William Withering's portrait.

The story of how William Withering's portrait painted in Birmingham in 1792 ended up in the Swedish Nationalmuseum 139 years later.

The serological diagnosis of staphylococcal infective endocarditis.

OBJECTIVES: Establishing the diagnosis of infective endocarditis (IE) can be difficult when blood cultures remain sterile or echocardiography is inconclusive. Staphylococcus aureus is a common aetiological microorganism in IE and is associated with severe valvular destruction and increased mortality. Early diagnosis using culture and antibiotic independent tests would be preferable to allow prompt antibiotic administration. We have developed and evaluated 2 serological assays for the rapid identification of a staphylococcal aetiology in infective endocarditis. The assays measure IgG against whole cells of S. aureus and IgG against lipid S, a novel extracellular antigen released by Gram-positive microorganisms. METHODS: Serum was collected from 130 patients with IE and 94 control patients. IgG against whole cells of S. aureus and against lipid S was measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Anti-lipid S IgG titres were higher in IE caused by Gram-positive microorganisms than in controls (p<0.0001) and higher in staphylococcal IE than in both controls and IE caused by other microorganisms (p=0.0003). Anti-whole cell staphylococcal IgG was significantly higher in serum from patients with staphylococcal IE than in IE caused by other microorganisms and control samples (p<0.0001). CONCLUSION: High anti-whole cell IgG titres are predictive of a staphylococcal aetiology in IE. Elevated serum anti-lipid S IgG titres are predictive of Gram-positive infection compared to controls, very high titres being associated with staphylococcal IE.

Heart and mind: (1) relationship between cardiovascular and psychiatric conditions.

The relationship of our emotions and psyche to heart disease is intriguing. In this article we have reviewed the evidence linking cardiovascular and neuropsychiatric disorders and the possible mechanisms and pathophysiology of this association. This review is derived from Medline searches (1966-2002) using the relevant search terms (psychiatric disease, cardiovascular disease, depression, anxiety, and pathophysiology). Finally, the possible role of using mood enhancing therapies (mainly antidepressants) and their safety in patients with cardiovascular disorders is briefly discussed. In a companion paper, the therapeutic aspects of these two conditions is highlighted.

Detection of bacterial DNA in cardiac vegetations by PCR after the completion of antimicrobial treatment for endocarditis.

PCR with broad-range primers for prokaryotic 16S rRNA genes was used to identify bacterial DNA in tissue from patients undergoing valve replacements following a previous episode of infective endocarditis (IE). Of eight valves investigated, bacterial DNA was detected in three from patients for whom IE had been treated by antibiotic therapy 5, 12 and 18 months previously. The demonstration of bacterial DNA within resected heart valves suggests either recurrence of infection, treatment failure or the persistence of bacterial debris within the cardiac vegetation. There may also be implications for routine use of PCR in the diagnosis of infection.

Use of diuretics in cardiovascular disease: (2) hypertension.

Hypertension is a common condition associated with increased mortality and multiple morbidities. Evidence based management of hypertension is known to improve both the short term and the long term outcomes in patients with this condition. There are several general measures and pharmacological agents that are known to treat hypertension adequately. Diuretics, in particular low dose thiazide and thiazide-like diuretics, are widely used in the treatment of hypertension. They have excellent outcome data and high safety and low side effects profiles. In this article, the physiology, pharmacological actions, side effects, and outcome data of the use of diuretics in hypertension are reviewed. In addition, the effective use of diuretics in the management of hypertension is discussed.

Use of diuretics in cardiovascular diseases: (1) heart failure.

Diuretics are used extensively in hospitals and in community medical practice for the management of cardiovascular diseases. They are used frequently as the first line treatment for mild to moderate hypertension and are an integral part of the management of symptomatic heart failure. Although diuretics have been used for several decades, there is still some ambiguity and confusion regarding the optimal way of using these common drugs. In this paper, the classes and action of diuretics are reviewed, and the various indications, optimal doses, and recommendations on the effective use of these agents are discussed.

Evaluation of PCR in the molecular diagnosis of endocarditis.

OBJECTIVE: Infective endocarditis (IE) is diagnosed by the Duke criteria, which can be inconclusive particularly when blood cultures are negative. This study investigated the application of polymerase chain reaction (PCR) to identify bacterial DNA in excised valvular tissue, and its role in establishing the diagnosis of IE. METHODS: Ninety-eight patients undergoing valve replacement surgery were studied. Twenty-eight patients were confirmed as definite for endocarditis by the Duke criteria; nine were considered as possible and 61 had no known or previous microbial infection of the endocardium. A broad-range PCR technique was used to amplify prokaryotic 16S rRNA genes present within homogenised heart valve tissue. Subsequent DNA sequencing of the PCR amplicon allowed identification of the infecting microorganism. RESULTS: PCR results demonstrated the presence of bacterial DNA in the heart valves obtained from 14 out of 20 (70%) definite IE patients with positive blood cultures preoperatively. The causative microorganism for one patient with definite culture negative endocarditis was identified by PCR. Two out of nine (22%) of the valves from possible endocarditis patients also had bacterial DNA present converting them into the definite criteria whereas in the valves of seven out of nine (78%) of these patients no bacterial DNA was detected. CONCLUSION: The application of PCR to the explanted valves in patients with possible or confirmed diagnosis can augment the Duke criteria thereby improving post-surgical antimicrobial therapeutic options.

The microbial diagnosis of infective endocarditis.

This review suggests an evidence-based algorithm for sequential testing in infective endocarditis. It discusses blood culture and the merits and drawbacks of serology in making the diagnosis. Newer techniques are briefly reviewed. The proposed algorithm will complement the Duke criteria in clinical practice.

Haemophilus paraphrophilus prosthetic valve endocarditis.

We report a case of prosthetic, aortic valve, infective endocarditis caused by Haemophilus paraphrophilus. There are no other cases described in the available literature where this microorganism has caused prosthetic valve endocarditis and no other case reported involving only the aortic valve.

Effects of angiotensin II (AT1) receptor blockade on cardiac vagal control in heart failure.

The objective of the present study was to determine the autonomic effects of angiotensin II (AT(1)) receptor blocker therapy in heart failure. In a randomized double-blind cross-over study, we compared the effects of candesartan and placebo on baroreflex sensitivity and on heart rate variability at rest, during stress and during 24 h monitoring. Acute effects were assessed 4 h after oral candesartan (8 mg) and chronic effects after 4 weeks of treatment (dose titrated to 16 mg daily). The study group comprised 21 patients with heart failure [mean (S.E.M.) ejection fraction 33% (1%)], in the absence of angiotensin-converting enzyme (ACE) inhibitor therapy. We found that acute candesartan was not different from placebo in its effects on blood pressure or mean RR interval. Chronic candesartan significantly reduced blood pressure [placebo, 137 (3)/82 (3) mmHg; candesartan, 121 (4)/75 (2) mmHg; P<0.001; values are mean (S.E.M.)], but had no effect on mean RR interval [placebo, 857 (25) ms; candesartan, 857 (21) ms]. Compared with placebo there were no significant effects of acute or chronic candesartan on heart rate variability in the time domain and no consistent effects in the frequency domain. Baroreflex sensitivity assessed by the phenylephrine bolus method was significantly increased after chronic candesartan [placebo, 3.5 (0.5) ms/mmHg; candesartan, 4.8 (0.7) ms/mmHg; P<0.05], although there were no changes in cross-spectral baroreflex sensitivity. Thus, in contrast with previous results with ACE inhibitors, angiotensin II receptor blockade in heart failure did not increase heart rate variability, and there was no consistent effect on baroreflex sensitivity.

Rapid serodiagnosis of gram-positive bacterial endocarditis.

OBJECTIVES: To characterize a serological test for diagnosing endocarditis caused by Gram-positive cocci. METHODS: We have developed an indirect enzyme-linked immunosorbent assay (ELISA) for the serological detection of Gram-positive infections. The test measures serum IgG directed towards lipid S, a recently identified exocellular glycolipid antigen which is related to lipoteichoic acid. We have previously shown the test to be of value in serodiagnosis of central venous catheter-associated sepsis and infection of orthopaedic prostheses caused by coagulase-negative staphylococci. We now describe the application of this test in endocarditis. RESULTS: Serum IgG levels to lipid S were significantly elevated in 34 patients with Gram-positive bacterial endocarditis confirmed as 'definite' by the Duke criteria as compared to 50 control patients. The test had a sensitivity of 88% and a specificity of 88%. CONCLUSIONS: The assay is independent of culture results or endocardial imaging, making it complementary to currently used investigations. It may therefore be possible to refine the current Duke criteria for diagnosing endocarditis. We describe an algorithm which incorporates lipid S serology into a positive diagnostic strategy.

Renal pathological findings in infective endocarditis.

BACKGROUND: Accounts of renal pathological findings in infective endocarditis are mostly based on studies from many years ago. We reviewed a group of patients with infective endocarditis in the light of modern concepts of renal pathology, including the largest reported series of renal biopsies in this condition. METHODS: Renal tissue was available for retrospective study from 62 patients with confirmed infective endocarditis out of 354 diagnosed with the disease between 1981 and 1998 inclusive. Twenty patients had a renal biopsy and 42 a necropsy. RESULTS: Common renal lesions noted were localized infarcts in 31%, noted only in necropsy material, and acute glomerulonephritis in 26%, noted in biopsy and necropsy material. The commonest type of glomerulonephritis was vasculitic, without deposition of immunoproteins in glomeruli. Of the renal infarcts over half were due to septic emboli, mostly in patients infected with Staphylococcus aureus. Acute interstitial nephritis was found in 10% but was more common in biopsy material and seemed attributable to antibiotics. Renal cortical necrosis found in 10% was apparent only at necropsy. There were various other findings in the kidney. CONCLUSIONS: The kidneys are commonly affected in infective endocarditis by a variety of complications of clinical significance. The commonest type of glomerulonephritis does not appear to be attributable to deposition of immune complexes. A renal biopsy may be helpful in the investigation of renal impairment in a patient with infective endocarditis.

Identification of a novel antigen from Staphylococcus epidermidis.

A genomic DNA library of Staphylococcus epidermidis NCTC 11047 was constructed, using the Lambda Zap Express cloning vector, and screened with serum collected from a patient with S. epidermidis endocarditis. Sequence analysis of a 30 kDa cloned protein, termed staphylococcal secretory antigen, SsaA, identified a novel protein not previously reported in S. epidermidis. SsaA showed strong homology with two other staphylococcal proteins: SceB from Staphylococcus carnosus and a staphyloxanthin biosynthesis protein from Staphylococcus aureus. Further investigation revealed SsaA to be a highly antigenic protein that was expressed in vivo and could be recovered from whole cells and from the culture supernatant. A combination of Western blot analysis and PCR screening identified SsaA or a homologue in 103/103 staphylococcal strains. SsaA-like genes were not detected in other Gram-positive bacteria of medical importance or a number of Gram-negative organisms. Elevated anti-SsaA IgG antibody levels were detected in sera of five patients with S. epidermidis endocarditis but not in patients with other S. epidermidis infections, endocarditis of other aetiologies or patients with no evidence of infection. The expression of SsaA during episodes of S. epidermidis endocarditis suggests a virulence role specific to the pathogenesis of this infectious disease.

The effects of acute and chronic dihydropyridine calcium antagonist therapy on baroreflex sensitivity: a re-analysis using the sequence method.

The objective of this study was to examine the effects of dihydropyridine calcium antagonist therapy on 24-h baroreflex sensitivity. Twenty-three patients with moderate essential hypertension were studied before and during acute (10 patients) and chronic (21 patients) treatment with a dihydropyridine calcium antagonist (nifedipine, nicardipine or felodipine) as monotherapy in a dose titrated to produce a fall in mean cuff pressure of at least 10%. Twenty-four hour unrestricted ambulatory intra-arterial blood pressure (IABP) and heart rate (R-R interval) were monitored. Baroreflex sensitivity (BRS) was assessed throughout the 24-h period by off-line computer analysis of spontaneous variations in IABP and R-R interval. During acute first dose treatment with a calcium antagonist there was a significant fall in blood pressure (BP), increase in heart rate and reduction in BRS. With chronic therapy (6-16 weeks) there was a continued reduction in mean BP of 11% (P < 0.001), but heart rate had returned to control levels and BRS was significantly increased over the 24 h by 14% (P < 0.01). The increase in BRS was evident during both the waking and sleeping periods, but the greatest increase was during sleep (awake 12% P = 0. 02, asleep 28% P = 0.003). In conclusion, although dihydropyridine calcium antagonists acutely cause a reflex tachycardia associated with a reduced BRS, there is no such effect with chronic therapy. BRS was significantly increased after chronic treatment, with exaggeration of the diurnal pattern. Journal of Human Hypertension (2000) 14, 189-194.