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Item does not contain fulltext Two patients, a man aged 23 and a woman aged 42 years, complained of fatigue and arthralgia respectively. A particularly high serum activity of angiotensin-converting enzyme (ACE) was established during the diagnostic work-up, although sarcoidosis was considered to be unlikely. This led to a series of diagnostic procedures, some invasive, to confirm the diagnosis of sarcoidosis. The diagnosis was not made in either of these patients. The fatigue appeared to be self-limiting and the arthralgia was due to arthrosis. Eventually it was discovered that these patients had a familial elevation of serum ACE activity. The elevation of ACE levels has limited specificity for sarcoidosis (85%) and is therefore of no value in the diagnostic workup, if the a priori probability for sarcoidosis is low.

Primary hyperaldosteronism (PHA), autonomic secretion of aldosterone by the adrenal gland, is rare. PHA usually results in therapy-resistant hypertension and is often but not always accompanied by hypokalaemia. Common causes of PHA are an aldosterone-producing adenoma, idiopathic aldosterone hypersecretion, unilateral hyperplasia or a genetic variant: glucocorticoid-remediable aldosteronism (GRA). The diagnosis should be phased and first of all requires a biochemical confirmation of the presence of PHA. In PHA patients, plasma renin is invariably suppressed. Blood should be collected under standardised conditions while the patient is not using beta-blockers or centrally-acting antihypertensive medication. Patients with a suppressed plasma renin and an elevated plasma aldosterone concentration have PHA. In patients with a suppressed plasma renin and a high-normal plasma aldosterone concentration a confirming test should be performed in which PHA is diagnosed if aldosterone is not suppressed following volume expansion with sodium chloride. The cause of PHA is determined by means of a CT scan or MRI of the adrenal glands to find a unilateral adenoma. If the CT scan or MRI is normal, adrenal vein aldosterone sampling may be considered as a next step in order to demonstrate lateralisation of aldosterone production. The hypertension and hypokalaemia of all forms of PHA respond well to spironolactone therapy. In the case of a unilateral adenoma or unilateral hyperplasia, adrenalectomy is the treatment of choice. For GRA, dexamethasone in doses that reduce the corticotropin (ACTH) level is indicated.

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Item does not contain fulltext Recently, the VA NEPHRON-D study was stopped early due to insignificant effects and increased adverse events. This was the last in a series of trials on the value of dual versus single blockade of the renin-angiotensin-aldosterone system in patients at risk for renal or cardiovascular complications. From these studies, the picture has emerged that dual blockade is hardly effective and increases the risk of hyperkalaemia and renal failure. Background use of beta blockers - little recognised indirect renin inhibitors - may play a role in the detrimental effects of dual blockade. Aldosterone antagonists in combination with one of the RAAS inhibitors may confer some benefit, but have not been studied sufficiently. For now, combining ACE inhibitors, angiotensin receptor blockers and aliskiren is to be discouraged.

We have characterized the neutralization of the inhibitory activity of the serpin plasminogen activator inhibitor-1 (PAI-1) by a number of structurally distinct organochemicals, including compounds with environment-sensitive spectroscopic properties. In contrast to latent and reactive center-cleaved PAI-1 and PAI-1 in complex with urokinase-type plasminogen activator (uPA), active PAI-1 strongly increased the fluorescence of the PAI-1-neutralizing compounds 1-anilinonaphthalene-8-sulfonic acid and 4,4'-dianilino-1,1'-bisnaphthyl-5,5'-disulfonic acid. The fluorescence increase could be competed by all tested nonfluorescent neutralizers, indicating that all neutralizers bind to a common hydrophobic area preferentially accessible in active PAI-1. Activity neutralization proceeded through two consecutive steps as follows: first step is conversion to forms displaying substrate behavior toward uPA, and second step is to forms inert to uPA. With some neutralizers, the second step was associated with PAI-1 polymerization. Vitronectin reduced the susceptibility to the neutralizers. Changes in sensitivity to activity neutralization by point mutations were compatible with the various neutralizers having overlapping, but not identical, binding sites in the region around alpha-helices D and E and beta-strand 1A, known to act as a flexible joint when beta-sheet A opens and the reactive center loop inserts as beta-strand 4A during reaction with target proteinases. The defined binding area may be a target for development of compounds for neutralizing PAI-1 in cancer and cardiovascular diseases. Udgivelsesdato: 2001-Apr-20

Item does not contain fulltext In a reasonably large proportion of patients who take antihypertensive drugs (10-30%), hypertension appears to be therapy resistant; even the use of three antihypertensives does not lower the blood pressure sufficiently. The average nocturnal blood pressure is a better predictor of cardiovascular events than blood pressure measured during the day. Antihypertensives have a stronger effect on nocturnal blood pressure when taken in the evening rather than in the morning. The exact mechanism of this has not yet been unravelled, but randomised, non-blinded studies suggest that this so-called chronotherapy does indeed lower cardiovascular risk in certain groups. The authors regard this as a promising strategy for patients with therapy-resistant hypertension in whom a nocturnal blood pressure dip does not occur.

Item does not contain fulltext We present a case of acute pancreatitis after a course of clarithromycin. An 84-year-old woman died of suspected pneumonia and cardiac failure. Autopsy surprisingly revealed acute pancreatitis. Except for the use of clarithromycin no other cause for her acute pancreatitis was obvious. Pancreatitis induced by clarithromycin has been reported twice in the English literature so far. There are, however, a few reports on acute pancreatitis associated with other macrolide antibiotics, such as erythromycin and roxithromycin.