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S Meijer

Publications and source records attributed to S Meijer.

At least 109 records · Page 6Linked to original sources

Paradoxical changes in organ blood flow after arginase infusion in the non-stressed rat.

Arginine (ARG) is the precursor of nitric oxide (NO), a potent vasodilator. Arginase (ASE) is released following hepatocellular damage, resulting in low plasma ARG levels. The effect of ASE infusion on hemodynamics was studied. Rats received a 20 min ASE or saline infusion, and systemic hemodynamics and organ blood flow were studied, at 30 and 270 min, using radiolabeled microspheres. Compared with control, ASE resulted (30 min) in 1) undetectable ARG levels; 2) higher mean arterial pressure and total peripheral resistance (both p < .05); 3) higher blood flow to the heart, kidneys, stomach, small intestine (all p < .05), and spleen (p < .001); and 4) lower vascular resistance in the heart, kidneys, stomach, and small intestine (all p < .05) and in the spleen (p < .005). At 270 min, ASE rats had similar organ blood flow and higher nitrate levels in urine and plasma (both p < .05) compared with control. We conclude that ASE reduces ARG levels with simultaneous increase in mean arterial pressure and total peripheral resistance. Higher nitrate production, suggesting higher NO formation in the presence of low ARG plasma levels, is paradoxical but could explain the higher blood flow in some organs. The increased total peripheral resistance during higher nitrate formation suggests regional differences in dependency of NO production on plasma ARG levels.

Animals↗

An enzyme-linked immunosorbent assay for the measurement of circulating antibodies to polymorphic epithelial mucin (MUC1).

INTRODUCTION: About one-third of breast and ovarian carcinoma patients have circulating antibodies reactive with polymorphic epithelial mucin (MUC1), either free or bound to immune complexes. While the presence of these immune complexes has prognostic significance in breast cancer patients, the significance of free MUC1 antibodies is less clear. The objective of this study was to develop a reliable assay for the accurate determination of circulating free antibodies to MUC1. MATERIAL AND METHODS: We developed an enzyme-linked immunosorbent assay (ELISA) (PEM.CIg) employing a 60 mer peptide (a triple tandem repeat sequence of the MUC1 peptide core) conjugated to bovine serum albumin and peroxidase-labeled antihuman immunoglobulin G or M antibodies. The assay was standardized and its analytical performance evaluated. A total of 492 serum samples were obtained from 40 healthy men, from 201 healthy women (including 55 women without a history of pregnancy and 45 pregnant women), and (before primary treatment) from 62 benign breast tumor patients and 190 breast cancer patients. MUC1 serum levels were determined with commercial CA 15-3 tests. RESULTS: Circulating antibodies to MUC1 are present both in healthy subjects and in breast cancer patients. The within- and between-assay coefficients of variation were, respectively, 2 and 12% for the IgG determinations and 1.2 and 3% for the IgM determinations. Correlation coefficients for serially diluted serum samples ranged from 0.9998 to 0.9920 for IgG and from 0.9996 to 0.9818 for IgM determinations. The reactivity of serum samples was partially blocked by the addition of various MUC1 peptides and by MUC1 mucin. The inhibiting effect of modified 60 mer peptides suggests the presence of antibodies directed to more than one epitope. CONCLUSIONS: The PEM. CIg assay is a reliable ELISA for measuring free MUC1 antibodies in serum. We are in the process of relating the results obtained in the breast cancer group to disease outcome to evaluate its prognostic significance. In addition, the assay may become a useful tool for vaccine therapy monitoring.

Autoantibodies↗

Sperm penetration assay in predicting successful in vitro fertilization. A meta-analysis.

OBJECTIVE: To determine if the performance of the sperm penetration assay (SPA) is useful in predicting successful in vitro fertilization (IVF). METHODS: A meta-analysis was set up to determine the performance of SPA in the prediction of IVF success. We collected data on 647 patients in 24 studies. For each study, a two-by-two table was constructed from the results of SPA and IVF. RESULTS: The sensitivity and specificity of SPA as compared to IVF were heterogeneous. A summary receiver operating characteristics curve could be estimated, showing that the sensitivity of SPA was only 37%, with a specificity of 95%. Subgroup analysis did not explain the lack of homogeneity. CONCLUSION: Since withholding IVF inappropriately has major consequences, performing SPA is insufficient for selecting patients for treatment with IVF-embryo transfer.

Animals↗

Sentinel node biopsy in melanoma patients: dynamic lymphoscintigraphy followed by intraoperative gamma probe and vital dye guidance.

Biopsy of the first tumor-draining lymph node (sentinel node, SN) is bound to become the procedure of choice in regional staging of melanoma patients. A tumor-negative SN virtually excludes lymphatic metastases and obviates the need for lymph node dissection. The aim of this study was to combine the advantages of three known techniques to improve the yield of successful SN biopsies. A total of 150 drainage areas in 135 patients was evaluated. First, preoperative dynamic and static lymphoscintigraphy was performed after injection of technetium 99m colloidal albumin. In all patients one to three focal accumulations, concordant with SNs, were seen in the lymphatic drainage areas, in 97% within 20 minutes from injection of the tracer. Peroperative identification of the SN, 2 to 24 hours after injection of the tracer, was done with a handheld gamma probe to estimate the optimal site for the small incision and to guide preparation. Vital dye was injected just preoperatively and served to facilitate the final identification and biopsy of the SN. A total of 216 SNs were biopsied. Micrometastases were found in 39 SNs in 30 drainage areas, and in 22 of the 30 of the SN was the only node harboring tumor. In 5 of 30 drainage areas, the SN did not contain blue dye and would not have been found without the gamma probe. Up to now (follow-up 233-691 days) no recurrence has developed in the lymphatic drainage areas where the SN was tumor-free. It was concluded that by combining these three techniques the SN could be detected and excised in all patients. The procedure combines a steep learning curve with high sensitivity.

Biopsy, Needle↗

5-fluorouracil/leucovorin-induced inhibition of thymidylate synthase in normal tissues of mouse and man.

We evaluated the effects of 5-fluorouracil (5FU) and leucovorin (LV) on thymidylate synthase (TS) in normal rapidly dividing tissues, which may contribute to toxic side-effects of treatment with 5FU and LV. TS levels were determined in biopsies of human liver and colon mucosa and murine bone marrow, liver and intestinal mucosa at several time points after administration of therapeutic doses of 5FU or LV/5FU. In murine liver, after treatment with 100 mg/kg 5FU, TS inhibition was significantly higher than after LV/5FU administration (P < 0.001). A similar trend was observed in human liver tissue. Murine intestinal mucosa had TS levels below the limit of detection after 5FU or LV/5FU treatment. In human colon mucosa samples, administration of 500 mg/m2 5FU resulted in a large extent of TS inhibition but the small number of samples did not allow a time- or 5FU-LV/5FU-related evaluation. TS activity in murine bone marrow cells was strongly inhibited to 10% of the control value during 48 h. LV/5FU administration resulted in a slightly higher inhibition. No human bone marrow was available to measure TS levels. Both in mice and humans the most pronounced TS inhibition occurred in the tissue that was involved in dose-limiting toxicity. Therefore it is very likely that TS inhibition in normal tissues contributes to the toxic side-effects of 5FU treatment.

Adult↗

The use of biliary CEA measurements in the diagnosis of recurrent colorectal cancer.

To assess the usefulness of biliary CEA determinations in the diagnosis of recurrent tumour, gallbladder bile was sampled in patients who underwent laparotomy for proven or suspected recurrent colorectal cancer and in control patients. Biliary CEA concentrations in controls were < 5 ng/ml, whereas significantly elevated CEA concentrations were found in the bile of all patients with tumour recurrence. Serum concentrations in these patients were elevated in 77% only. In a series of 12 patients with (a) suspicious lesion(s) on liver imaging but normal serum CEA concentration during follow-up, biliary CEA determination differentiated clearly between metastases and benign lesions. Biliary CEA determination seems to aid detection of tumour recurrence at an early stage and may preclude unnecessary surgery in patients with undefined liver lesions.

Bile↗

Impact of lymphoscintigraphy on sentinel node identification with technetium-99m-colloidal albumin in breast cancer.

UNLABELLED: Identification of the sentinel node by using colloidal tracers and a gamma probe or lymphoscintigraphy could be an effective alternative for the complicated original dye-oriented approach. We studied the sentinel node detection rate using early and delayed imaging in breast cancer patients. METHODS: Thirty-seven patients were imaged 2 hr and 18 hr after peritumoral injection of 99mTc-colloidal albumin. Preoperatively, axillary foci were located with a handheld gamma probe that was also used to isolate radiolabeled nodes from the axillary dissection specimens. The predictive value of the sentinel node for the axillary tumorstatus was evaluated with histological examination. RESULTS: Two and 18 hr after injection, lymphoscintigraphy revealed one to three separate axillary lymph nodes in 33 and 34 patients, respectively. In 30 patients the axillary foci were easily localized with the gamma probe preoperatively. In all 34 patients (92%), with visualized axillary foci, at least one radioactive sample could be retrieved using the gamma probe (total 53 samples). Metastases were found in the sentinel nodes of 11 patients, in seven of 11 being the only tumor-positive lymph node in the axilla. There were no false-negative sentinel nodes. CONCLUSION: The selective targeting and prolonged intranodal retention of 99mTc-colloidal albumin allows successful sentinel node identification in most (92%) patients.

Aged↗

Clinical and technical evaluation of ACS BR serum assay of MUC1 gene-derived glycoprotein in breast cancer, and comparison with CA 15-3 assays.

The mucin glycoprotein-detecting assay CA 15-3 is a valuable tool for monitoring the course of disease in breast cancer patients. Assays of CA 15-3 are based on the use of two MAbs to polymorphic epithelial mucin (PEM). We evaluated the technical and clinical performance of the Chiron ACS BR, an automated competitive chemiluminescence assay using a single MAb, B27.29, and compared the assay's results with those of the Centocor CA 15-3 RIA, the Abbott IMx CA 15-3, and the Boehringer Mannheim Enzymun-Test CA 15-3. The study population consisted of 253 healthy women, 66 patients with benign breast disease, 168 breast cancer patients, and 76 patients with other carcinomas. In the technical evaluation, we assessed the precision and linearity on dilution of the ACS BR assay. Cutoff values (upper limits of values seen in healthy subjects) were determined for all four assays. Agreement between the assays was studied by linear regression analysis. The ACS BR assay gave within- and between-assay CVs of 2.2% and 3.9%, respectively. Three samples from healthy women gave discordant values by ACS BR and were not included in the calculations. All four assays exhibit a highly similar pattern when monitoring breast cancer disease; the closest agreement of values was obtained between ACS BR and Centocor CA 15-3. We conclude that the ACS BR assay is a fast and reliable immunoassay for measuring PEM in serum. Although it detects a slightly different epitope on the PEM molecule than is targeted in other assays, for cancer serum samples it agreed better with the original Centocor CA 15-3 assay than did the other two CA 15-3 assays tested.

Adolescent↗

Low intercellular adhesion molecule 1 and high 5T4 expression on tumor cells correlate with reduced disease-free survival in colorectal carcinoma patients.

The purpose of this study was to investigate the prognostic value of the expression of intercellular adhesion molecule 1 (ICAM-1), leukocyte function antigen 3 (LFA-3), human leukocyte differentiation antigen (HLA)-ABC, HLA-DR, and 5T4 with regard to disease-free survival in Dukes' B and C colorectal carcinoma patients. Forty-one patients (28 Dukes' B and 13 Dukes' C) were entered into this study. Immunocytochemistry was performed on cytospin preparations of enzymatically digested colorectal carcinoma cell suspensions. The frequency of metastases and the duration of disease-free survival were compared between the 25% lowest expressers and the 75% remaining patients for ICAM-1, LFA-3, HLA-ABC, and HLA-DR, and between the 25% highest expressers and the 75% remaining patients for 5T4. Low numbers of ICAM-1-expressing tumor cells were associated with a shorter disease-free survival (P < 0. 001), independent of Dukes' stage. High numbers of 5T4-expressing tumor cells were associated with shorter disease-free survival in Dukes' B patients (P = 0.04). Cox proportional hazard analysis indicated that low numbers of ICAM-1(+) and high numbers of 5T4(+) cells were independent prognostic factors with relative risks of 13. 0 (P = 0.0002) and 4.7 (P = 0.02), respectively. The combination of 5T4 and ICAM-1 marker information identified subgroups of patients with a good (high ICAM-1) or poor (low ICAM-1/high 5T4) prognosis. Neither a lack of HLA-ABC and LFA-3 expression nor the presence of HLA-DR on the tumor cells gave additional prognostic information. These findings demonstrate that low ICAM-1 and high 5T4 expression on tumor cells are prognostic markers, additional to Dukes' stage, for reduced disease-free survival in Dukes' B and C colorectal carcinoma patients.

Aged↗

[Less axillary dissection necessary due to sentinel node biopsy in patients with breast carcinoma].

OBJECTIVE: To determine whether the sentinel node concept is appropriate in patients with breast cancer, notably whether the sentinel node can be identified after peritumoral injection of colloidal 99mTc albumin using lymphoscintigraphy or a handheld gamma probe in the axillary drainage area. DESIGN: Descriptive. SETTING: Academic Hospital Free University, Amsterdam, the Netherlands. METHOD: In 30 consecutive patients with T1 and T2 breast cancer lymphoscintigraphy was performed 2 and 18 hours after peritumoral injection of 40 MBq of colloidal 99mTc albumin injection. Focal accumulations in the axilla were registered and localized in vivo using a handheld gamma probe. All patients underwent axillary lymph node dissection. From each surgical specimen the sentinel node was isolated and examined histopathologically. RESULTS: In 28 of the 30 patients lymphoscintigraphy revealed at least one distinct focal accumulation in the axillary region after 2 and 18 h. In nine women more than one sentinel node was registered: two in six and three in three women. In all 28 patients the node was identified in the surgical specimen by gamma probe. In 19 of the 28 (67%) both the sentinel node and the axillary lymph nodes were without metastasis. Three patients had metastases both in the sentinel and in the other axillary nodes, and in 6 patients (21%) the sentinel node was the only node with metastasis. CONCLUSION: In the majority of breast cancer patients a sentinel node was identified after peritumoral injection of colloidal 99mTc albumin, and with a handheld gamma probe the node could be found in the surgical specimen. In none of the women metastasis was found in other lymph nodes if the sentinel node was unaffected.

Adult↗

[Palliative cryosurgery in rectal carcinoma].

OBJECTIVE: Analysis of palliative cryosurgery in rectal cancer patients. DESIGN: Descriptive. SETTING: Department of surgery, University Hospital Vrije Universiteit, Amsterdam, the Netherlands. METHODS: Ninety-three patients (age: 45-92 years) underwent palliative cryosurgery for primary rectal cancer. They were excluded from surgical resection because of old age, accompanying disease(s), inoperability and the presence of hematogenous metastases. The palliative effect of cryosurgery on local symptoms was classified as good, moderate or none. The duration of palliation was calculated in relation to survival as a palliative index: the number of months of (moderate or good) palliation divided by the number of months of survival from the start of the treatment, multiplied by 100%. RESULTS: In 58 patients (62%) there was complete relief of local symptoms with a palliative index of 87%. In 13 patients (14%) palliation was moderate and in 22 patients (24%) no palliation was achieved. The 50% survival duration in the 58 patients was 37 months. Especially symptoms of blood and/or mucous discharge could be easily alleviated. Good alleviation of local symptoms was associated with the extent of the primary tumour process. Palliative effect could be assessed after a few treatments. Patients with circular rectal tumours seldom had long term palliative effects of cryosurgery. CONCLUSION: Cryosurgery for rectal cancer is a simple and safe treatment. It should be considered for alleviation of local symptoms in patients with rectal cancer who are unsuitable for radical surgery.

Aged↗

Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome.

Plasma interleukin-1 (IL-1) activity is modulated in part through the simultaneous appearance of several inhibitors of IL-1 action, including interleukin-1 receptor antagonist (IL-1ra) and the soluble IL-1 type II receptor (IL-1RII). However, little is known concerning the plasma appearance of these inhibitors in patients following operative trauma or those with sepsis syndrome. In the present report, plasma IL-1beta, IL-1ra, and soluble IL-1RI and IL-1RII concentrations were evaluated in 118 patients with sepsis syndrome or after elective operative trauma. Plasma concentrations of IL-1ra increased significantly following elective operative repair of thoraco-abdominal and abdominal aortic aneurysms, and after bowel resection for inflammatory bowel disease, but did not increase after laparoscopic cholecystectomy. Plasma IL-1ra levels were also elevated in patients with sepsis syndrome. In contrast, soluble IL-1RII levels were only increased in patients after operative repair of thoraco-abdominal aortic aneurysms and in sepsis syndrome, whereas concentrations were unaffected by the other more modest surgical procedures. Plasma IL-1RI concentrations decreased in all postoperative patients in the first 24 hours after surgery. We conclude that both plasma IL-1ra and soluble IL-1RII concentrations often increase in sepsis and following some operative trauma. Less severe operative trauma increases the plasma concentration of only IL-1ra, whereas both IL-1ra and soluble IL-1RII are increased in patients with sepsis syndrome or following thoraco-abdominal aneurysm repair.

Adult↗

Prognostic value of negative intraoperative ultrasonography in primary colorectal cancer.

The risk of developing recurrent tumour was assessed in a group of 85 patients with primary colorectal cancer who had a negative intraoperative ultrasonographic examination at the time of primary tumour resection. At a median follow-up of 40 months liver metastases had developed in 14 patients (16 per cent). Dukes classification of the primary tumours was stage A, B and C in one, three and ten patients respectively. The interval between primary tumour resection and detection of metastases varied from 6 to 24 months but all became evident within 2 years. Sixteen patients (19 per cent) presented with extrahepatic recurrence, one of whom also developed liver metastases. A negative intraoperative ultrasonographic examination did not prove to be a favourable prognostic factor which allowed exclusion from follow-up or adjuvant chemotherapy.

Adult↗

Role of Kupffer cells in arresting circulating tumor cells and controlling metastatic growth in the liver.

Metastasis to the liver is a common event in clinical oncology. Blood-borne tumor cells (TCs) arriving to the liver sinusoids run into a special vascular bed. The lining of liver sinusoids is shared by Kupffer cells (KCs) and endothelial cells. KCs, liver-fixed macrophages, are responsible for detection and removal of "non-self" particles. To investigate their role in arresting blood-borne TCs and controlling tumor growth, we injected a syngeneic colon carcinoma cell line into a mesenteric vein of two groups of rats; one group was without Kupffer cells and the other normal controls. We removed the liver of these animals at different time intervals and performed immunohistochemical analysis with monoclonal antibodies (MoAbs) against our tumor cell line, three macrophage subpopulations, natural killer cells, and B and T lymphocytes. Additionally, we showed in vitro spontaneous cytotoxicity of KCs against our tumor cell line. Results suggest that KCs play a relevant role in arresting circulating TCs at the liver sinusoid, although it is limited to a small number of malignant cells. They also seem to play a major role in clearing neoplastic cells from the liver parenchyma, in controlling tumor growth in the very early stages of metastatic development, and in modulating the host immune response to cancer cells.

Animals↗