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Biomedical subjects

P Biemond

Publications and source records attributed to P Biemond.

16 recordsLinked to original sources
PubMed2004

Autonomic nervous function, arterial stiffness and blood pressure in patients with Type I diabetes mellitus and normal urinary albumin excretion.

Type I diabetic patients (DM-1) with an elevated urinary albumin excretion (UAE>30 mg/24 h) have a high cardiovascular risk. However, DM-1 patients with normal UAE have incipient abnormalities of the cardiovascular and nervous systems, such as elevations of blood pressures, increases in arterial stiffness and deterioration of autonomic nervous function. We studied the interrelationships of these abnormalities in normoalbuminuric DM-1 patients. In 76 patients, we performed two cardiovascular reflex tests (deep in- and expiration test (IE test) and lying-to-standing test (LS test)), and determined aortic pulse wave velocity (PWV), local arterial compliances of the common carotid, femoral and brachial arteries, and 24-h blood pressures. The DeltaRRmax value of the LS test was associated with aortic PWV (negatively) and the compliance coefficients of the carotid, femoral and brachial arteries. Per 100-ms increase in DeltaRRmax, pulse wave velocity decreased by 0.39 m/s, compliance coefficients of the carotid, femoral and brachial arteries increased by 0.06, 0.08 and 0.05 mm2/kPa, respectively. These associations were independent of age, 24-h mean arterial pressure and 24-h heart rate. Increases in arterial stiffness were associated with increases in 24-h systolic and pulse pressure (per 1 m/s increase in PWV, systolic and pulse pressure increased by 2.1 and 1.7 mmHg, respectively). In normoalbuminuric DM-1 patients, deterioration of autonomic nervous function is associated with an increase in arterial stiffness, which, in turn, was associated with, and may cause, increased systolic and pulse pressure. These findings suggest that preventive strategies targeting autonomic dysfunction may reduce cardiovascular morbidity in diabetes.

Adult↗
PubMed1999

The continuous 7-hour intravenous dexamethasone suppression test in the differential diagnosis of ACTH-dependent Cushing's syndrome.

OBJECTIVE: A recent report showing disappointingly low sensitivity and specificity for the oral high dose dexamethasone test in the differential diagnosis of Cushing's syndrome prompted us to re-evaluate the results obtained in our centre using the continuous 7-hour intravenous dexamethasone suppression test for this purpose. PATIENTS: 105 patients with ACTH-dependent Cushing's syndrome were included in this study; 78 with Cushing's disease, 8 with ectopic ACTH-secreting tumours and 19 were classified as 'of unknown aetiology'. RESULTS: In 74/78 (94.9%) of patients with Cushing's disease and in 3/8 (37.5%) patients with the ectopic ACTH syndrome, a plasma cortisol decrease > 190 nmol/l at 7 h as compared to baseline values was achieved in the continuous 7-hour intravenous dexamethasone suppression test. Using a plasma cortisol decrease > 190 nmol/l at 7 h as compared to baseline values as the cut-off value, the sensitivity and specificity of the continuous 7-hour intravenous dexamethasone suppression test for the diagnosis of Cushing's disease in patients with ACTH-dependent Cushing's syndrome were 94.9% and 62.5%, respectively. CONCLUSIONS: In patients with ACTH-dependent Cushing's syndrome with a plasma cortisol decrease > 190 nmol/l at 7 h in the continuous 7-hour intravenous dexamethasone suppression test, additional localizing investigations such as bilateral simultaneous inferior petrosal sinus sampling and/or pentetreotide scintigraphy should be performed when no clearly discernible pituitary adenoma is observed on MRI studies. Patients with ACTH-dependent Cushing's syndrome with a plasma cortisol decrease < 190 nmol/l at 7 h in the continuous 7-hour intravenous dexamethasone suppression test should also undergo bilateral simultaneous inferior petrosal sinus sampling and/or pentetreotide scintigraphy to demonstrate the presence of a nonpituitary source of ACTH overproduction.

ACTH Syndrome, Ectopic↗
PubMed1992

Cortisol receptor resistance: the variability of its clinical presentation and response to treatment.

Primary (partial) cortisol receptor resistance was previously reported in a total of 7 patients and 14 asymptomatic family members. Its occurrence is considered to be extremely rare. In the present study we report on 6 patients (2 males and 4 females) with the syndrome. The first male patient presented with mild hypertension. Hydrochlorothiazide therapy resulted in life-threatening hypokalemia. The second male patient had slight hypertension without hypokalemia. All four female patients presented between the age of 20-30 yr with acne, hirsutism, and irregular menstruations. Low dose dexamethasone therapy (1-1.5 mg/day) was of clinical benefit in these patients. All patients showed insufficient suppression of serum cortisol concentrations in the overnight 1-mg dexamethasone test. The diurnal rhythm of ACTH and cortisol was intact, albeit at an elevated level. There was a normal increase in ACTH, cortisol, and GH (except in one obese patient) in response to insulin-induced hypoglycemia, while cortisol production was elevated in three patients. Circulating adrenal androgen levels were increased in all patients. Glucocorticoid receptors were investigated in a whole cell dexamethasone binding assay in mononuclear leukocytes. In the first male patient, the number of receptors was very low, while the affinity was lower than that in controls. A lowered affinity to dexamethasone was found in one female patient, while a lowered number of receptors was found in three patients. In the second male patient, no abnormalities were found. As a bioassay for glucocorticoid action we also measured dexamethasone suppressibility of mitogen-stimulated incorporation of [3H]thymidine in mononuclear leukocytes. In the male patient with normal receptor status, dexamethasone suppressibility of [3H]thymidine incorporation was significantly lower than that in healthy controls with respect to both maximal suppression and IC50. Partial cortisol receptor resistance might be less rare than previously thought. In the six patients presented, at least three different forms can be recognized. Therapy with dexamethasone was successful in female patients with acne and hirsutism, as the secondary increase in the production of adrenal androgens was effectively controlled.

Acne Vulgaris↗
PubMed1991

Esophageal verrucous carcinoma: histologically a low-grade malignancy but clinically a fatal disease.

A 76-year-old woman had a verrucous carcinoma of the esophagus with a fistula of the left main bronchus. We discuss this case together with those of eleven other patients with verrucous carcinoma of the esophagus reported previously. Differentiation between this tumor and squamous cell papilloma is often difficult. The central cores of fibrous tissue in verrucous carcinoma are heavily infiltrated with inflammatory cells, which accounts for the stenosis often found. The mortality in verrucous carcinoma of the esophagus is 67% even though histologically it is a low-grade malignancy.

Adult↗
PubMed1990

Continuous dexamethasone infusion for seven hours in patients with the Cushing syndrome. A superior differential diagnostic test.

STUDY OBJECTIVE: To determine the usefulness of the continuous intravenous dexamethasone suppression test in the differential diagnosis of patients with the Cushing syndrome. DESIGN: Comparison of the results of this test with those of other tests in the study population and with data from the literature. SETTING: Referral-based endocrine division in a university hospital. PATIENTS: One hundred and twenty-one patients with the Cushing syndrome were evaluated: corticotropin (ACTH)-secreting pituitary tumors, 90 cases; adrenal adenoma, 13; adrenal carcinoma, 9; ectopic ACTH-secreting tumors, 6; corticotropin-releasing-hormone (CRH)-secreting tumors, 2; and autonomous bilateral micronodular adrenal hyperplasia, 1. The continuous intravenous dexamethasone suppression test was done in 101 patients. MEASUREMENTS AND MAIN RESULTS: Dexamethasone (1 mg/h) was administered intravenously for 7 hours. A cortisol decrease of at least 190 nmol/L was defined as a positive response. In identification of patients with ACTH-secreting pituitary adenomas, this test had a sensitivity of 100% (95% CI, 95% to 100%), a specificity of 90% (CI, 70% to 99%), and a diagnostic accuracy of 98% (CI, 93% to 100%). Only two patients had false test results. They both had CRH-secreting tumors. Cortisol secretion was also shown to be sensitive for feedback control in other tests, however. CONCLUSION: The continuous intravenous dexamethasone suppression test has better diagnostic accuracy than other tests that are currently used in the differential diagnosis of the Cushing syndrome, and this test is very convenient. The only false test results were found in patients with CRH-secreting tumors.

Adenoma↗
PubMed1990

Diminished superoxide production of synovial fluid neutrophils in patients with rheumatoid arthritis following piroxicam treatment.

Superoxide production by polymorphonuclear leukocytes (PMNs) and macrophages was inhibited by piroxicam and other non-steroidal anti-inflammatory drugs both in vitro and in vivo. Hitherto, data have only been available on blood PMNs and macrophages. In order to investigate the situation in the joint, PMNs were isolated from synovial fluid before and after 24 h of piroxicam treatment in patients with rheumatoid arthritis. Isolated PMNs were stimulated with PMA and serum-treated zymosan. The capacity of synovial fluid PMNs to produce superoxide decreased by 30% after piroxicam treatment. A similar decrease was found for blood PMNs. No difference in superoxide production was found between blood PMNs and synovial fluid PMNs which were obtained simultaneously. From the fact that the piroxicam concentration in synovial fluid was 40% of the serum value, it can be concluded that piroxicam probably became bound to PMNs before they entered the joint cavity. These results indicate that at the site of the inflammation the superoxide production by PMNs is inhibited by piroxicam treatment. The inhibition of superoxide production is probably important in the effect of piroxicam and other non-steroidal anti-inflammatory drugs in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1989

Familial and iatrogenic cortisol receptor resistance.

A family is described in which the father, a daughter, and two sons had cortisol receptor resistance. Hirsutism, skull baldness, and menstrual irregularities existed only in the female patient, while all three males were asymptomatic. The syndrome was transmitted via a dominant autosomal trait. A lowered dexamethasone affinity and a lowered number of glucocorticoid receptors were detected on the peripheral mononuclear leukocytes of the female patient. Chronic administration of the glucocorticoid receptor-blocking agent mifepristone (RU 38486) to normal individuals resulted in resetting of the hypothalamo-pituitary-adrenal axis at a higher level, while the diurnal rhythm of cortisol and the responsiveness to corticotropin releasing factor remained present. In four postmenopausal women this resulted in a considerable increase in circulating androstenedione levels (and eventually of estradiol levels). This iatrogenic RU 38486-induced biochemical syndrome is similar and difficult to differentiate from familial cortisol receptor resistance. Among a group of patients with so-called "idiopathic hirsutism," four patients were recognized with elevated androstenedione and (slightly) elevated cortisol levels which showed abnormalities in the affinity and/or number of glucocorticoid receptors on their peripheral mononuclear leukocytes. Therefore it is hypothesized that the syndrome of (partial) glucocorticoid receptor resistance is far more common than currently thought, especially among the group of patients with so-called "idiopathic hirsutism."

Adrenocorticotropic Hormone↗
PubMed1988

Superoxide dependent iron release from ferritin in inflammatory diseases.

Convincing evidence is presented that oxygen free radicals are involved in the pathogenesis of rheumatoid arthritis (RA). Superoxide is produced by polymorphonuclear leucocytes (PMN) in synovial fluid and by macrophages in the synovial membrane. Tissue damage typical for free radical attack is detected in RA. No absolute deficiency of protective factors is found in RA compared to controls, but the available protection is insufficient to cope with all radicals formed. The toxicity of superoxide is increased by iron. It is doubtful whether a low molecular weight iron pool is present. Superoxide is able to release iron from ferritin, providing a suitable source of iron, for the formation of hydroxyl radicals. This new pathogenetic mechanism stimulates to the application of iron chelators in the treatment of RA. Preliminary results with desferrioxamine were disappointing because of serious side-effects. Hopefully in the future intra-articular injection of iron chelators with better pharmacodynamics will be possible. The interaction of free radicals and ferritin is probably also involved in the pathogenesis of other inflammatory diseases such as systemic lupus erythematosus, hepatitis, and haemochromatosus.

Animals↗
PubMed1987

Lipid peroxidation and myocardial ischaemic damage: cause or consequence?

Compelling evidence has been accumulated which indicates that myocardial tissue damage occurring during reperfusion after an ischaemic period may partly be due to the formation of oxygen free radicals and subsequent peroxidative processes. It has been well established that the actual toxicity of free radicals is dependent on the presence of free iron in the heart tissue. Based upon the hypothesis of McCord et al., proposing xanthine oxidase mediated formation of superoxide (O2-.) during the conversion of ATP-breakdown product(s) (hypo)xanthine to urate, we studied whether xanthine oxidase was able to mobilize free iron from the intra- and extracellular iron-binding proteins, ferritin and transferrin. It appeared that there was an O2-.-dependent and O2-.-independent mechanism by which xanthine oxidase could mobilize iron from ferritin while no iron mobilization from transferrin was detectable. The capacity of xanthine oxidase to mobilize iron from ferritin by an O2-.-independent mechanism implies that already during the anoxic/ischaemic period, iron may become available in the tissue which, upon the re-entrance of O2, catalyzes the formation of the very reactive OH radicals. The interaction between endothelial cells and cardiocytes in free radical homeostasis is discussed with the emphasis on the tissue localization of xanthine oxidase. The latter is located in endothelial cells implying an interaction between xanthine oxidase-induced endothelial cells initiated lipid peroxidation and the actual overall myocardial tissue damage.

Animals↗
PubMed1986

Superoxide-dependent and -independent mechanisms of iron mobilization from ferritin by xanthine oxidase. Implications for oxygen-free-radical-induced tissue destruction during ischaemia and inflammation.

Xanthine oxidase is able to mobilize iron from ferritin. This mobilization can be blocked by 70% by superoxide dismutase, indicating that part of its action is mediated by superoxide (O2-). Uric acid induced the release of ferritin iron at concentrations normally found in serum. The O2(-)-independent mobilization of ferritin iron by xanthine oxidase cannot be attributed to uric acid, because uricase did not influence the O2(-)-independent part and acetaldehyde, a substrate for xanthine oxidase, also revealed an O2(-)-independent part, although no uric acid was produced. Presumably the amount of uric acid produced by xanthine oxidase and xanthine is insufficient to release a measurable amount of iron from ferritin. The liberation of iron from ferritin by xanthine oxidase has important consequences in ischaemia and inflammation. In these circumstances xanthine oxidase, formed from xanthine dehydrogenase, will stimulate the formation of a non-protein-bound iron pool, and the O2(-)-produced by xanthine oxidase, or granulocytes, will be converted by 'free' iron into much more highly toxic oxygen species such as hydroxyl radicals (OH.), exacerbating the tissue damage.

Ferritins↗
PubMed1986

Intraarticular ferritin-bound iron in rheumatoid arthritis. A factor that increases oxygen free radical-induced tissue destruction.

Iron mobilized from ferritin is able to convert superoxide and hydrogen peroxide, which are produced in large amounts in rheumatoid arthritis (RA), to the extremely toxic hydroxyl radical. We have found that synovial fluid ferritin is increased significantly in RA patients compared with levels in controls. The high synovial fluid:serum ferritin ratio is compatible with the hypothesis that synovial fluid ferritin is derived from the synovial membrane. We found no difference in ferritin concentrations in the synovial membranes of RA patients compared with those of controls. Quantitative data on the amount of iron bound to ferritin showed that the level was 2.9 times higher in RA synovial membranes than in those of controls. Moreover, RA synovial fluid contained considerable amounts of iron bound to ferritin. Calculation of the iron saturation of ferritin revealed that RA synovial membranes contained a mean of 2,210 moles of iron per mole of ferritin: a significant elevation when compared with the mean value of 1,500 moles found in the synovial membranes of the controls. The decreased saturation of ferritin in RA synovial fluid, compared with that in the synovial membrane, could be caused by an uncompensated release of iron from ferritin, which has been induced by superoxide that is produced by stimulated granulocytes. The results demonstrate that in the joints of RA patients, sufficient ferritin loaded with iron is available to stimulate oxygen free radical damage.

Arthritis, Rheumatoid↗
PubMed1986

Intracellular and extracellular sulphydryl levels in rheumatoid arthritis.

We detected no difference in the reduced glutathione content of erythrocytes obtained from patients with rheumatoid arthritis (RA) and controls. The stability of glutathione to oxidative stress (cumene hydroperoxide) was also the same. Although measured in the erythrocyte, our results indicate that changes in intracellular reduced glutathione are not involved in the aetiology of RA. Serum from patients with RA had a significantly reduced (p less than 0.01) sulphydryl (SH) concentration (415 +/- 89 (SD) mumol/l) compared with controls (583 +/- 74 mumol/l). This was also valid if the SH groups were expressed per gram of protein. Serum and synovial fluid from RA patients contained similar levels of SH groups (mumol/g protein).

Arthritis, Rheumatoid↗
PubMed1986

Superoxide production by polymorphonuclear leucocytes in rheumatoid arthritis and osteoarthritis: in vivo inhibition by the antirheumatic drug piroxicam due to interference with the activation of the NADPH-oxidase.

The superoxide (O2-) production of stimulated polymorphonuclear leucocytes is increased in patients with rheumatoid arthritis and osteoarthritis compared with controls. Treatment of these different groups with pharmacological amounts of the non-steroidal anti-inflammatory drug piroxicam in vivo resulted in a decrease of about 25% in O2- secretion by isolated granulocytes. In vitro experiments showed that piroxicam inhibits O2- production of granulocytes by interference with the stimulation of the NADPH-oxidase. Piroxicam caused diminished O2- production of membrane fragments if it was present during the stimulation of the NADPH-oxidase of the intact cells. During the actual O2- production of the stimulated membrane fragments piroxicam had no effect. It is concluded that piroxicam is able to inhibit granulocyte O2- production by blocking the activation of NADPH-oxidase, which results in diminished tissue destruction by oxygen free radicals in inflammatory diseases.

Arthritis↗
PubMed1984

Protective factors against oxygen free radicals and hydrogen peroxide in rheumatoid arthritis synovial fluid.

Oxygen free radicals are probably involved in the pathogenesis of rheumatoid arthritis (RA). The enzymes involved in protection against oxygen free radicals and H2O2 (superoxide dismutase, catalase, and glutathione peroxidase) were measured. Superoxide dismutase was not increased, glutathione peroxidase was slightly and catalase was strongly elevated in RA synovial fluid (SF) compared with control SF. Although these enzymes are present in SF, the activities are insufficient to protect against oxygen free radicals and H2O2. In contrast to transferrin, ferritin was increased in RA synovial fluid. Ceruloplasmin was also elevated. When rat liver microsomes were used as a target for oxygen free radicals, serum and SF were both protective. Gel filtration experiments showed that the fraction pattern in which there was maximal protective potential against lipid peroxidation corresponded closely to the level of ceruloplasmin. After removal of ceruloplasmin from serum or SF, about 70% of the protective capacity disappeared. It is concluded that ceruloplasmin is an important protector against oxygen free radicals.

Arthritis, Rheumatoid↗
PubMed1984

Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes. Possible mechanism in inflammation diseases.

During inflammation, the superoxide anion (O-2) and hydrogen peroxide (H2O2) are produced by stimulated polymorphonuclear leukocytes and macrophages. The toxic effects of these reactive oxygen intermediates increase when traces of iron are present, because iron catalyzes the formation of the hydroxyl radical (OH.). Partially saturated iron-binding proteins, such as transferrin and ferritin, are unable to catalyze OH. formation in vitro. Mobilization of iron from these proteins is necessary for iron stimulation of OH. formation. This paper reports that stimulated polymorphonuclear leukocytes mobilize iron from human and horse ferritin, but not from human transferrin. Iron release from ferritin depends on O-2 because it can be prevented by the addition of superoxide dismutase. Catalase and dimethylsulfoxide have no inhibitory effect on iron mobilization. The efficiency of the iron release increases at low levels of O-2 production. Only O-2 produced by granulocytes is sufficient for iron mobilization, because solid potassium superoxide is also able to release iron from ferritin. We propose that this reaction may potentiate the formation of the OH. radical in inflammatory states.

Animals↗