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J Deinum

Publications and source records attributed to J Deinum.

At least 19 recordsLinked to original sources
PubMed2006

Does masked hypertension exist in healthy volunteers and apparently well-controlled hypertensive patients?

BACKGROUND: Home blood pressure (HB P) measurement is considered to reflect BP during the day better than office BP (OB P). But in some patients HB P is higher than OB P. This is called masked hypertension (MH). OBJECTIVE: To examine whether MH occurs in healthy volunteers and apparently well-controlled hypertensives. METHODS: 57 treated hypertensive patients and 31 healthy volunteers (27/22 men) participated. Mean age (+/- SD ) was 61 +/- 13 and 29 +/- 13 years, respectively. Patients were instructed to measure their BP twice daily for three days (3 readings each) with the Omron 705 CP device after at least 10 minutes rest in a comfortable sitting position. In the outpatient department, OB P was measured four times, in duplicate, every ten minutes by the physician using the same device and under similar conditions. RESULTS: Mean HB P of the treated hypertensive group was 146/84 +/- 18/10 mmHg, significantly higher than OB P 136/79 +/- 19/10 (p.

Adult↗
PubMed2004

[From gene to disease; dopamine-beta-hydroxylase deficiency and orthostatic hypotension].

The DBH gene encodes dopamine-beta-hydroxylase (DbetaH), the enzyme that catalyses the formation of norepinephrine from dopamine. Inactivation of this enzyme due to a mutation of the DBH gene causes a selective (nor)-adrenergic failure of the sympathetic nervous system. This manifests as a severe orthostatic syndrome in which sweating and a normal parasympathetic function are preserved. Several mutations of the DBH gene that cause this very rare syndrome have now been identified. Diagnosis is made on the basis of clinical features and the finding of increased plasma dopamine in the near-absence of norepinephrine. A sole finding of absent plasma DbetaH is insufficient, since about 4% of the population have absent DbetaH. This trait cosegregates with a polymorphism in the promoter region of the DBH gene and is not associated with sympathetic failure. The orthostatic syndrome of DbetaH deficiency can be treated with the non-natural amino acid L-dihydroxyphenylserine, which is decarboxylated to norepinephrine by the ubiquitous aromatic-L-amino acid decarboxylase.

Dopamine↗
PubMed2004

Which patients with hypertension and atherosclerotic renal artery stenosis benefit from immediate intervention?

The objective was to identify subgroups of patients with hypertension and atherosclerotic renal artery stenosis who may benefit from immediate intervention. In the DRASTIC study, patients with hypertension, significant atherosclerotic renal artery stenosis, and a normal or mildly impaired renal function were randomized between immediate balloon angioplasty (PTRA; n=56) and drug therapy followed by angioplasty after 3 months, if needed (Med-PTRA; n=50). In this secondary analysis of the data, changes in the renal function and blood pressure after 1 year were studied by analysis of covariance in the following subgroups: patients with positive captopril-renin challenge test, abnormal captopril renogram, recently developed hypertension, bilateral stenosis, and severe stenosis. We found a benefit of immediate angioplasty only for patients with bilateral stenosis. Their creatinine clearance had decreased (mean+/-s.d.: -4.2+/-13.5 ml/min) in the Med-PTRA group, whereas it had improved substantially (+10.0+/-15.7 ml/min) in the PTRA group (P=0.02). For patients with unilateral stenosis, the change in creatinine clearance did not differ between PTRA and Med-PTRA (+4.3+/-15.5 and +1.3+/-12.5 ml/min, respectively). The patients with bilateral stenosis also seemed to benefit most from immediate intervention with regard to blood pressure control. None of the other subgroups had a clear benefit of immediate intervention regarding renal function or blood pressure control. In conclusion, intervention should not be postponed in patients with bilateral stenosis, even if renal function is normal. Other hypertensive patients with atherosclerotic renal artery disease could initially well be treated by aggressive multidrug therapy alone unless hypertension persists or renal function deteriorates.

Aged↗
PubMed2004

Congenital dopamine-beta-hydroxylase deficiency in humans.

Dopamine-beta-hydroxylase (DbetaH) deficiency is a rare autosomal dominant disorder. Due to the absence of DbetaH, there is a blocked conversion of dopamine into norepinephrine. The biochemical hallmark of this syndrome consists of a complete absence of plasma norepinephrine and epinephrine levels in conjunction with an increased plasma dopamine level. Several mutations in the gene that encodes for DbetaH have been described. Up to now, worldwide, 12 patients have been reported. The most important clinical feature is a severe orthostatic hypotension. In addition, several other clinical features like blepharoptosis, hyperflexible joints, high palate, sluggish deep tendon reflexes, and a mild normocytic anemia have been described. The only effective treatment of DbetaH deficiency is L-threo-3,4-dihydroxyphenylserine (DOPS). DOPS is converted directly into norepinephrine. Treatment with DOPS results in a sustained relief of orthostatic symptoms.

Dopamine beta-Hydroxylase↗
PubMed2003

[Primary hyperaldosteronism].

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.

Adenoma↗
PubMed2003

Polymorphism in the promoter region of the insulin-like growth factor I gene is related to carotid intima-media thickness and aortic pulse wave velocity in subjects with hypertension.

BACKGROUND AND PURPOSE: Low circulating levels of insulin-like growth factor I (IGF-I) have been associated with an increased risk for atherosclerosis. Absence of the 192-bp (wild-type) allele in the promoter region of the IGF-I gene has been associated with low circulating IGF-I levels. We examined the role of this polymorphism in relation to blood pressure and 2 early markers of atherosclerosis: carotid intima-media thickness (IMT) and aortic pulse wave velocity (PWV). METHODS: A total of 5132 subjects of the Rotterdam Study, aged 55 to 75 years, were included in this study. In 3769 subjects who did not use blood pressure-lowering medication, the association between the IGF-I polymorphism and blood pressure was examined. In the total population, and in 3484 normotensive subjects, 1648 hypertensive and 462 untreated hypertensive subjects, the association between this polymorphism and IMT and PWV was examined. RESULTS: Mean systolic and diastolic blood pressure did not differ between genotypes. In hypertensive subjects IMT was significantly increased in noncarriers of the 192-bp allele (0.83 mm) compared with heterozygous or homozygous carriers (0.80 mm) (P=0.04). PWV was also significantly higher in hypertensive subjects who were noncarriers of the 192-bp allele (14.3 m/s) compared with heterozygous (14.1 m/s) or homozygous carriers (13.7 m/s) (P=0.02). Findings were more pronounced in hypertensive subjects without medication use. In normotensive subjects, no association between this polymorphism, IMT, and PWV was observed. CONCLUSIONS: Our study suggests that hypertensive subjects who have low IGF-I levels because of a genetic polymorphism in the IGF-I gene are at increased risk of developing atherosclerosis.

Aged↗
PubMed2003

[Increased serum activity of angiotensin-converting enzyme (ACE): indication of sarcoidosis? A 'Bayesian' approach].

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.

Adult↗
PubMed2003

[Familial hyperactivity of angiotensin-converting enzyme (ACE)].

An extremely high level of serum angiotensin-converting enzyme (ACE) activity was found in eight individuals, women aged 31, 60, 42 and 67 years, and men aged 50, 47, 23 and 50 years. They had consulted a specialist due to a wide range of non-specific complaints or abnormalities (fatigue, dyspnoea, arthralgia, kidney stones with high urinary calcium, neurological symptoms and an elevated blood alkaline phosphatase activity level). As each of these complaints could be a symptom of sarcoidosis, the ACE activity was measured. However, sarcoidosis was not diagnosed in any of these patients. A subsequent analysis revealed that all eight individuals had family members with a similar elevation of ACE. Therefore, the increase in ACE activity was familial. Patients with this disorder have serum ACE levels of between 3 and 7 times the upper limit of normal, whereas in the case of sarcoidosis, serum ACE levels rarely exceed three times this limit. Familial ACE hyperactivity is not accompanied by clinical symptoms. It is caused by a point mutation in the ACE gene, which results in the cell-bound ACE being more readily loosened from the cell surface into the circulatory system.

Adult↗
PubMed2003

Acute pancreatitis after a course of clarithromycin.

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.

Acute Disease↗
PubMed2002

Shrinkage of the distal renal artery 1 year after stent placement as evidenced with serial intravascular ultrasound.

The objective of this study was to determine the quantitative intravascular ultrasound (IVUS) and angiographic changes that occur during 1 year follow-up after renal artery stent placement, given that restenosis continues to be a limitation of renal artery stent placement. 38 consecutive patients with symptomatic renal artery stenosis treated with Palmaz stent placement were studied prospectively. IVUS and angiography were performed at the time of stent placement and at 1 year follow-up. At follow-up, angiographic restenosis was seen in 14% of patients. The lumen area in the stent, seen with IVUS, was significantly decreased from 24+/-5.6 mm(2) to 17+/-5.6 mm(2) (p<0.001) solely due to plaque accumulation. The distal main renal artery showed a significant decrease in lumen area owing to a significant vessel area decrease from 39+/-14.0 mm(2) to 29+/-9.3 mm(2) (p<0.001) without plaque accumulation. Angiographic analysis confirmed this reduction in luminal diameter and showed that the distal renal artery diameter at follow-up was significantly smaller than before stent placement (86+/-23.0% vs 104+/-23.9% of the contralateral renal artery diameter; p=0.003). Besides plaque accumulation in the stent, unexplained shrinkage of the distal main renal artery was evidenced with IVUS and angiography 1 year following stent placement.

Aged↗
PubMed2001

Effect of different types of thrombin inhibitors on thrombin/thrombomodulin modulated activation of protein C in vitro.

The objectives of this study were to investigate whether the affinity of thrombin for small-molecule, active site-directed thrombin inhibitors and substrates is affected by the presence of thrombomodulin (TM), and to what extent thrombin inhibitors inhibit TM-bound thrombin. Inhibition of human alpha-thrombin was studied in the presence and absence of solubilised rabbit lung TM in a buffer containing CaCl(2). TM inhibited thrombin-induced proteolysis of human fibrinogen with a dissociation constant (K(D)) of 4 nmol/l. With at least 16-fold molar excess of TM over thrombin the affinity of thrombin both for the small thrombin substrates (S-2366 and S-2238) and the reversible, active site-directed thrombin inhibitors (inogatran and melagatran) increased twofold. In contrast, the ability of hirudin to inhibit thrombin was reduced by TM, since hirudin competes with TM in binding to thrombin. The effect of thrombin inhibitors on protein C activation by thrombin bound to human kidney cells transfected with cDNA for human TM was also studied. The mean binding capacity of the transfected cells was approximately 320,000 quantified by flow cytometry with antibodies against TM. Hirudin, inogatran and melagatran inhibited the activation of protein C by thrombin complexed with cell-bound TM in a dose-dependent manner, with mean IC(50) values+/-S.D. of 4.4+/-0.8, 20.0+/-1.1 and 6.4+/-0.2 nmol/l, respectively. Antithrombin inhibited protein C activation with an IC(50) value of 290+/-10 nmol/l, which was enhanced fourfold (IC(50) 60 nmol/l) by the addition of heparin 0.5 U/ml. Heparin alone, up to a concentration of 1 U/ml, had no effect on the activation of protein C. Small direct thrombin inhibitors thus inhibited both free and TM-bound thrombin and therefore also inhibited the activation of protein C. Whether this will influence their clinical efficacy or safety versus heparin and warfarin, which also inhibit protein activation, respectively, lowers the concentration of protein C, remains to be studied in clinical trials.

Antithrombins↗
PubMed2001

Angiotensin II type 2 receptors and cardiac hypertrophy in women with hypertrophic cardiomyopathy.

The development of left ventricular hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. Angiotensin II mediates both trophic and antitrophic effects, via angiotensin II type 1 (AT(1)-R) and angiotensin II type 2 (AT(2)-R) receptors, respectively. Here we investigated the effect of the AT(2)-R gene A/C(3123) polymorphism, located in the 3' untranslated region of exon 3, on left ventricular mass index (LVMI) in 103 genetically independent subjects with HCM (age, 12 to 81 years). LVMI and interventricular septum thickness were determined by 2D echocardiography. Extent of hypertrophy was quantified by a point score (Wigle score). Plasma prorenin, renin, and ACE were determined by immunoradiometric or fluorometric assays, and genotyping was performed by polymerase chain reaction. In men, no associations between AT(2)-R genotype and any of the measured parameters were observed, whereas in women, LVMI decreased with the number of C alleles (211+/-19, 201+/-18, and 152+/-10 g/m(2) in women with the AA, AC, and CC genotype, respectively; P=0.015). Similar C allele-related decreases in women were observed for interventricular septum thickness (P=0.13), Wigle score (P=0.05), plasma renin (P=0.03), and plasma prorenin (P=0.26). Multiple regression analysis revealed that the AT(2)-R C allele-related effect on LVMI (beta=-30.7+/-11.1, P=0.010) occurred independently of plasma renin, the AT(1)-R gene A/C(1166) polymorphism, or the ACE gene I/D polymorphism. In conclusion, AT(2)-Rs modulate cardiac hypertrophy in women with HCM, independently of the circulating renin-angiotensin system. These data support the contention that AT(2)-Rs mediate antitrophic effects in humans.

Adult↗
PubMed2001

Point mutation in the stalk of angiotensin-converting enzyme causes a dramatic increase in serum angiotensin-converting enzyme but no cardiovascular disease.

BACKGROUND: Angiotensin-converting enzyme (ACE) metabolizes many small peptides and plays a key role in blood pressure regulation. Elevated serum ACE is claimed to be associated with an increased risk for cardiovascular disease. Previously, two families with dramatically increased serum ACE were described, but no systematic survey of affected individuals was performed, and the molecular background of this trait is unknown. METHODS AND RESULTS: Eight families were identified with autosomal dominant inheritance of a dramatic (5-fold) increase of serum ACE activity. Strikingly, no clinical abnormalities were apparent in the affected subjects. Isolated blood cells were used for genetic and biochemical analysis. The level of ACE expression on the blood leukocytes and dendritic cells and total cell-associated ACE of the affected individuals was similar to that in nonaffected relatives; however membrane-bound mutant ACE was much more efficiently clipped from the cell surface compared with its wild-type counterpart. A point mutation causing Pro1199Leu in the stalk region of the ACE molecule cosegregates with the increase in serum ACE (LOD score, 6.63). CONCLUSIONS: A point mutation in the stalk region of the ACE protein causes increased shedding, leading to increased serum ACE, whereas cell-bound ACE is unaltered, and affected individuals exhibit no clinical abnormalities. These findings qualify the importance of serum ACE and establish a new determinant of ACE solubilization.

Adult↗
PubMed2001

[Clinical thinking and decision making in practice. A young women with muscle cramps].

A 23-year-old woman with a history of episodic stiffening of the limbs since her early adolescence, reported attacks of muscle contraction accompanied by feelings of panic but without loss of consciousness. Epileptic seizures, e.g. progressive myoclonic epilepsy, metabolic encephalopathy, dystonia and tetany were suggested. During the examination, muscle contraction could be provoked whilst measuring the blood pressure. Tetany based on primary hypoparathyroidism was diagnosed from the medical history as well as the neurological examination. This was confirmed by laboratory tests. She was successfully treated with calcium and I-alpha-(OH)2 vitamin D3.

Adult↗
PubMed2001

A regulatory hydrophobic area in the flexible joint region of plasminogen activator inhibitor-1, defined with fluorescent activity-neutralizing ligands. Ligand-induced serpin polymerization.

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.

Amino Acid Sequence↗
PubMed2001

Resistance to antihypertensive medication as predictor of renal artery stenosis: comparison of two drug regimens.

BACKGROUND: Renal artery stenosis is among the most common curable causes of hypertension. The definitive diagnosis is made by renal angiography, an invasive and costly procedure. The prevalence of renal artery stenosis is less than 1% in non-selected hypertensive patients but is higher when hypertension is resistant to drugs. OBJECTIVE: To study the usefulness of standardised two-drug regimens for identifying drug-resistant hypertension as a predictor of renal artery stenosis. DESIGN AND SETTING: Prospective cohort study carried out in 26 hospitals in The Netherlands. PATIENTS: Patients had been referred for analysis of possible secondary hypertension or because hypertension was difficult to treat. Patients < or =40 years of age were assigned to either amlodipine 10 mg or enalapril 20 mg, and patients >40 years to either amlodipine 10 mg combined with atenolol 50 mg or to enalapril 20 mg combined with hydrochlorothiazide 25 mg. Renal angiography was performed: (1) if hypertension was drug-resistant, ie if diastolic pressure remained > or =95 mm Hg at three visits 1-3 weeks apart or an extra drug was required, and/or (2) if serum creatinine rose by > or =20 micromol/L (> or =0.23 mg/dL) during ACE inhibitor treatment. RESULTS: Of the 1106 patients with complete follow-up, 1022 had been assigned to either the amlodipine- or enalapril-based regimens, 772 by randomisation. Drug-resistant hypertension, as defined above, was identified in 41% of the patients, and 20% of these had renal artery stenosis. Renal function impairment was observed in 8% of the patients on ACE inhibitor, and this was associated with a 46% prevalence of renal artery stenosis. In the randomised patients, the prevalence of renal artery stenosis did not differ between the amlodipine- and enalapril-based regimens. CONCLUSIONS: In the diagnostic work-up for renovascular hypertension the use of standardised medication regimens of maximally two drugs, to identify patients with drug-resistant hypertension, is a rational first step to increase the a priori chance of renal artery stenosis. Amlodipine- or enalapril-based regimens are equally effective for this purpose.

Adolescent↗