Patients were prospectively monitored for cardiac and non-cardiac mortality for a median of 6 years. RESULTS: During a median 6 years follow-up, there were 88 (16%) deaths. Survival free from cardiac death was not significantly different between unstable angina (92%) and new exertional angina (94%), but was lower for acute myocardial infarction (84%). DISCUSSION: Mortality from CHD appears to be falling. However, efforts to prevent myocardial infarction should continue to be a priority, because on-going early mortality remains high. New exertional angina should be diagnosed and managed promptly, as its mortality is similar to that of unstable angina.

A rapid access cardiology service for chest pain, heart failure and arrhythmias accurately diagnoses cardiac disease and identifies patients at high risk: a prospective cohort study.

OBJECTIVE: To conduct a one year follow up study of patients seen in a combined rapid access chest pain, arrhythmia and heart failure clinic. METHODS: Local general practitioners, accident and emergency department clinicians and other hospital clinicians were invited to refer patients with a new presentation of chest pain, palpitations and suspected cardiac-induced breathlessness to the rapid access cardiology clinics at Charing Cross Hospital, London, on a one-stop, no appointment basis. Consent to be followed up by a postal questionnaire one year later was sought from all patients attending between 1 November 2002 and 31 October 2003. RESULTS: 1223 patients were seen in the 12 month study period. 940 (77%) consented to one year follow up. 216 (23%) patients had a diagnosis of definite cardiac, 621 (66%) of not cardiac and 103 of possible cardiac disease (11%). 98% of patients diagnosed "not cardiac" did not receive a diagnosis of cardiac disease over the following 12 months. Of patients with diagnosed definite cardiac disease, one year cardiac mortality was 7 of 216 (3%), compared with an age- and sex-matched expected cardiac mortality of 0.9% (standardised mortality ratio 3.5, 95% confidence interval (CI) 1.4 to 7.2). For patients with an initial diagnosis of possible or not cardiac disease, cardiac mortality at one year was 0.3% compared with an expected cardiac mortality of 0.4% (standardised mortality ratio 0.8, 95% CI 0.1 to 2.8). CONCLUSIONS: A rapid access cardiology clinic accurately diagnoses and risk stratifies patients into those with cardiac disease at high risk of cardiac death and those without significant cardiac disease.

Echocardiographic features and brain natriuretic peptides in patients presenting with heart failure and preserved systolic function.

OBJECTIVE: To characterise patients who appear to fulfil the diagnosis of heart failure with preserved systolic function clinically, echocardiographically, and by concentrations of brain-type natriuretic peptide (BNP). METHODS: 102 new cases of heart failure were identified over 24 months in 213 patients referred to a rapid access heart failure clinic. Patients with heart failure and preserved systolic function with contemporary markers of diastolic function were assessed to evaluate their cardiac status further. RESULTS: Forty patients (39%) had an ejection fraction (EF) < 45% and 62 (61%) had an EF > or = 45%. Of these 62 patients, 30 (48%) fulfilled the case definition of diastolic heart failure. The remaining 32 (52%) had neither an EF < 45% nor abnormalities of diastolic function. Dobutamine stress echocardiography was performed on 26 (42%) patients with EF > or = 45%, which provided an alternative explanation for symptoms in 15 (58%) patients. Concentrations of BNP were higher in patients with diastolic abnormalities (mean (SEM) 101.4 (32.5) pg/ml v 58.4 (6.78) pg/ml, p = 0.042) and with no diastolic abnormalities (199 (37.9) pg/ml v 58.4 (6.78) pg/ml, p < 0.0001) than in patients with no heart failure. CONCLUSION: Among ambulatory patients presenting with suspected heart failure in the community 19% have systolic dysfunction, 14% have diastolic dysfunction, and 15% seemingly have heart failure with neither systolic nor diastolic dysfunction. A new understanding, including alternative parameters of diastolic function, seems to be necessary to classify patients with heart failure and preserved systolic function.

Usage of troponin in the real world: a lesson for the introduction of biochemical assays.

BACKGROUND: Studies have demonstrated economic and clinical effectiveness using troponin as a risk stratification tool in chest pain patients. Those with a positive result are investigated invasively, whilst those with a negative result and ECG are promptly mobilized, facilitating discharge. AIM: To determine whether our use of troponin I (cTnI) in routine clinical practice conforms to ideal standards. DESIGN: Audit study. METHODS: Data were collected from 93 laboratory request forms for cTnI measurement on 72 patients with matched available patient records. RESULTS: Eighty requests had no information regarding timing of blood sample in relation to the clinical event; 39% gave no clinical indication. Only 71% of results were available within 12 h. An admission diagnosis of acute coronary syndrome (ACS) was made in 25%. Fifteen had typical cardiac chest pain with a negative cTnI: 6 of these had an exercise treadmill test before discharge. Nine had a positive cTnI, but only two had coronary angiography. Of patients with negative cTnI and possible ACS, 84% were in hospital for >4 days. DISCUSSION: The introduction of troponin assays into widespread use requires careful assessment. cTnI requests and subsequent patient management remain below expected standards. Ideally, the laboratory should provide an accurate result within a reasonable time frame, while physicians need to request cTnI at a suitable time-point and use the result appropriately. Lessons from the introduction of cTnI measurement may be useful for the introduction of future new tests in other areas of cardiology and medicine.

Rapid access arrhythmia clinic for the diagnosis and management of new arrhythmias presenting in the community: a prospective, descriptive study.

OBJECTIVE: To investigate whether a rapid access approach is useful for the evaluation of patients with symptoms suggestive of a new cardiac arrhythmia. DESIGN: Prospective, descriptive study. SETTING: Secondary care based rapid access arrhythmia clinic in West London, UK. PARTICIPANTS: Patients referred by their general practitioner or the emergency department with symptoms suggestive of a new cardiac arrhythmia. MAIN OUTCOME MEASURES: Number of patients with a newly diagnosed significant arrhythmia. Number of patients with diagnosed atrial fibrillation. Number of eligible, moderate, and high risk patients treated with warfarin. RESULTS: Over a 25 month period 984 referrals were assessed. The mean age was 55 years (range 20-90 years) and 56% were women. The median time from referral to assessment was one day. A significant cardiac arrhythmia was newly diagnosed in 40% of patients referred to the RAAC. The most common arrhythmia was atrial fibrillation, with 203 new cases (21%). Of these, 74% of eligible patients over 65 were treated with warfarin. Other arrhythmias diagnosed were supraventricular tachycardias (127 (13%)), conduction disorders (43 (4%)), and non-sustained ventricular tachycardia (21 (2%)). Vasovagal syncope was diagnosed for 53 patients (5%). The most frequent diagnosis was symptomatic ventricular and supraventricular extrasystoles (355 (36%)). CONCLUSION: A rapid access arrhythmia clinic is an innovative approach to the diagnosis and management of new cardiac arrhythmias in the community. It provides a rapid diagnosis, stratifies risk, and leads to prompt initiation of effective treatment for this population.

Hospitalization of patients with heart failure: a population-based study.

AIMS: To describe the clinical course of heart failure in a population-based sample of incident cases, and to identify factors predicting hospitalization and mortality. METHODS AND RESULTS: Three hundred and thirty-two incident cases were identified over 15 months; 208 inpatients and 124 outpatients. Thirty-eight inpatients died during the first hospital admission (case fatality 18%) leaving 294 at risk of subsequent hospitalization. Over an average follow-up of 19 months, 173 cases were hospitalized on 311 occasions. Two hundred and twenty-four (72%) of these admissions were unplanned, with 51% due to worsening heart failure. One hundred and ten cases died over the same period. Cases diagnosed as an inpatient had 26 more admissions for worsening heart failure per 100 cases during follow-up (95% CI 9 to 44) compared to cases diagnosed as an outpatient, and also a higher mortality (hazard ratio 3.1 (95% CI 1.9 to 5.1)). Age was the only factor associated with an increased risk of hospitalization for worsening heart failure, but age, functional class and serum creatinine were predictive of mortality. CONCLUSIONS: New cases of heart failure are at high risk of subsequent hospitalization, especially during the first months after diagnosis. Whilst predicting which patients will be hospitalized is difficult, interventions designed to reduce hospitalizations for worsening heart failure should be targeted at elderly inpatients with a new diagnosis.

Variation in 16S-23S rRNA intergenic spacer regions among Bacillus subtilis 168 isolates.

The genome of the Bacillus subtilis 168-type strain contains 10 ribosomal RNA (rRNA) operons. In the intergenic spacer region (ISR) between the 16S and 23S rRNA genes, five rRNA operons, rrnI-H-G and rrnJ-W, lack a trinucleotide signature region. Precise determination of molecular weight (MW), using electrospray mass spectrometry (MS), of the polymerase chain reaction (PCR) products from a segment of the ISR from the 168-type strain and B. subtilis 168-like strain 23071 demonstrated 114 and 111 basepair (bp) PCR products (due to the presence or absence of the insert in the operons) as predicted from sequence. However, PCR of the ISR segment for five other B. subtilis 168 isolates generated only a 114 bp PCR product, suggesting the presence of the trinucleotide signature region in all rRNA operons for these strains. Additional genetic variability between the seven B. subtilis 168 isolates was demonstrated by restriction fragment length polymorphism (RFLP) of the rRNA operons, with three distinct patterns found upon Southern blot analysis. The 168-type strain and three others (23066, 23067, and 23071) exhibited the same Southern pattern. Thus, operon deletion is not responsible for the absence of a 111 bp product on MS analysis for strains 23066 and 23067. Restriction analysis confirmed the presence of the trinucleotide signature region in the ISR of all rRNA operons for five B. subtilis 168 isolates; sequencing of rrnW/H from a representative strain also upheld this finding. These results help provide a better understanding of variations in sequence, operon number and chromosomal organization, both within a genome and among isolates of B. subtilis subgroup 168. It is also hypothesized that the presence of the trinucleotide insert in certain rRNA operons may play a role in rRNA maturation and protein synthesis.

Genotyping single nucleotide polymorphisms using intact polymerase chain reaction products by electrospray quadrupole mass spectrometry.

Both single nucleotide polymorphisms (SNPs) and mutations are commonly observed in the gene encoding the tumor suppressor protein, p53. SNPs occur at specific locations within genes whereas mutations may be distributed across large regions of genes. When determining nucleotide differences, mass spectrometry is the only method other than Sanger sequencing which offers direct structural information. Electrospray ionization (ESI) quadrupole mass spectrometry (MS) analysis of intact polymerase chain reaction (PCR) products was performed following a simple purification and on-line heating to limit ion adduction. The PCR products were amplified directly from genomic DNA rather than plasmids, as in our previous work. Two known polymorphisms of the p53 gene were genotyped. A cytosine (C) or guanine (G) transversion, designated C <--> G (G <--> C on the opposite strand), were each detected by a 40.0 Da change upon ESI quadrupole MS analysis. Using known PCR products as standards, the genotypes determined for 10 human samples corresponded with restriction fragment length polymorphism (RFLP) analysis. Cytosine/thymine (T) transitions, designated C <--> T (G <--> A on the opposite strand), were also genotyped by ESI-MS. This SNP is discriminated by a 15.0 Da change on one strand (C <--> T) and a 16.0 Da change on the other (G <--> A). Appropriate sample preparation and instrumental configuration (including heated sample inlet syringe and MS source), to limit adducts, are both vital for successful ESI quadrupole MS analysis of intact PCR products.