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Biomedical subjects

A E Meinders

Publications and source records attributed to A E Meinders.

At least 127 records · Page 7Linked to original sources
PubMed1995

Reduction of synovial inflammation after anti-CD4 monoclonal antibody treatment in early rheumatoid arthritis.

OBJECTIVE: To study the effect of chimeric anti-CD4 monoclonal antibody (MAb) therapy on synovial inflammation, in order to interpret the clinical experience with anti-CD4 treatment. METHODS: The immunohistologic features of synovial biopsy specimens before and 4 weeks after anti-CD4 MAb (cM-T412) therapy were studied in patients with rheumatoid arthritis. The patients received intravenous doses of either placebo (n = 1) or 10 mg (n = 4), 25 mg (n = 2), or 50 mg (n = 1) of cM-T412 daily for 5 consecutive days. RESULTS: Although the patients did not experience clinical improvement, significant decreases in the number of circulating CD4+ cells, the degree of synovial inflammatory infiltration, and the mean scores for expression of adhesion molecules were found in the 7 patients 4 weeks after receiving cM-T412. The scores for infiltration with CD4+ and other inflammatory cells were particularly reduced following treatment with either 25 mg or 50 mg cM-T412. Cytokines, such as interleukin-1 beta and tumor necrosis factor alpha, could still be detected in the synovial tissue after treatment. CONCLUSION: The decline in the numbers of inflammatory cells and adhesion molecules in synovial tissue after CD4+ cell depletion supports the view that CD4+ T cells orchestrate local cellular infiltration. The lack of clinical effect of anti-CD4 therapy might be explained by an insufficient decrease in the number of synovial CD4+ cells and by the persistence of cytokines. Determination of whether more adequate dosing would lead to a clinical improvement must await further study.

Adult↗
PubMed1995

Expression of adhesion molecules in early rheumatoid synovial tissue.

The objective of this paper is to define the expression of adhesion molecules in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration. Antibodies against adhesion molecules were used for immunohistochemistry to examine ST sections from 11 patients with early RA ( < 1 year), 14 patients with long-standing RA ( > 5 years), and 15 patients with osteoarthritis (OA). Increased cellular infiltration and increased expression of E-selectin, ICAM-1, VCAM-1, PECAM-1, VLA-4, and Mac-1 were found in ST from patients with RA compared to ST from patients with OA. The immunohistological findings were similar for the different stages of RA. The upregulation of adhesion molecules in ST of patients with RA of < 1 year's duration suggests the activation of chronic inflammatory processes in these patients. Therefore, the mechanisms by which therapies directed toward these adhesion molecules exert their effects are likely to be similar for patients with so-called early RA and patients with long-standing RA.

Aged↗
PubMed1995

Early jugular bulb oxygenation monitoring in comatose patients after an out-of-hospital cardiac arrest.

OBJECTIVE: To determine the role of early jugular bulb oxygenation monitoring in comatose patients after cardiac arrest. DESIGN: Prospective sequential study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Thirteen patients comatose after out-of-hospital cardiac arrest. INTERVENTIONS: A standard hemodynamic protocol. MEASUREMENTS AND RESULTS: Jugular bulb oxygen saturation levels and oxygen extraction ratios could not discriminate between patients with good (6) and poor (7) cerebral outcome. This was also true for the jugular bulb-arterial lactate difference. Survivors had significantly higher overall oxygen transport values than non-survivors. CONCLUSIONS: Jugular bulb oxygenation monitoring during the first few hours after cardiac arrest cannot reliably discriminate between comatose patients with a good and poor cerebral outcome. Further studies with an extended monitoring period are thus required.

Adult↗
PubMed1995

Predictive value of tetrapolar body impedance measurements for hydration status in critically ill patients.

OBJECTIVE: To design and evaluate a simple and rapid method to predict body hydration status in critically ill patients. DESIGN: Prospective, consecutive sample. SETTING: Medical intensive care unit of a university hospital. PATIENTS: 31 consecutive patients. METHODS: All patients were classified daily for hydration status by the attending physician based on clinical impression, weight changes and laboratory measurements. The hydration status was scored as 'dehydrated', 'euvolemic' or 'edematous'. The total body impedance was measured daily by a tetrapolar impedance technique. RESULTS: Resistances > 700 omega were found in dehydrated subjects and resistances of < 400 omega in edematous patients. Weight gain was observed in dehydrated and weight loss in edematous patients. A discriminant analysis was used to create a predictive model for hydration using the daily impedance and weight measurements. If a cutoff point of 60% for the predicted classification was used to categorize the patient's hydration as dehydrated, euvolemic and edematous, no false positive predictions were observed for the dehydrated or the edematous state. CONCLUSION: Impedance measurements are in close agreement with the clinical impression of hydration of critically ill patients. Future investigations must elucidate the clinical importance.

Adolescent↗
PubMed1995

Respiratory failure in leptospirosis (Weil's disease).

Two patients with leptospirosis (Weil's disease), with acute respiratory failure necessitating mechanical ventilation, are described. Adult respiratory distress syndrome (ARDS) in one patient and profuse pulmonary bleeding in the other were the respective causes of respiratory failure. One patient died after developing the multiple organ dysfunction syndrome (MODS), the other patient recovered completely. Respiratory failure is an uncommon complication of leptospirosis and is due to severe pulmonary bleeding and/or ARDS.

Adult↗
PubMed1995

Improved outcome for patients with a cardiac arrest by supervision of the emergency medical services system.

BACKGROUND: The outcome for patients with an out-of-hospital cardiac arrest can only be improved through optimal pre-hospital therapy by the emergency medical services (EMS) system. So far it is not clear if physician supervision of the EMS system is necessary for an optimal result. METHODS: In a retrospective and prospective case series we describe the changes in outcome for patients with an out-of-hospital cardiac arrest after the implementation of limited physician supervision of the EMS system. We also analysed the factors that were responsible for these changes. RESULTS: We studied 479 consecutive patients with an out-of-hospital cardiac arrest. In the pre-intervention period, the survival rate for patients with an out-of-hospital cardiac arrest was 13%. This increased to 21.6% when physician supervision was implemented (p = 0.013). This increase in survival coincided with an improvement in pre-hospital advanced cardiac life support with an increase in the number of patients who arrived with a stable cardiac rhythm in the emergency department (p < 0.001). CONCLUSIONS: Limited physician supervision of an EMS system in a non-metropolitan area may improve the outcome for patients with an out-of-hospital cardiac arrest.

Adult↗
PubMed1995

Release of tumor necrosis factor: an innate host characteristic that may contribute to the outcome of meningococcal disease.

Tumor necrosis factor (TNF) plays a pivotal role in meningococcal disease. The TNF response to endotoxin, however, differs between individuals and can be determined in whole blood samples ex vivo. The release of TNF in whole blood samples from 50 survivors of meningococcal disease 6-58 months after hospital discharge was studied. The TNF response was higher in patients who had experienced a moderately severe disease course compared with patients with a mild course. The TNF response was low again in the survivors of fulminant disease, who on original hospital admission presented with risk factors exposing them to a high chance of mortality (50% overall). On admission, the patients who did not survive had initial TNF levels three times higher than those in survivors with a clinical disease presentation of similar severity. Overall interpretation of these findings is that the innate TNF response may contribute to the outcome of meningococcal disease.

Adolescent↗
PubMed1995

Hypoxia-induced arterial endothelin does not influence peripheral vascular tone.

The effect of hypoxia (SpO2 80%) on the arteriovenous production of endothelin-1 (ET) in the forearm was investigated in six healthy volunteers. In eight other subjects the local vascular effects of a low physiologic dose of intra-arterially administered ET (0.5 pg/kg/min) was studied during normoxia. Forearm blood flow (FBF) was measured by venous occlusion plethysmography, and arterial and venous plasma concentrations of ET were measured. FBF was not significantly influenced during hypoxia. After 15 min of hypoxia the arterial plasma level of ET increased from 2.5 +/- 0.1 to 3.3 +/- 0.3 ng/L (p < 0.05), whereas the venous plasma level remained unchanged. Intra-arterial infusion of ET increased the arterial plasma level of ET in the forearm from 2.2 +/- 0.3 to 4.9 +/- 0.4 ng/L. This increase in ET concentration did not influence FBF. It is concluded that hypoxia is a stimulus for ET release from the pulmonary vascular bed and that the resulting increase arterial plasma ET level does not influence peripheral vascular tone.

Adult↗
PubMed1995

beta-Adrenergic receptors contribute to hypoxaemia induced vasodilation in man.

1. It was the aim of the present study to investigate the role of the beta-adrenergic receptor in hypoxaemia induced vasodilatation in the human forearm. 2. The study was performed in 12 non-smoking male volunteers. In six subjects the local vascular effects of intra-arterially (i.a.) infused propranolol (0.1 mu kg-1 min-1) was determined during normoxaemia and hypoxaemia (peripheral oxygen saturation; SpO2 80%), and compared with the contra-lateral (control) arm. beta-adrenergic receptor blockade by propranolol was confirmed by i.a. infusions of adrenaline. In six other subjects the effects of incremental hypoxaemia (SpO2 90, 85, 80%) on forearm- and finger blood flow was investigated. A difference between these vascular beds is the absence of vascular beta-adrenergic receptors in the finger. Forearm- and finger blood flow were measured by venous occlusion plethysmography. Plasma levels of (nor-)adrenaline were determined in both arterial and venous blood samples. Hypoxaemia was attained by gradual decompression of a hypobaric chamber and individually adjusted. 3. During normoxaemia the single infusion of propranolol did not influence forearm vascular resistance. In contrast, during hypoxaemia a net vasoconstriction was observed in the arm treated with propranolol, which was significantly different (P = 0.009) from the vasodilatation in the control arm (mean difference in response 40%; 95% confidence interval 13.2-66.8). The net arterio-venous spillover of noradrenaline from the forearm increased after the first 15 min of hypoxaemia (P < 0.05) and returned to baseline in the next 15 min. Arterial and venous plasma levels of adrenaline during hypoxaemia remained unchanged compared with normoxaemia. In the second set of experiments incremental levels of hypoxaemia induced a vasoconstriction in the finger, which was significantly different (P = 0.025) from the vasodilatation in the forearm (mean difference in response 300%; 95% confidence interval 63-537). 4. The data indicate that beta-adrenergic receptors contribute to hypoxaemia induced vasodilatation, despite unaltered adrenaline plasma concentrations.

Adult↗
PubMed1994

Identification of virilizing adrenal tumors in hirsute women.

BACKGROUND: Hirsutism in women is usually caused by benign adrenal or ovarian disorders, but it can also be caused by adrenal carcinoma. The most effective way to identify such carcinomas is not known. METHODS: We measured serum and urinary steroids before and after the administration of 3 mg of dexamethasone per day for five days in 14 hirsute women with histologically proved adrenal tumors (12 adrenal carcinomas and 2 adrenal adenomas) and in 73 women with hirsutism of non-neoplastic origin. RESULTS: All the women with adrenal tumors had elevated basal serum concentrations of testosterone or dehydroepiandrosterone sulfate, as compared with 36 of the 73 women with non-neoplastic hirsutism (sensitivity, 100 percent; 95 percent confidence interval, 77 to 100; specificity, 50 percent; 95 percent confidence interval, 38 to 62). After the administration of dexamethasone, serum dehydroepiandrosterone sulfate concentrations and urinary 17-ketosteroid excretion decreased to values similar to those in normal women in all the women with non-neoplastic hirsutism, but in none of the 12 with adrenal tumors who were tested. All the women who did not have adrenal tumors had serum cortisol concentrations below 3.3 micrograms per deciliter (90 nmol per liter) after dexamethasone administration, whereas in all 12 patients tested who had tumors the values were higher. The suppression of serum dehydroepiandrosterone sulfate and cortisol and urinary 17-ketosteroid excretion excluded the likelihood of adrenal tumors with a sensitivity of 100 percent (95 percent confidence interval, 74 to 100) and a specificity of 100 percent (95 percent confidence interval, 89 to 100). CONCLUSIONS: Among women with hirsutism, an adrenal tumor is unlikely if the patient has normal basal serum concentrations of testosterone and dehydroepiandrosterone sulfate. In women in whom these concentrations are elevated, a tumor is unlikely if the serum concentration of dehydroepiandrosterone sulfate and urinary 17-ketosteroid excretion are in the normal basal range and the serum cortisol concentration is less than 3.3 micrograms per deciliter after the administration of dexamethasone.

17-Ketosteroids↗
PubMed1994

Granzyme-positive cytotoxic cells are specifically increased in early rheumatoid synovial tissue.

OBJECTIVE: To define the expression and the phenotype of granzyme (Gran) A and B positive cytotoxic cells in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration and activity. METHODS: Using antibodies against GranA and GranB, which serve as markers of activated natural killer (NK) cells and cytotoxic T lymphocytes, ST sections from 10 patients with early RA, 10 patients with longstanding RA, and 10 patients with osteoarthritis were examined. The phenotype of Gran+ cells was determined with double-labeling techniques. RESULTS: Gran+ cells, the majority of which were NK cells, were found in ST from patients in all groups. Several of these cells did not express the surface markers CD16, CD56, and CD57. The highest ST expression of GranB was found in patients with early RA. In RA patients, there was a positive correlation of GranB expression with serum levels of acute-phase reactants, but not with histologic scores for inflammation. CONCLUSION: Gran+ cells are mainly NK cells, a substantial proportion of which do not express conventional NK cell surface markers. GranB expression is specifically increased in the synovial tissues of patients with RA of short duration.

Aged↗
PubMed1994

Expression of granzymes A and B in synovial tissue from patients with rheumatoid arthritis and osteoarthritis.

Granzymes A and B are serine proteinases which are stored in the granules of activated cytotoxic T cells and NK cells. Expression of these granzymes by cytotoxic cells in tissues can be used as an activation marker for these cells. To investigate a possible role of cytotoxic lymphocytes in rheumatoid arthritis (RA) and osteoarthritis (OA), we assessed the expression of granzymes A and B by cytotoxic lymphocytes in synovial biopsies from five RA and five OA patients using mAb specific for these serine proteinases. In three of the five RA patients but also in two of the five OA patients granzyme A- and B-expressing lymphocytes were observed in the synovium. Double-labeling immunohistochemical techniques revealed that up to 75% of the granzyme-positive synovial lymphocytes had the CD16+ or CD56+ natural killer cell phenotype. Less than 5% were CD3+, CD8+ cytotoxic T cells, whereas in some patients the phenotype of up to 50% of these cells could not be identified. The presence of granzymes A and B in the synovium of both RA as well as OA patients was confirmed on the molecular level in a second group of 11 RA and 5 OA patients using the polymerase chain reaction. Thus, expression of granzymes A and B occurs in the synovium in patients with RA as well as those with OA. These proteins are mainly expressed by NK cells that may therefore play a role in the pathogenesis of these diseases.

Aged↗
PubMed1994

Insulin-induced decline of plasma amino acid concentrations in obese subjects with and without non-insulin-dependent diabetes.

Obesity-associated hyperaminoacidemia is traditionally interpreted as a consequence of insulin resistance. We performed two different experiments to investigate the effects of both obesity-associated insulin resistance and the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM) on amino acid metabolism. In the first experiment, we measured postabsorptive amino acid concentrations and their decline in response to an oral carbohydrate load in 19 obese nondiabetic women and 19 normal-weight nondiabetic controls. Obese subjects were more resistant to insulin with respect to its effects on glucose metabolism than normal-weight controls, as calculated by the method described by Matthews. However, postabsorptive plasma concentrations of the so-called large neutral amino acids (LNAA), namely phenylalanine, tyrosine, valine, leucine, and isoleucine, and their decrease in response to carbohydrate consumption were similar in both groups. In the second experiment, we compared the decrease of plasma concentrations of LNAA during a euglycemic, hyperinsulinemic clamp in obese subjects with and without NIDDM. Peripheral glucose uptake (PGU) was more impaired in NIDDM subjects compared with obese controls. Furthermore, hepatic glucose production (HGP) was less attenuated by insulin infusion in NIDDM than in control subjects. Postabsorptive plasma LNAA concentrations were not different in the two groups. Values obtained in either group were not different from the postabsorptive concentrations in the normal-weight control subjects of experiment 1. All amino acid levels decreased substantially in response to insulin infusion. The magnitude of the decrease was not significantly different in the two groups, except for a slightly greater decrease of the plasma isoleucine concentration in obese control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗