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Biomedical subjects

C D Stehouwer

Publications and source records attributed to C D Stehouwer.

At least 163 records · Page 9Linked to original sources

Folic acid treatment of hyperhomocysteinemia in dialysis patients.

We measured fasting total plasma homocysteine (Hcy) in 10 chronic hemodialysis (HD) and 10 chronic peritoneal dialysis (PD) patients. Mean (+/- SEM) Hcy was 55.7 +/- 10.1 and 50.5 +/- 14.3 mumol/l, respectively (normal range 6-19 mumol/l). Hemodialysis treatment lowered Hcy by about 30%. Daytime Hcy concentrations were stable in the PD patients. Six weeks of treatment with folic acid (FA) significantly lowered Hcy in HD and PD patients to 24.0 +/- 1.8 and 21.0 +/- 3.6 mumol/l, respectively. After withdrawal, Hcy rose slowly, in parallel with the gradually decreasing plasma FA concentrations, which were greatly elevated during treatment. Chronic treatment with FA of another group of patients showed a similar effect on Hcy. Preliminary results of oral methionine loading in chronic dialysis patients were compatible with delayed homocysteine metabolism via the transsulfuration pathway. Further studies on the optimal treatment of hyperhomocysteinemia in chronic dialysis patients are needed.

Adult↗

Hyperhomocysteinaemia; with reference to its neuroradiological aspects.

Severe or even mild hyperhomocysteinaemia can cause a wide range of neurological problems. In recent years its vascular complications, including cerebral stroke, in children and young adults have gained special interest, because hyperhomocysteinaemia is treatable and recurrence of vascular incidents may be preventable. Current knowledge about biochemical mechanisms leading to hyperhomocysteinaemia, the pathogenesis of vascular pathology and neurological disfunction, and the various patterns of cerebral damage are reviewed. The significance of MRI in diagnosis, follow-up and research on hyperhomocysteinaemia is discussed.

Adolescent↗

Hyperhomocysteinaemia: a role in the accelerated atherogenesis of chronic renal failure?

Moderate hyperhomocysteinaemia has recently been established as an independent risk factor for atherothrombotic disease. It might be caused by heterozygosity for cystathionine beta-synthase deficiency, an enzyme involved in the conversion of methionine to cysteine through the transsulphuration pathway or by inherited thermolability of the enzyme which remethylates homocysteine into methionine. In chronic renal failure (CRF) homocysteine levels are significantly elevated at a relatively early stage. The normal kidney possibly plays an important role in homocysteine catabolism, which cannot be performed in CRF. Alternatively, decreased extrarenal catabolism can contribute to the hyperhomocysteinaemia in this disease state. Treatment with folic acid, 5 mg daily, significantly lowers homocysteine levels in chronic renal patients.

Adult↗

Analysis of twenty-four-hour ambulatory blood pressure monitoring: what time period to assess blood pressures during waking and sleeping?

OBJECTIVE: To study whether two widely used methods of analysis of ambulatory blood pressure monitoring (ABPM), which calculate means for fixed periods, provide accurate estimates of blood pressure during the true waking and sleeping periods. DESIGN AND METHODS: Ninety-five ABPM recordings were retrospectively analysed. Mean systolic and diastolic blood pressures during waking and sleeping were calculated in three ways: the waking and sleeping period according to the diary of the patient (diary method); the waking period from 0700 to 2200 h and the sleeping period from 2200 to 0700 h (9 h); and the waking period form 1000 to 2300 h and the sleeping period from 0100 to 0700 h (6 h). RESULTS: Systolic and diastolic blood pressures during the waking period were not different among the three methods of analysis. Compared with the diary method, the 9 h sleeping period method overestimated systolic blood pressure during sleep by 3.74 mmHg [99% confidence interval (CI) 2.70-4.77] and diastolic blood pressure by 2.44 mmHg (99% CI 1.75-3.14). In contrast, there was no significant difference between the diary method and the 6 h sleeping period method. CONCLUSIONS: The 6 h sleeping period method gave accurate estimates of blood pressure during sleep. The use of the long (9 h) sleeping period method should be avoided in studies in which sleeping-waking differences will be part of the analysis.

Activity Cycles↗

Endothelial dysfunction precedes development of microalbuminuria in IDDM.

In patients with insulin-dependent diabetes mellitus (IDDM), microalbuminuria is a predictor of widespread severe microangiopathy and macroangiopathy. Patients with microalbuminuria show generalized dysfunction of the vascular endothelium, but it is unknown whether endothelial dysfunction precedes the development of microalbuminuria. We examined a cohort of 17 IDDM patients at baseline and on three occasions during a follow-up of (median) 64 months (range 51-89). All had normal (< 15 micrograms/min) urinary albumin excretion (UAE) at the first three examinations. At the fourth examination, 11 patients had normal UAE and 6 had microalbuminuria (median 25.7 micrograms/min [range 15.3-42.8]). Compared with patients with normal UAE, microalbuminuric patients had significantly higher plasma levels of von Willebrand factor (vWF), a marker of endothelial dysfunction, at the second (200% [168-274] vs. 131% [69-186]), third (208% [188-270] vs. 125% [82-190]), and fourth examinations (231% [202-269] vs. 132% [88-208], P < 0.0001), but not at baseline (128% [98-161] vs. 122% [87-210]). An increase in vWF preceded the occurrence of microalbuminuria by approximately 3 years. The groups did not differ with regard to age, diabetes duration, blood pressure, mean glycated hemoglobin and cholesterol, smoking habits, or extent of retinopathy. Endothelial dysfunction, as estimated by plasma vWF concentration, precedes and may predict the development of microalbuminuria in IDDM.

Adult↗

Vessel wall properties of large arteries in uncomplicated IDDM.

OBJECTIVE: Patients with insulin-dependent diabetes mellitus (IDDM) are at high risk for cardiovascular disease. Arterial distensibility and compliance are vessel wall properties of large arteries. Altered large artery wall properties can be an early feature of vascular dysfunction. This study investigates vessel wall properties in 30 patients with uncomplicated IDDM and 30 matched healthy control subjects. RESEARCH DESIGN AND METHODS: Vessel wall properties of the elastic common carotid (CCA) and the muscular femoral (FA) and brachial arteries (BA) were measured with a vessel wall movement detector system. Blood pressure and heart rate were recorded simultaneously with a semiautomated device. Aortic pulse wave velocity was estimated from the carotido-femoral transit time. RESULTS: Blood pressure (IDDM patients: 118 +/- 10/69 +/- 5 mmHg), pulse pressure (IDDM patients: 49 +/- 8 mmHg), and heart rate (IDDM patients: 65 +/- 9 beats/min) were similar in IDDM patients and control subjects. No statistically significant changes between IDDM patients and control subjects were found for diameter, distensibility, and compliance of the elastic CCA and the muscular BA. Distensibility (IDDM patients: 16.9 +/- 6.4 10(-3)/kPa; control subjects: 22.4 +/- 11.8 10(-3)/kPa) of the muscular FA was decreased in IDDM (P < 0.05). However, FA compliance (IDDM patients: 0.80 +/- 0.23 mm2/kPa; control subjects: 0.94 +/- 0.41 mm2/kPa) and FA diameter (IDDM patients: 7.87 +/- 1.10 mm; control subjects: 7.57 +/- 1.11 mm) did not differ statistically between IDDM patients and control subjects. Aortic pulse wave velocity was the same in IDDM patients and control subjects (IDDM patients: 5.1 +/- 0.6 m/s). No relation was found between vessel wall properties and duration of disease, actual glucose level, and HbA1c for all three arteries (CCA, BA, and FA). But the groups might have been too small to draw conclusions. CONCLUSIONS: The results of the present study show that in this group of patients with uncomplicated IDDM, vessel wall properties of elastic and muscular large arteries were not obviously reduced when compared with healthy control subjects. However, distensibility of the FA was lower in IDDM patients. Early atherosclerotic changes in IDDM frequently occur at this site. A difference related to the duration of diabetes could not be excluded.

Adolescent↗

Combined vitamin B6 plus folic acid therapy in young patients with arteriosclerosis and hyperhomocysteinemia.

PURPOSE: Hyperhomocysteinemia is associated with arteriosclerotic and thromboembolic events. The homocysteine-lowering effect of combined treatment with vitamin B6 plus folic acid has never been explored in a large group of patients with vascular disease. Therefore we studied the effects of at least 6 weeks treatment with these vitamins in 72 patients with cardiovascular disease and mild hyperhomocysteinemia (defined as an increase of the plasma homocysteine level after methionine loading greater than 97.5 percentile of age-matched control subjects but less than 200 mumol/L). METHODS: The existence of mild hyperhomocysteinemia was investigated in 309 consecutive patients under 50 years of age with peripheral arterial occlusive disease, cerebral arterial occlusive disease, or coronary artery occlusive disease. All patients with an abnormal loading test result were treated with vitamin B6, 250 mg daily, plus folic acid, 5 mg daily. After 6 weeks of treatment a second methionine loading test was performed to assess the homocysteine-lowering effect. RESULTS: Mild hyperhomocysteinemia was detected in 72 patients (23%), 33 (46%) of whom also had hyperhomocysteinemia when fasting. Treatment with vitamin B6 plus folic acid normalized the postload plasma homocysteine concentration in 66 of the 72 patients (92%), whereas fasting hyperhomocysteinemia was normalized in 30 of 33 (91%) patients. In six patients therapy failed to achieve normalization of the postload homocysteine levels. In three of these patients, the same treatment was continued for an additional 6 weeks, and in the remaining three patients betaine was added to the treatment regimen. After 6 weeks of additional treatment all six patients had normal postload plasma homocysteine concentrations. CONCLUSION: The prevalence of mild hyperhomocysteinemia in young patients with arterial occlusive disease is high. Simple and inexpensive therapy with vitamin B6 plus folic acid will normalize homocysteine metabolism, as assessed by the homocysteine plasma level after methionine loading, in virtually all these patients.

Adult↗

Plasma endothelin levels and vascular effects of intravenous L-arginine infusion in subjects with uncomplicated insulin-dependent diabetes mellitus.

1. Uncomplicated insulin-dependent diabetes mellitus is associated with generalized vasodilatation. This vasodilatation is believed to contribute to the development of microvascular complications. The endothelium plays an important role in the regulation of vascular tone. 2. To investigate the role of endothelial mediators, we measured plasma endothelin levels and studied the vascular effects of intravenous L-arginine (the precursor of NO) in 10 male type 1 diabetic patients and 10 non-diabetic subjects. 3. The baseline plasma endothelin level was significantly lower in the diabetic patients [mean 1.7 (SD 0.5) versus 2.1 (0.4) pmol/l; P < 0.05] than in the control subjects. 4. During L-arginine infusion, plasma cyclic GMP (the second messenger for NO) increased in the control subjects [from 5.1 (2.9) to 6.9 (2.9) nmol/l; P < 0.05 versus saline] and in the diabetic patients [from 4.6 (1.8) to 5.7 (2.2) nmol/l; P = 0.09]. L-Citrulline (a by-product of NO synthesis from L-arginine) increased in both groups. The responses to L-arginine were not significantly different between the control subjects and the diabetic patients. The plasma atrial natriuretic peptide level did not change in either group during infusion of L-arginine or of an equal volume of isotonic saline. 5. Blood pressure decreased slightly during L-arginine administration in both groups. In control subjects, the extracellular fluid volume in the lower leg increased during L-arginine infusion as compared with saline; in the diabetic patients both L-arginine and saline increased the extracellular fluid volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of sex hormones on plasma endothelin levels.

OBJECTIVE: To determine whether a sex-associated difference in endothelin levels exists and to assess whether this difference is mediated by sex hormones. DESIGN: Initial survey in healthy persons, followed by a nonrandomized intervention. SETTING: A university teaching hospital. PATIENTS: Twenty-three healthy men, 29 healthy women, 20 pregnant women, and 12 male-to-female and 13 female-to-male transsexual patients. MEASUREMENTS: Plasma levels of endothelin were first assessed in healthy men, healthy women, and pregnant women; subsequently, endothelin levels were determined in male-to-female and female-to-male transsexual patients both before and during cross-gender hormone treatment. This treatment involves administration of testosterone esters to women and of ethynylestradiol and cyproterone acetate to men. RESULTS: Endothelin levels were higher in men than in women (5.9 +/- 1.2 compared with 4.17 +/- 0.67 pg/mL; P < 0.01). Endothelin levels were lower in pregnant women than in age- and sex-matched nonpregnant controls (2.19 +/- 0.73 compared with 4.17 +/- 0.67 pg/mL; P < 0.01). In 12 male-to-female transsexuals treated with estradiol and the progestational agent cyproterone acetate, endothelin levels decreased from 8.1 +/- 3.0 to 5.1 +/- 2.0 pg/mL (P < 0.01). In 13 female-to-male transsexuals treated with testosterone, endothelin levels increased from 6.2 +/- 1.1 to 7.8 +/- 1.2 pg/mL (P < 0.01). CONCLUSION: Sex hormones may modulate plasma endothelin levels, with male hormones raising levels and female hormones lowering them. This finding may be important in explaining sex-associated differences in susceptibility to atherosclerotic cardiovascular disease.

Adolescent↗

Effect of cilazapril on glucose tolerance and lipid profile in hypertensive patients with non-insulin-dependent diabetes mellitus.

Hypertension frequently complicates diabetes mellitus and is associated with an increased incidence of cardiovascular and microvascular complications. Angiotensin-I converting enzyme (ACE) inhibitors are effective antihypertensive agents and it has been suggested that they may improve glucose tolerance. We performed a double-blind, randomized study comparing treatment for 8 weeks with cilazapril, a new ACE inhibitor, or placebo on metabolic variables in 22 hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients. At week 8 no significant changes in fasting plasma glucose, fasting plasma insulin, haemoglobin A1 and plasma lipids had occurred. The areas under the glucose [placebo (mean +/- SD): 10.7 +/- 3.27 and 10.6 +/- 2.53; cilazapril: 11.9 +/- 3.23 and 12.1 +/- 2.9 mmol/l per 180 min at 0 and 8 weeks, respectively] and insulin curve [placebo (median and range): 47.4 (31.4-165.1) and 65.3 (16.8-190.8); cilazapril: 51.1 (23.8-132.0) and 57.6 (29.0-150.1) mU/l per 180 min at 0 and 8 weeks, respectively] after a standardized oral liquid test meal were unaltered. A significant decrease in mean arterial blood pressure was observed after cilazapril (122 +/- 8.6 and 106 +/- 8.3 mmHg at 0 and 8 weeks, respectively), in contrast to placebo (122 +/- 6.7 and 120 +/- 6.9 mmHg at 0 and 8 weeks, respectively). In conclusion, cilazapril does not affect metabolic control in hypertensive NIDDM patients, whereas it effectively reduces blood pressure.

Blood Glucose↗

Giant-cell arteritis with normal erythrocyte sedimentation rate: case report and review of the literature.

A high Erythrocyte Sedimentation Rate (ESR) is often seen as a sine qua non for the diagnosis of giant-cell arteritis. The percentages of histopathologically proven giant-cell arteritis associated with a normal ESR, however, are variously reported as 5 to 30%. We describe a patient with histopathologically proven giant-cell arteritis and a normal ESR. A review of literature identified 34 cases of giant-cell arteritis who showed a normal ESR. Their clinical symptoms and signs are compared with the characteristics of patients with giant cell arteritis and an elevated ESR. No distinctive clinical features were found. A normal ESR cannot be used to exclude the diagnosis of giant-cell arteritis.

Adult↗

Clinical usefulness of measurement of urinary albumin excretion in diabetes mellitus.

Mortality in diabetes mellitus is related mainly to its renal and cardiovascular sequelae. Microalbuminuria identifies those at increased risk of both complications, possibly because microalbuminuria is a marker of generalised endothelial dysfunction. Screening for microalbuminuria is of proven benefit in insulin-dependent diabetes, as therapeutic strategies are available that are at least partially effective. Such benefits have not yet been demonstrated in non-insulin-dependent diabetes. Arguments are presented to suggest that microalbuminuria should be defined on the basis of three or more daytime or 24-h urine collections. This increases sensitivity compared to the use of overnight urine collections while specificity is maintained.

Albuminuria↗

[Henoch-Schönlein purpura following treatment with streptokinase].

This article presents the clinical history of a man aged 64 who developed Henoch-Schönlein purpura after administration of streptokinase for acute myocardial infarction. Because of the increasing use of streptokinase it is assumed that type III hypersensitivity reactions to streptokinase will be seen more frequently. The first symptoms may arise after discharge from the hospital, as symptom-free periods of 3 to 21 days have been reported.

Humans↗

Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus.

Raised urinary albumin excretion (UAE) is associated with an increased risk of cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM). We have examined the role of endothelial dysfunction as a possible explanation for this association in 94 NIDDM patients by investigating UAE, new cardiovascular events, and plasma concentration of von Willebrand factor (vWF), an indicator of endothelial dysfunction. At baseline, 66 patients had normal UAE (less than 15 micrograms/min), which remained normal in 33 (group 1) and increased in 33 (to median 31.5 micrograms/min, group 2). In 28 patients, baseline UAE was abnormal (67.1 micrograms/min, group 3). Follow-up ranged between 9 and 53 months. vWF did not change in group 1 (median 128% at baseline and 123% at follow-up), but increased in group 2 (from 116 to 219%, p less than 0.0001) and group 3 (from 157 to 207%, p = 0.0005). Baseline level of and change in vWF were strongly related to the development of microalbuminuria (R2 = 0.60, p less than 0.0001), but cardiovascular risk factors were not (R2 = 0.14). Raised baseline UAE was associated with an increased risk of new cardiovascular events only in patients with vWF concentrations above the median (relative risk 3.66, 95% CI 1.3-11.9) and not in patients with lower vWF (0.19, 0.01-1.33). In addition, the cardiovascular risk associated with increased UAE was modified by low compared with high concentrations of serum high density lipoprotein cholesterol (2.86 [1.03-8.48] vs 0.15 [0.01-1.43]). Dysfunction of vascular endothelium may be a link between albuminuria and atherosclerotic cardiovascular disease in NIDDM.

Adult↗

von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion.

High plasma levels of von Willebrand factor, an indicator of endothelial cell dysfunction, have been reported in both diabetic retinopathy and nephropathy. It is unclear, however, whether von Willebrand factor is related to diabetic retinopathy in the absence of diabetic nephropathy. The relationship between retinal status and plasma von Willebrand factor concentration was investigated in a cohort of 17 patients with Type 1 (insulin-dependent) diabetes mellitus who were followed-up for a median of 42 months. The patients were examined three times. They were selected for having had normal urinary albumin excretion and no evidence of retinopathy (on fundoscopy) at the first and second examination. They were then divided into two groups, according to absence (Group A; n = 9) or presence (Group B; n = 8) of retinopathy on fundoscopy or fluorescein angiography at the third examination. Urinary albumin excretion remained normal in all patients. Plasma von Willebrand factor levels were similar in both groups: (median) 128 vs 123%, 164 vs 132% and 159 vs 130% (first, second and third examination, respectively). Median changes in plasma von Willebrand factor were also similar: +7 vs +9% and +5 vs +1% (first-second and second-third examination). Patients in whom the plasma von Willebrand factor concentration increased had higher systolic blood pressure at the third examination (150 +/- 30 vs 130 +/- 12 mmHg, p = 0.02) when compared to those in whom plasma von Willebrand factor did not increase, but were of similar age and had similar diabetes duration, retinal status, diastolic blood pressure, glycated haemoglobin and serum cholesterol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Plasma endothelin levels are increased during septic shock.

OBJECTIVE: To study whether serially measured plasma concentrations of endothelin (a novel, potent, endogenous vasoconstrictor derived from endothelium and macrophages) relate to the pathophysiology and severity of human septic shock. DESIGN: Prospective analysis. SETTING: Medical ICU of a university hospital. PATIENTS: Six patients with septic shock, studied for 8 days after ICU admission. MEASUREMENTS AND MAIN RESULTS: The initial plasma endothelin concentration was increased (14.2 +/- 5.2 [SD] vs. normal 4.2 +/- 0.7 pg/mL, p less than .05) and correlated with the Acute Physiology and Chronic Health Evaluation II score (r2 = .79, p less than .05). For pooled data, endothelin levels correlated poorly with leukocyte counts (r2 = .13), mean arterial pressure (MAP) (r2 = .16), and administered doses of dopamine (r2 = .26). In multiple regression analyses, plasma endothelin concentrations were predicted by dopamine doses and not by MAP. Plasma endothelin concentrations predicted the decrease in creatinine clearance, independently from MAP. The pooled value for correlations between endothelin levels and creatinine clearance, during the course of disease in individual patients, was statistically significant (r2 = .31). CONCLUSIONS: During septic shock, the release or production of endothelin may increase as a consequence of endothelial injury by activated leukocytes and the infusion of catecholamines, and this mechanism may relate to renal vasoconstriction and to the severity of disease.

Analysis of Variance↗