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2.  Clinical features in a family with an R460H mutation in transforming growth factor β receptor 2 gene 
Journal of Medical Genetics  2006;43(12):908-916.
Objectives
To describe the clinical findings and natural history in 22 carriers of an R460H mutation in the transforming growth factor β receptor 2 gene (TGFβR2) from a five‐generation kindred ascertained by familial aortic dissection.
Methods
13 of the confirmed carriers were interviewed and examined, and information about the remaining carrier was obtained from medical records. Clinical information about deceased individuals was obtained, when possible, from postmortem reports, death certificates and medical records.
Results
There have been eight sudden deaths; the cause of death was aortic dissection in all six cases in which a postmortem examination was performed. Three individuals had undergone aortic replacement surgery. Dissection had occurred throughout the aorta, and in one case in the absence of aortic root dilatation. Subarachnoid haemorrhage, due to a ruptured berry aneurysm, had occurred in two individuals. Four gene carriers and one deceased family member who were investigated had tortuous cerebral blood vessels. One had tortuous vertebral arteries, two had tortuous carotid arteries and one a tortuous abdominal aorta. Two individuals were found to have a brachiocephalic artery aneurysm and a subclavian artery aneurysm, respectively.
Conclusions
Despite the predisposition to aortic dilatation and dissection, individuals did not frequently manifest the skeletal features of Marfan syndrome, with the exception of joint hypermobility. No one individual had ocular lens dislocation. Striae and herniae were common. There was some overlap with Ehlers–Danlos syndrome type 4, OMIM 130050, with soft translucent skin, which is easily bruised. Other features were arthralgia, migraine and a tendency to fatigue easily, varicose veins and prominent skin striae. This family provides further evidence that mutations in TGFβR2 cause a distinct syndrome that needs to be distinguished from Marfan syndrome to direct investigation and management of patients and shows the natural history, spectrum of clinical features and variable penetrance of this newly recognised condition.
doi:10.1136/jmg.2006.042176
PMCID: PMC2563201  PMID: 16885183
3.  Undertreatment of coronary heart disease in patients undergoing coronary artery bypass surgery 
Heart  2006;92(5):697-698.
doi:10.1136/hrt.2005.069914
PMCID: PMC1860953  PMID: 16614294
coronary heart disease; coronary artery bypass surgery; prevention
4.  Septic emboli from aortic valve endocarditis 
Heart  2004;90(8):865.
doi:10.1136/hrt.2003.029447
PMCID: PMC1768351  PMID: 15253954
Images in cardiology
5.  Improving the positive predictive value of exercise testing in women 
Heart  2003;89(12):1416-1421.
Objective: To identify exercise test variables that can improve the positive predictive value of exercise testing in women.
Design: Cohort study.
Setting: Regional cardiothoracic centre.
Subjects: 1286 women and 1801 men referred by primary care physicians to a rapid access chest pain clinic, of whom 160 women and 406 men had ST depression of at least 1 mm during exercise testing. The results for 136 women and 124 men with positive exercise tests were analysed.
Main outcome measures: The proportion of women with a positive exercise test who could be identified as being at low risk for prognostic coronary heart disease and the resulting improvement in the positive predictive value.
Results: Independently of age, an exercise time of more than six minutes, a maximum heart rate of more than 150 beats/min, and an ST recovery time of less than one minute were the variables that best identified women at low risk. One to three of these variables identified between 11.8% and 41.2% of women as being at low risk, with a risk for prognostic disease of between 0−11.5%. The positive predictive value for the remaining women was improved from 47.8% up to 61.5%, and the number of normal angiograms was potentially reducible by between 21.1−54.9%. By the same criteria, men had higher risks for prognostic disease.
Conclusions: A strategy of discriminating true from false positive exercise tests is worthwhile in women but less successful in men.
PMCID: PMC1767962  PMID: 14617551
women; exercise testing; coronary heart disease; atherosclerosis; ST recovery time
6.  Echocardiography 2003 
Heart  2003;89(Suppl 3):iii1-.
doi:10.1136/heart.89.suppl_3.iii1
PMCID: PMC1876305
7.  Epistatic interaction between variations in the angiotensin I converting enzyme and angiotensin II type 1 receptor genes in relation to extent of coronary atherosclerosis 
Heart  2003;89(10):1195-1199.
Objective: To test the hypothesis that gene–gene interaction of the renin–angiotensin system is associated with an effect on the extent of coronary atherosclerosis.
Setting and results: A cohort of 1162 patients with coronary artery disease were genotyped for genetic polymorphisms in the renin–angiotensin system. Patients carrying the D allele of the angiotensin I converting enzyme (ACE) gene had greater coronary extent scores (defined as the number of coronary segments with 5% to 75% stenosis) than those not carrying this allele (p = 0.006 in non-parametric analysis and p = 0.019 in parametric analysis). This association remained significant after adjusting for age, body mass index, hypertension, and diabetes, which were also significantly associated with coronary extent scores. There was a significant interaction (p = 0.033) between genotypes of ACE and angiotensin II type 1 receptor (AGTR1). The association between the ACE gene D allele and increased coronary extent scores was significant (p = 0.008 in non-parametric and p = 0.027 in parametric analysis) in those carrying the +1166 C allele of the AGTR1 gene, but was absent in those not carrying the AGTR1 gene +1166 C allele.
Conclusion: These findings suggest that variation in the ACE and AGTR1 genes and their interaction may not only contribute to susceptibility of coronary artery disease as previously found but also modify the disease process, thus contributing to interindividual differences in severity of the disease.
PMCID: PMC1767923  PMID: 12975417
renin; angiotensin system; genetic polymorphism; gene; gene interaction; coronary artery disease
8.  Inhibition of temporary pacing by a mobile phone 
Heart  2002;87(2):130.
PMCID: PMC1766997  PMID: 11796548
Images in cardiology
9.  Sex differences in investigation results and treatment in subjects referred for investigation of chest pain 
Heart  2001;85(2):149-152.
OBJECTIVE—To evaluate differences in investigation results and treatment between men and women referred for diagnostic treadmill exercise testing and coronary arteriography.
DESIGN—Cohort study.
SETTING—Tertiary cardiology centre.
SUBJECTS—1522 subjects referred by primary care physicians to an open access chest pain clinic for initial investigation of chest pain, of whom 485 were subsequently referred for coronary arteriography; and a similar cohort of 107 subjects referred directly by secondary care physicians for diagnostic coronary arteriography.
MAIN OUTCOME MEASURES—Rates of positive exercise tests and rates for referral for arteriography and revascularisation according to sex.
RESULTS—Overall, women were less likely to be referred for arteriography and revascularisation than men. However, men were more likely to have positive exercise tests, and for various exercise test diagnostic end points men were also more likely to have significant coronary artery disease. After taking this into account, there was no sex difference in referral rates for arteriography or revascularisation.
CONCLUSIONS—There was no evidence of a sex bias resulting in inappropriate underinvestigation or undertreatment of women. However, the positive predictive value of treadmill exercise testing is low for women and further research is needed into how best to investigate women with chest pain.


Keywords: sex differences; exercise test; chest pain
doi:10.1136/heart.85.2.149
PMCID: PMC1729612  PMID: 11156662
10.  Recurrent pericardial effusion: the value of polymerase chain reaction in the diagnosis of tuberculosis 
Heart  1999;82(2):246-247.
A 23 year old army man presented with progressive dyspnoea and was found to have a massive pericardial effusion. Despite extensive investigations the cause remained elusive, until samples were sent for polymerase chain reaction (PCR). This case was unusual for several reasons and is a reminder of the atypical way in which tuberculosis infection can present and how a high index of suspicion should be maintained. It shows the importance of molecular biological advances in providing simple and rapid methods for arriving at the correct diagnosis, by way of nucleic acid probes and polymerase chain reaction. 

PMCID: PMC1729120  PMID: 10409547
11.  Intracoronary Multi-link stents: experience in 218 patients using aspirin alone 
Heart  1998;80(5):499-504.
Objectives—To assess procedural outcome, complications, and clinical follow up in 218 patients who underwent treatment with 297 Multi-link (Guidant) stents implanted without the use of intravascular ultrasound (IVUS) or quantitative coronary angiography (QCA), and using aspirin alone as antiplatelet therapy.
Methods—The case records and angiograms were reviewed and the patients were contacted by telephone to determine their symptoms and any adverse events at follow up. Data were analysed using Fisher's exact test. 
Results—Of the 218 patients included in the study, 45 had multivessel intracoronary intervention, and 55 had unstable angina. The mean (SD) length of hospital stay following the procedure was 2.0 (2.1) days. There were two early deaths at less than 30 days, and two deaths during follow up at more than 100 days. Ten patients suffered complications during the first 30 days: four had subacute stent thrombosis, of whom two died and two were treated successfully with coronary artery bypass grafting; five had a non-Q wave myocardial infarction; and one had a femoral false aneurysm. Patient outcome was analysed according to stent diameter (3.0 mm or less, or 3.5 mm or more) and by angina status (stable or unstable). In patients in whom at least one stent was 3.0 mm diameter, four of 86 patients suffered acute stent occlusion, whereas in the 132 patients in whom all stents were at least 3.5 mm diameter there were no cases of stent occlusion (p = 0.02). In the unstable angina group two of 55 patients suffered acute stent occlusion compared to two of 163 patients in the stable angina group (NS). In patients with unstable angina and at least one stent of 3.0 mm diameter, the acute occlusion rate was 7.1% (two of 28 patients). Three of the four patients with stent occlusion had undergone complex procedures. Twenty eight patients were restudied for recurrent symptoms during the follow up period. Of these, eight patients had restenosis within their stent. In seven of these patients the stent size was 3.0 mm diameter, and in the remaining patient the stent size was 4.0 mm diameter. Three of the 28 patients restudied had developed new disease remote from the stented site, and 17 had patent stents and no significant other coronary lesion. 
Conclusions—This study suggests that coronary intervention using the Multi-link stent is safe and effective using aspirin alone, without IVUS or QCA, when stent diameter is greater than 3.0 mm. All cases of stent occlusion in this series occurred in patients in whom at least one stent was 3.0 mm diameter, with stent occlusion being higher in patients with unstable angina compared to those with stable angina. Additional antiplatelet therapy may be beneficial in those patients in whom Multi-link stent diameter is less than 3.5 mm, particularly in those with unstable angina, but is not necessary for patients receiving Multi-link stents of 3.5 mm diameter or greater.

 Keywords: intracoronary Multi-link stents;  aspirin;  stent occlusion
PMCID: PMC1728838  PMID: 9930052
13.  Biochemical diagnosis of ventricular dysfunction in elderly patients in general practice: observational study 
BMJ : British Medical Journal  2000;320(7239):906-908.
Objective
To investigate the usefulness of measuring plasma concentrations of B type natriuretic peptide in the diagnosis of left ventricular systolic dysfunction in an unselected group of elderly people.
Design
Observational study.
Setting
General practice with four centres in Poole, Dorset.
Participants
155 elderly patients aged 70 to 84 years.
Main outcome measures
Diagnostic characteristics of plasma B type natriuretic peptide measured by radioimmunoassay as a test for left ventricular systolic dysfunction assessed by echocardiography.
Results
The median plasma concentration of B type natriuretic peptide was 39.3 pmol/l in patients with left ventricular systolic dysfunction and 15.8 pmol/l in those with normal function. The proportional area under the receiver operator curve was 0.85. At a cut-off point of 18.7 pmol/l the test sensitivity was 92% and the predictive value 18%.
Conclusions
Plasma concentration of B type natriuretic peptide could be used effectively as an initial test in a community screening programme and, possibly, using a low cut-off point, as a means of ruling out left ventricular systolic dysfunction. It is, however, not a good test to “rule in” the diagnosis, and access to echocardiography remains essential for general practitioners to diagnose heart failure early.
PMCID: PMC27331  PMID: 10741999
14.  Prevalence and clinical characteristics of left ventricular dysfunction among elderly patients in general practice setting: cross sectional survey 
BMJ : British Medical Journal  1999;318(7180):368-372.
Objective
To assess the prevalence and clinical characteristics of left ventricular dysfunction among elderly patients in the general practice setting by echocardiographic assessment of ventricular function.
Design
Cross sectional survey.
Setting
Four centre general practice in Poole, Dorset.
Subjects
817 elderly patients aged 70-84 years.
Main outcomes
Echocardiographic assessment of left ventricular systolic function including measurement of ejection fraction by biplane summation method where possible, clinical symptoms, and signs of left ventricular dysfunction.
Results
The overall prevalence of left ventricular systolic dysfunction was 7.5% (95% confidence interval 5.8% to 9.5%); mild dysfunction (5.0%) was considerably more prevalent than moderate (1.6%) or severe dysfunction (0.7%). Measurement of ejection fraction was possible in 82% of patients (n=667): in patients categorised as having mild, moderate, or severe dysfunction, the mean ejection fraction was 48% (SD 12.0), 38% (8.1), and 26% (7.9) respectively. At all ages the prevalence was much higher in men than in women (odds ratio 5.1, 95% confidence interval 2.6 to 10.1). No clinical symptom or sign was both sensitive and specific. In around half the patients with ventricular dysfunction (52%, 32/61) heart failure had not been previously diagnosed.
Conclusions
Unrecognised left ventricular dysfunction is a common problem in elderly patients in the general practice setting. Appropriate treatment with angiotensin converting enzyme inhibitors has the potential to reduce hospitalisation and mortality in these patients, but diagnosis should not be based on clinical history and examination alone. Screening is feasible in general practice, but it should not be implemented until the optimum method of identifying left ventricular dysfunction is clarified, and the cost effectiveness of screening has been shown.
Key messagesLeft ventricular dysfunction detected by echocardiography is common in elderly peopleMen are much more likely to be affected than womenThe accuracy of clinical diagnosis is very limited in this age groupMany patients who would benefit from treatment remain undetected
PMCID: PMC27725  PMID: 9933201
15.  Visualisation of extensive water ribbons and networks in a DNA minor-groove drug complex. 
Nucleic Acids Research  1998;26(12):2873-2878.
The crystal structure is reported of a complex between an ethyl derivative of the minor-groove drug furamidine and the dodecanucleotide duplex d(CGCGAATTCGCG)2, which has been refined to 1.85 A resolution and an R factor of 16.6% for data collected at -173 degreesC. An exceptionally large number (220) of water molecules have been located. The majority of these occur in the first coordination shell of solvation. There are extensive networks of connected waters, both in the major and minor grooves. In particular, there are 21 water molecules associated with the minor-groove drug, via hydrogen bonds from the four charged nitrogen atoms. One cluster of four waters is situated in the groove itself; the majority are on the outer edge of the groove, and serve to bridge between the outward-directed drug nitrogen atoms and backbone phosphate oxygen atoms. These bridges are both intra- and inter-strand, with the net effect that the outer edge of the drug molecule is covered by ribbons of water molecules.
PMCID: PMC147633  PMID: 9611230
16.  Effects of Following National Committee for Clinical Laboratory Standards and Deutsche Industrie Norm-Medizinische Mikrobiologie Guidelines, Country of Isolate Origin, and Site of Infection on Susceptibility of Escherichia coli to Amoxicillin-Clavulanate (Augmentin) 
Journal of Clinical Microbiology  1998;36(5):1361-1365.
Amoxicillin-clavulanate (Augmentin), as a combination of two active agents, poses extra challenges over single agents in establishing clinically relevant breakpoints for in vitro susceptibility tests. Hence, reported differences in amoxicillin-clavulanate percent susceptibilities among Escherichia coli isolates may reflect localized resistance problems and/or methodological differences in susceptibility testing and breakpoint criteria. The objectives of the present study were to determine the effects of (i) methodology, e.g., those of the National Committee for Clinical Laboratory Standards (NCCLS) and the Deutsche Industrie Norm-Medizinische Mikrobiologie (DIN), (ii) country of origin (Spain, France, and Germany), and (iii) site of infection (urinary tract, intra-abdominal sepsis, or other site[s]) upon the incidence of susceptibility to amoxicillin-clavulanate in 185 clinical isolates of E. coli. Cefuroxime and cefotaxime were included for comparison. The use of NCCLS methodology resulted in different distribution of amoxicillin-clavulanate MICs than that obtained with the DIN methodology, a difference highlighted by the 10% more strains found to be within the 8- to 32-μg/ml MIC range. This difference reflects the differing amounts of clavulanic acid present. NCCLS and DIN methodologies also produce different MIC distributions for cefotaxime but not for cefuroxime. Implementation of NCCLS and DIN breakpoints produced markedly different incidences of strains that were found to be susceptible, intermediate or resistant to amoxicillin-clavulanate. A total of 86.5% strains were found to be susceptible to amoxicillin-clavulanate by the NCCLS methodology, whereas only 43.8% were found to be susceptible by the DIN methodology. Similarly, 4.3% of the strains were found to be resistant by NCCLS guidelines compared to 21.1% by the DIN guidelines. The use of DIN breakpoints resulted in a fivefold-higher incidence of strains categorized as resistant to cefuroxime. There were no marked differences due to country of origin upon the MIC distributions for amoxicillin-clavulanate, cefuroxime, or cefotaxime, as determined with the NCCLS guidelines. Isolates from urinary tract and intra-abdominal infections were generally more resistant to amoxicillin-clavulanate than were isolates from other sites of infection.
PMCID: PMC104829  PMID: 9574706
17.  The midcycle increase in ovarian glucose uptake is associated with enhanced expression of glucose transporter 3. Possible role for interleukin-1, a putative intermediary in the ovulatory process. 
This study characterizes the rat ovary as a site of hormonally dependent glucose transporter (Glut) expression, and explores the potential role of interleukin (IL)-1, a putative intermediary in the ovulatory process, in this regard. Molecular probing throughout a simulated estrous cycle revealed a significant surge in ovarian Glut3 (but not Glut1) expression at the time of ovulation. Treatment of cultured whole ovarian dispersates from immature rats with IL-1beta resulted in upregulation of the relative abundance of the Glut1 (4.5-fold) and Glut3 (3.5-fold) proteins as determined by Western blot analysis. Other members of the Glut family (i.e., Gluts 2, 4, and 5) remained undetectable. The ability of IL-1 to upregulate Glut1 and Glut3 transcripts proved time-, dose-, nitric oxide-, and protein biosynthesis-dependent but glucose independent. Other ovarian agonists (i.e., TNF alpha, IGF-I, interferon-gamma, and insulin) were without effect. Taken together, our findings establish the mammalian ovary as a site of cyclically determined Glut1 and Glut3 expression, and disclose the ability of IL-1 to induce the ovarian expression as well as translation of Glut1 and Glut3 (but not of Gluts 2, 4, or 5). Our observations also establish IL-1 as the first known regulator of Glut3, the most efficient Glut known to date. In so doing, IL-1, a putative component of the ovulatory process, may be acting to meet the increased metabolic demands imposed on the growing follicle and the ovulated cumulus-enclosed oocyte.
PMCID: PMC508060  PMID: 9151802
18.  Repertoire of transcribed peripheral blood T-cell receptor beta chain variable-region genes in acute rheumatic fever. 
Infection and Immunity  1996;64(7):2842-2845.
Patients with severe group A streptococcal infections have abnormalities in the Vbeta repertoire of peripheral blood T cells that are consistent with superantigen stimulation by cytoplasmic membrane proteins. The purpose of this study was to determine whether similar changes in Vbeta repertoire could be found for patients with acute rheumatic fever (ARF). The mean Vbeta repertoire of peripheral blood T cells in nine hospitalized ARF patients was similar to that of 34 controls and did not change during 6 months of follow-up in 6 of the ARF subjects. We were unable to detect changes in the Vbeta repertoire of peripheral blood T cells from patients with ARF that could be attributed to the influence of a superantigen.
PMCID: PMC174152  PMID: 8698521
19.  Human immunodeficiency virus type 1 infection of H9 cells induces increased glucose transporter expression. 
Journal of Virology  1996;70(10):7275-7279.
A clone obtained from a differential display screen for cellular genes with altered expression during human immunodeficiency virus (HIV) infection matched the sequence for the human GLUT3 facilitative glucose transporter, a high-velocity-high-affinity facilitative transporter commonly expressed in neurons of the central nervous system. Northern (RNA) analysis showed that GLUT3 expression increased during infection. Flow cytometry showed that GLUT3 protein expression increased specifically in the HIV-infected cells; this increase correlated with increased 2-deoxyglucose transport in the HIV-infected culture. HIV infection therefore leads to increased expression of a glucose transporter normally expressed at high levels in other cell types and a corresponding increase in glucose transport activity. If HIV infection places increased metabolic demands on the host cell, changes in the expression of a cellular gene that plays an important role in cellular metabolism might provide a more favorable environment for viral replication.
PMCID: PMC190788  PMID: 8794382
20.  Evaluation of mupirocin E-test for determination of isolate susceptibility: comparison with standard agar dilution techniques. 
Journal of Clinical Microbiology  1995;33(9):2254-2259.
Mupirocin E-test strips have been evaluated for their ease of use and accuracy in determining the susceptibilities of 171 strains of Staphylococcus spp., Streptococcus spp., Haemophilus influenzae, and Moraxella catarrhalis. The susceptibility of each strain was determined on two occasions, using parallel E-test and agar dilution methodologies each time. To ensure similar precisions for statistical analyses, E-test MICs were rounded up to a standard twofold agar dilution scale. Clear, elliptical zones were obtained against Staphylococcus spp. M. catarrhalis also gave clear zones, but the scale intercept was often difficult to interpret because of the irregular shape of the inhibition zone. Poor growth sometimes resulted in less-distinct zones of inhibition against Streptococcus spp. and H. influenzae. Excellent correlation was observed between the the E-test and agar dilution against Staphylococcus spp. and H. influenzae, with > 95% of the E-test values falling within one log2 dilution of the corresponding agar MIC. The correlation was lower for Streptococcus spp. and M. catarrhalis, with 86 and 83%, respectively, of E-test results falling within one log2 dilution of the agar MIC. When E-test MICs did not agree exactly with the corresponding agar MIC against Staphylococcus spp. or Streptococcus spp., there was a tendency for the E-test to give a lower MIC. This bias has little effect upon individual MICs in staphylococci or in the generation of susceptibility interpretation errors ( < 1.5% overall), but it could reduce population geometric mean MICs by factors of 0.78 to 0.83.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC228389  PMID: 7494011
22.  Total atrial paralysis after permanent dual chamber cardiac pacing. 
British Heart Journal  1993;69(2):191-192.
A 73 year old woman with known ischaemic heart disease and ischaemic ventricular tachycardia underwent temporary dual chamber pacing as part of the treatment to suppress tachycardia. Insertion of a permanent dual chamber system seven days later was uncomplicated. Total atrial paralysis, with inability to pace the atrium or obtain an atrial electrocardiogram from four atrial sites, developed within 24 hours of the permanent system being implanted. Atrial electrical and mechanical function recovered over several weeks.
Images
PMCID: PMC1024951  PMID: 8435248
23.  Cardiovascular manifestations of Marfan's syndrome: improved evaluation by transoesophageal echocardiography. 
British Heart Journal  1993;69(2):104-108.
OBJECTIVES--To assess the value of transoesophageal echocardiography in patients with Marfan syndrome particularly those with suspected aortic pathology or where conventional transthoracic imaging was suboptimal. DESIGN AND PATIENTS--Eleven patients with Marfan syndrome. Seven patients were studied because of suspected aortic dissection and four because of inadequate transthoracic imaging. INTERVENTION--Transoesophageal echocardiography and colour Doppler flow mapping by a 5 MHz single plane transoesophageal probe. RESULTS--Aortic dissection was identified in six patients with subsequent diagnostic confirmation in all six. No dissection was found in one patient in whom the diagnosis had been suspected clinically. Estimates of aortic root dimensions and assessment of aortic and mitral valve pathology were made in four other patients with inadequate transthoracic imaging. CONCLUSIONS--Transoesophageal echocardiography provides rapid diagnostic information in patients with Marfan syndrome with suspected aortic dissection and enhances the assessment of cardiovascular manifestations of this condition.
Images
PMCID: PMC1024934  PMID: 8435233
24.  Pericardial haemorrhage causing right atrial compression after cardiac surgery: role of transoesophageal echocardiography. 
British Heart Journal  1991;65(6):355-356.
After cardiac surgery transoesophageal echocardiography showed a large thrombus compressing the right atrium in three hypotensive patients. No satisfactory images were obtained by transthoracic imaging, which is often difficult in ventilated patients after cardiac surgery. Transoesophageal echocardiography, however, provided rapid diagnostic information and permitted prompt surgical intervention.
Images
PMCID: PMC1024682  PMID: 2054248
25.  Hypnotherapy and the GP. 
PMCID: PMC1335293  PMID: 2007244

Results 1-25 (44)