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Biomedical subjects

G J van Kamp

Publications and source records attributed to G J van Kamp.

At least 19 recordsLinked to original sources

Serum tumor marker immunoassays in gynecologic oncology: establishment of reference values.

OBJECTIVE: Our purpose was to establish reference values for six monoclonal antibody-based serum immunoassays applied in patients with carcinoma of the female genital tract. STUDY DESIGN: Sera from 938 healthy women (median age 48.0 years, range 37 to 76 years) were assayed for levels of CA 125, CA 15.3 (two methods), CA M29, CA M26, and mucin-like cancer antigen (MCA). RESULTS: Reference values, defined as those including 95% of healthy controls, were in women with unknown menopausal status as follows: CA 125, 37 U/ml; CA 15.3 (Centocor), 33 U/ml; CA 15.3 (Boehringer Mannheim), 28 U/ml; CA M26, 83 U/ml; CA M29, 13 U/ml; and MCA, 19 U/ml. Postmenopausal values were significantly lower for CA 125 and CA M26 and significantly higher for CA M29 and CA 15.3 (both methods). MCA serum levels were age independent. CONCLUSION: Reference values found were not in accord with those generally applied in gynecologic oncology. In addition, serum levels were influenced significantly by menopausal status (except with MCA).

Adult

Multicenter evaluation of the Abbott IMx CA 15-3 assay.

We describe a new fully automated procedure for the quantitative measurement of CA 15-3: the microparticle enzyme immunoassay (MEIA) technology developed by Abbott Labs. for the IMx automated immunoassay analyzer. The new IMx CA 15-3 test uses two mouse monoclonal antibodies, 115D8 and DF3. The test has a dynamic range to 250 kilounits/L and a minimal detectable dose of CA 15-3 < 0.2 kilounits/L. On dilution, linearity is excellent, with recoveries ranging from 94% to 101%. Studies were conducted at four sites to evaluate the performance characteristics of this assay. The intra- and interassay CVs were < 4.7% and < 5.6%, respectively, and showed a between-laboratory CV < 5.9%. Test results of the Abbott IMx CA 15-3 (y) were correlated with those obtained with the Centocor CA 15-3 RIA (x), a solid-phase heterologous RIA. Linear regression analysis on results for 1973 samples yielded: y = 0.97x - 2.09 (r = 0.9899, Sy/x = 22.2, range 1-4089 kilounits/L).

Animals

Changed transferrin sialylation in Parkinson's disease.

Variation in the sialylation pattern of transferrin was studied in serum and cerebrospinal fluid (CSF) of 90 patients with Parkinson's disease (PD), dementing and non-dementing, de novo and treated, and was compared with the variation observed in a group of 21 age-matched healthy controls. In serum and CSF of PD patients the proportional contribution of the different sialo-transferrins was independent of sex or dementia. However, a significant shift was found towards the more sialylated fractions for serum transferrin in both de novo and treated PD patients. This shift was not observed for CSF transferrin. The contribution of the tau-transferrin fraction, reduced in de novo PD patients, returns on treatment to the level observed for healthy controls. These observations may be important, as the degree of sialylation of transferrin in serum and CSF plays a role in the homeostasis of iron, and suggest that alterations in transferrin sialylation may play a role in the pathophysiology of PD.

Aged

Minor human antibody response to a mouse and chimeric monoclonal antibody after a single i.v. infusion in ovarian carcinoma patients: a comparison of five assays.

The human anti-(mouse Ig) antibody (HAMA) response was measured in serum of 52 patients suspected of having ovarian carcinoma who had received an i.v. injection of either the murine monoclonal antibody (mAb) OV-TL 3 F(ab')2 (n = 28, 1 mg) or the chimeric mouse/human mAb MOv18 (cMOv18; n = 24, 3 mg). Serum samples were taken before injection and 2-3 and 6-14 weeks after administration. A double-antigen or bridging assay was developed to detect responses against both murine as well as chimeric antibodies. In addition, an indirect enzyme-linked immunosorbent assay (ELISA) as well as three commercially available assays were used to study antibody response against the murine antibody OV-TL 3. With both the double-antigen (bridging) assay and the indirect ELISA 1 of the 28 patients (4%) injected with murine OV-TL 3 F(ab')2 showed a HAMA reaction 6 weeks after injection, which was demonstrated to be a mixed anti-isotypic and anti-idiotypic response. None of the 24 patients injected with the chimeric MOv18 showed an anti-chimeric antibody response. The various commercially available assays demonstrated conflicting results. The double-antigen- or bridging assay is a reliable method to detect anti-murine and anti-chimeric antibodies. The assay can be easily adapted for use with human antibodies. The immunogenicity of OV-TL 3 F(ab')2 and cMOv18 in patients is low, making both antibodies candidates for immunotherapy.

Adult

Albumin and immunoglobulin levels in nasal secretions of patients with nasal polyps treated with endoscopic sinus surgery and topical corticosteroids.

BACKGROUND: Nasal polyposis is principally treated by surgery, which may be combined with administration of topical corticosteroids to postpone or prevent recurrences. OBJECTIVE: In this study endoscopic sinus surgery and subsequent use of topical corticosteroids (budesonide) for 1 year was evaluated. METHODS: Clinical data of 41 patients with nasal polyps were evaluated, and their nasal secretions were compared with those of 26 healthy persons (control subjects). RESULTS: The patients had much higher initial total protein, albumin, IgM, secretory IgA (S-IgA) (p < 0.001 for all), and IgG concentrations (p < 0.05) than the control subjects. Treatment resulted in a significant decrease of S-IgA (p < 0.001) within 6 months. IgM and IgG concentrations decreased more slowly (p < 0.001 and p < 0.05 at 1 year, respectively). IgE levels decreased, but we could not demonstrate significance. Relative to total protein levels, the albumin and S-IgA levels decreased within 6 months (p < 0.005 and p < 0.001, respectively). The excretion of all proteins remained higher in patients than in the control subjects, even after 1 year of topical corticosteroid treatment. Clinical evaluation showed slightly higher S-IgA levels in patients with an IgE-mediated allergy than in those without such a condition, and the recurrence rate was highest in the former group (75% vs 48%). CONCLUSION: The data support the hypothesis that inflammatory reactions in the nasal mucosa play a role in the pathogenesis of nasal polyps but also suggest an additional causative factor.

Administration, Topical

Polymorphic epithelial mucin (MUC-1)-containing circulating immune complexes in carcinoma patients.

Circulating immune complexes (CICs) containing polymorphic epithelial mucin (PEM/MUC-1) were found in sera of 24.5% of 151 primary breast carcinoma patients and 18-21.4% of patients with advanced ovarian (n = 56) and breast carcinomas (n = 61), 37% of patients with benign breast tumours, but in only 2.1% of 96 healthy individuals. The incorporation of PEM into CICs affects the detection of circulating PEM in commercial immunoassays such as the CA 15-3 assay, as suggested by a negative correlation between levels of PEM-containing immune complexes (PEM-CICs) and CA 15-3 values, and confirmed by isolation of PEM from CA 15-3-negative sera containing high levels of PEM-CICs. The amounts of PEM masked by human antibodies correspond to significant values of the CA 15-3 assay when monitoring patients for carcinoma. Most antibodies in PEM-CICs were of IgG class, suggesting their specific nature to the PEM epitopes.

Adult

Methylene blue increases myocardial function in septic shock.

OBJECTIVE: To study whether the circulatory changes of human septic shock are mediated in part by nitric oxide. DESIGN: Open-label, nonrandomized clinical trial on the effects of methylene blue, an inhibitor of nitric oxide action. SETTING: Intensive care unit of a teaching hospital. PATIENTS: Nine consecutive patients with documented septic shock and a pulmonary artery catheter in place, after initial resuscitation with fluids, sympathomimetics, and mechanical ventilation. INTERVENTIONS: Hemodynamic and metabolic variables were measured before and then 15, 30, 60, and 120 mins after the start of a 20-min infusion of 2 mg/kg of methylene blue. MEASUREMENTS AND MAIN RESULTS: Patients had a hyperdynamic circulation, and methylene blue increased (p < .01) mean arterial pressure from 84 +/- 18 to 109 +/- 31 mm Hg and cardiac index from 4.7 +/- 0.9 to 5.6 +/- 1.2 L/min/m2, before and 30 mins after starting the methylene blue infusion, respectively. Cardiac filling pressures did not change. In the same time interval, the subnormal systemic vascular resistance index increased (p = .09) and arterial compliance decreased (p < .05). Oxygen delivery and oxygen uptake increased (p < .05) from 714 +/- 188 to 865 +/- 250 mL/min/m2 and from 160 +/- 39 to 186 +/- 44 mL/min/m2, respectively. Except for heart rate, which increased by 11 +/- 8 beats/min (p < .01), variables returned to baseline values at time = 120 mins. CONCLUSIONS: After initial resuscitation from human septic shock, a single dose of methylene blue transiently increases mean arterial pressure and oxygen uptake, associated with a decrease in arterial compliance and increases in myocardial function and oxygen delivery. Hence, nitric oxide may be a mediator of the circulatory changes of human septic shock.

Aged

The second generation CA 125 assays.

Optimal management of ovarian cancer patients can only be provided using the CA 125 serum test for treatment monitoring, early prediction of outcome and early detection of recurrence. The newly introduced second generation CA 125 assays, the Centocor CA 125 II IRMA, the Boehringer Mannheim Enzymun CA 125 II and the BYK Liamat CA 125 II are one-step heterlogous double-determinant solid phase assays that utilize the M11 as capture antibody and the original OC 125 as tracer. The CA 125 II assays will probably replace the original CA 125 assays within a short period of time. For comparison reasons the Abbot IMx CA 125 assay was also included in this study. Highly similar CA 125 distribution patterns were obtained with these new CA 125 II assays. Linear regression analysis in ovarian cancer patients showed the following: Centocor CA 125 II = 0.98 x CA 125 IRMA + 10.7 (r = 0.8717, P < 0.0001), Syx = 89.9; Enzymun CA 125 II = 1.03 x CA 125 + 9.0 (r = 0.8988, P < 0.0001) Syx = 81.8; BYK Liamat CA 125 II = 1.17 x CA 125 IRMA + 0.6 (r = 0.8930, P < 0.0001), Syx = 96.8. Our first technical and clinical evaluation of these three new CA 125 II assays shows their superior analytical performance, in addition to a high qualitative and quantitative correlation with the original CA 125 IRMA.

Biomarkers, Tumor

Biochemical parameters in BAL of sarcoisosis.

UNLABELLED: Sarcoidosis can be presented to the physician as an active or silent disorder, which may resolve or lead to pulmonary fibrosis. Various serum or bronchoalveolar lavage fluid (BAL) markers have been suggested when trying to find one marker or a combination of markers which could be representative of the disease. The aim of the study was to evaluate a number of biochemical markers in comparison to cellular parameters in BAL of 45 patients with active or inactive sarcoidosis, as well as in 44 patients with other disorders and of 10 healthy volunteers. Moreover, in order to get insight into ACE activity in different compartments, ACE values in BAL and serum were compared. In active sarcoidosis BAL-procollagen-III-peptide was significantly increased in contrast to the very low values in inactive disease. In healthy volunteers procollagen-III-peptide levels were below the detection limit. In BAL no significant differences were found for beta-2-microglobulin, hyaluronan or ACE. Laminin in BAL was not detectable. Serum ACE, significantly enhanced in sarcoidosis, was not discriminative between active and inactive disease. IN CONCLUSION: only procollagen-III-peptide in BAL was found to discriminate between active and inactive disease. Besides cell differentiation and T-helper/suppressor cell (CD4/CD8) ratio in BAL, no further biochemical parameters pointing to disease or activity of disease were found.

Adult

Cerebrospinal fluid ferritin levels of patients with Parkinson's disease, Alzheimer's disease, and multiple system atrophy.

Iron is believed to play a role in the pathogenesis of both Parkinson's disease (PD) and Alzheimer's disease (AD). We measured ferritin, which is considered to be the iron storage protein, in CSF of patients with PD, AD, and multiple system atrophy (MSA) as well as control subjects. We found a significant increase in CSF ferritin in AD compared with both PD and age-matched controls. No significant differences were found between PD patients with dementia (PDD) and non-demented PD patients. For non-demented PD patients a positive correlation between CSF ferritin and age was found. Our results may indicate that iron has a role in the pathophysiology of AD.

Age Distribution

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

Urinary epidermal growth factor excretion is correlated to renal function loss per se and not to the degree of diabetic renal failure.

Urinary epidermal growth factor (EGF) excretion is seen as a marker of tubular function, and some studies conclude that EGF excretion can already be reduced early in the development of diabetic renal disease. It is even suggested that EGF could play a role in kidney and glomerular enlargement and hypertrophy in diabetic subjects. We have investigated various groups of subjects, namely healthy controls (n = 5), patients with non-diabetic chronic renal insufficiency (n = 10), and normoalbuminuric (n = 9), microalbuminuric (n = 13) and nephropathic (n = 9) insulin-dependent diabetic subjects. In all subjects glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured using a continuous infusion of 125I-iothalamate and 131I-hippuran, respectively. Diabetic subjects were tested during (near) normoglycaemic conditions. During the renal function test urine was collected for EGF measurement (in ng). With lower GFR values, EGF excretion/min was also lower. GFR correlated well with EGF/min (r = 0.63, p < 0.001). Fractional EGF clearance (EGF/GFR) was comparable in all groups. There was no correlation between urinary albumin excretion rate and EGF excretion in the diabetic subjects (r = -0.18, n.s.) and in all subjects (r = -0.12, n.s.). There was a significant correlation between UAER and GFR (r = -0.51, p < 0.005). No significant correlation could be found between urinary albumin excretion rate (UAER) and EGF/GFR (r = -0.07, n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

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

Serum alpha 1-antichymotrypsin is not a useful marker for Alzheimer's disease or dementia in Parkinson's disease.

We measured serum alpha 1-antichymotrypsin (ACT) levels in patients with Alzheimer's disease (AD), Parkinson's disease (PD), Multiple System Atrophy (MSA) and age-matched controls to evaluate whether serum ACT levels in AD patients were elevated and whether ACT levels in PD patients with dementia differed from those in PD or AD. None of the patient groups displayed an increase in ACT levels. We conclude that serum ACT is not useful as a marker, nor in AD nor in dementia in PD.

Aged

Endothelial vasoactive mediators in preeclampsia.

OBJECTIVE: In recent years an increasing amount of evidence supports the concept that preeclampsia is an endothelial disease. The purpose of our study was to evaluate the extent to which endothelial cell dysfunction is involved in pathophysiology of preeclampsia. STUDY DESIGN: We studied the urinary excretion of thromboxane B2 and 6-keto-prostaglandin F1 alpha and the venous plasma endothelin levels in 23 preeclamptic patients and in control subjects. In six of these patients and in six controls arterial plasma endothelin levels were also measured. In addition, plasma levels of calcitonin gene-related peptide and plasma fibronectin levels were measured. Results were analyzed by Wilcoxon's rank-sum test or signed-rank test. RESULTS: In preeclampsia the urinary thromboxane B2/6-keto-prostaglandin F1 alpha ratio (p < 0.001), venous plasma endothelin levels (p < 0.001), and plasma fibronectin levels (p < 0.001) were significantly elevated compared with normotensive pregnancy. Arterial plasma endothelin levels were significantly higher than venous plasma endothelin levels in normotensive and hypertensive patients (p < 0.05). Calcitonin gene-related peptide levels showed a wide range in normotensive pregnancy and in preeclampsia, but the difference was not significant. CONCLUSIONS: These results confirm the extensive involvement of the endothelium in the pathophysiology of preeclampsia. Preeclamptic vasoconstriction seems to be mediated by an increase in the vasoconstrictor autocoids thromboxane A2 and endothelin. Production of prostacyclin by the vessel wall and endovascular trophoblast might be just a pivotal escape mechanism of the uteroplacental circulation. Calcitonin gene-related peptide appears not to be involved in the pathophysiology of preeclampsia.

6-Ketoprostaglandin F1 alpha

Discordant serum CA 125 values in commercial immunoassays.

The CA 125 assay is from a clinical point of view very well suited to monitor ovarian cancer patients. Although most commercial assay systems include as standards CA 125 preparations derived from the OVCA 433 cell line, the various assay configurations do not produce identical results. The so called cut-off value of 35 U/ml obtained in the original Centocor CA 125 assay appears to be equivalent to CA 125 values ranging as low as 18 U/ml and as high as 53 U/ml in other commercial CA 125 assays now available. Because of these dissimilar results, obtained with different immunoassays, switching from one assay to another during follow-up, should not be tolerated. The newly introduced second generation Centocor CA 125 II IRMA was shown to retain the cut-off values of 35 U/ml and 65 U/ml as defined with the original CA 125 IRMA.

Animals