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Biomedical subjects

S Meijer

Publications and source records attributed to S Meijer.

At least 127 records · Page 7Linked to original sources

Effect of intraperitoneal administration of granulocyte/macrophage-colony-stimulating factor in rats on omental milky-spot composition and tumoricidal activity in vivo and in vitro.

Milky spots in the greater omentum are small accumulations of leucocytes that consist mainly of macrophages and have recently shown to be a selective dissemination site of intraperitoneal (i.p.) inoculated tumour cells. However, milky-spot macrophages show tumoricidal activity and may, therefore, be an excellent source of effector cells suited for local immunotherapy. In the present study we first examined whether granulocyte/macrophage-colony-stimulating factor (GM-CSF) treatment of isolated milky-spot macrophages affects the cytotoxicity against syngeneic colon carcinoma cells (CC531) in vitro. Secondly, we studied the influence of intraperitoneal GM-CSF administration on the number and antitumour activity of milky-spot and peritoneal macrophages. All studies were performed in Wag/Rij rats in which a syngeneic colon carcinoma cell line (CC531) is available. The results of the in vitro study showed that GM-CSF treatment of the omental macrophages led to an increased cytotoxicity against the tumour cell line. Intraperitoneal administration of 1000 U GM-CSF daily for 7 consecutive days demonstrated both an enhanced antitumour activity of the milky-spot macrophages and an increase in the milky-spot macrophage population. An increase in the proliferative capacity, according to bromodeoxyuridine incorporation, was shown in the milky-spot macrophages. Taking into account both the enhanced macrophage number and their enhanced activity upon i.p. GM-CSF treatment, the milky-spot macrophages may provide a rationale for local intraperitoneal immunotherapy in the prevention of intra-abdominal tumour growth.

Animals↗

Humoral immune response to polymorphic epithelial mucin (MUC-1) in patients with benign and malignant breast tumours.

To investigate the clinical significance of an immune response to the MUC-1 encoded polymorphic epithelial mucin (PEM) breast cancer, circulating immune complexes containing PEM (PEM.CIC) were measured in sera from 96 healthy women, in pretreatment serum samples from 40 patients with benign breast tumours and from 140 patients with breast cancer and in serum samples from 61 breast cancer patients with recurrent or progressive disease. PEM.CIC were measured using a sandwich enzyme-linked immunoassay, and PEM serum levels were measured with CA 15.3 IRMA (Centocor Inc., Malvern, Pennsylvania, U.S.A.). Cut-off levels used for PEM.CIC and CA 15.3 were 120 Optical Density Units (O.D.) x 10(3) and 30 U/ml, respectively. In benign tumours, positivity for PEM.CIC was 37.5% (15/40). 36 of the 140 patients (25.7%) in the breast cancer pretreatment group had elevated PEM.CIC values. In patients with advanced metastatic disease, positivity for PEM.CIC was 18% (11/61). PEM.CIC was elevated in 32% (24/74) of node-negative patients, but only in 20% (12/59) of node-positive patients and absolute values were higher in node-negative patients (Mann-Whitney U test, two-tailed P = 0.0168). There was an inverse correlation between positivity for PEM.CIC and extent of disease: while 3 of the 6 patients with a carcinoma in situ were positive, only 1 of the 15 patients with more than five nodes involved had elevated levels of PEM.CIC. All 7 patients with distant metastases at first diagnosis were PEM.CIC negative. 28 out of 133 patients had a recurrence during the observation period (median 55 months, range 27-84 months). 23 of these 28 patients (82%) were PEM.CIC negative at the moment of first diagnosis. None of the patients with pretreatment elevation of both PEM.CIC and CA 15.3 (n = 13) relapsed. Our preliminary clinical results suggest that a humoral immune response to PEM protects against disease progression, and further support the idea of using synthetic peptides or glycopeptides containing the immunogenic core of the mucin as cancer vaccines.

Adult↗

Lack of specific renal haemodynamic effects of different doses of dopamine after infrarenal aortic surgery.

Dopamine is administered frequently in the operating theatre and intensive care unit patients undergoing mechanical ventilation with the aim of specifically enhancing renal blood flow. In an uncontrolled, open study, we administered sequentially different doses of dopamine (0, 2, 4, 8 and 0 microgram kg-1 min-1) during a 1-h period each. Systemic haemodynamic and renal haemodynamic variables were measured simultaneously using a pulmonary artery catheter and radiopharmaceuticals, respectively. We studied seven haemodynamically stable patients (mean age 66 yr), with a serum creatinine concentration < 160 mumol litre-1, after elective infrarenal abdominal aortic reconstruction. All patients received extradural analgesia with bupivacaine and sufentanil, and none had a previous history of heart failure. Dopamine induced a dose-dependent increase in cardiac index which returned to baseline after cessation of the dopamine infusion. Glomerular filtration rate (GFR) increased with all doses of dopamine, whereas renal blood flow (RBF) increased significantly only with the 2- and 4-microgram kg-1 min-1 doses. However, the ratio RBF/cardiac output remained unchanged with the 2- and 4-microgram kg-1 min-1 doses, but decreased with 8 micrograms kg-1 min-1 from 14 (1.5)% to 10 (1.3)%. We conclude that dopamine increased RBF and GFR as a result of an increase in cardiac output.

Aged↗

Ingestion of Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli by human peritoneal mesothelial cells.

In the present study we examined whether mesothelial cells can ingest and digest bacteria. The results showed that all strains were ingested. Ingested staphylococci proliferated abundantly, and only a few were digested. Escherichia coli, however, was digested during the first 8 h, whereafter the mesothelial cells disintegrated and proliferation of bacteria could be observed. The clinical implications of these findings are discussed.

Cells, Cultured↗

Detection of occult liver metastases by measurement of biliary carcinoembryonic antigen concentrations.

OBJECTIVE: To assess whether biliary CEA concentrations can be used as early markers of occult liver metastases in patients with colorectal cancer. DESIGN: Consecutive open study. SETTING: University hospital, The Netherlands. SUBJECTS: 76 patients with a primary colorectal carcinoma (group 1) and 19 patients who had recently undergone a curative resection of a locally advanced carcinoma (group 2). INTERVENTIONS: Bile sampling by transhepatic puncture of the gallbladder. MAIN OUTCOME MEASURE: Recurrence of tumour. RESULTS: Twenty-one of the 76 patients (28%) with primary colorectal carcinoma had liver metastases; all had a raised biliary CEA concentration. Of the remaining 55 patients 39 (71%) also had raised CEA concentrations. At a median follow-up of 30 months, only seven patients had developed liver metastases, indicating a high number of false-positive results. In Group 2 7/19 patients (37%) had a CEA concentration above the cut-off point. Six of them developed recurrent tumour; 2 patients had liver metastases and 4 others had extrahepatic recurrences. None of the 12 patients with biliary CEA concentrations within the reference range has developed recurrent tumour. CONCLUSION: Biliary CEA concentrations do not predict the presence of occult liver metastases if bile samples are taken during resection of the primary tumour. If samples are taken some time afterwards, a raised CEA concentration seems to predict recurrence at an early stage, either in or outside the liver.

Adult↗

Renal function influences interleukin-8 background production by cultured human mesothelial cells.

Previous studies have demonstrated that mesothelial cells (MC) are important in the local host defense system of the peritoneal cavity. Most studies on the function of MC are performed on MC derived from material of patients with normal renal function (NRF). The aim of the present study was to examine differences in interleukin (IL)-8 expression by MC from patients with NRF and from patients with end-stage renal disease (ESRD). Therefore, MC were isolated from the omentum and pleural exudate of patients with NRF, from spent effluent of stable peritoneal dialysis (PD) patients, and from omentum obtained during catheter implantation prior to PD treatment. MC were stimulated with increasing doses of IL-1 beta or tumor necrosis factor-alpha for 24 hours, after which the supernatant was analyzed for IL-8 content. The IL-8 background level of MC isolated from patients with NRF was significantly lower than the IL-8 background level of MC derived from patients with ESRD. Although IL-8 production appeared to be higher in the ESRD MC, this difference was not significant after stimulation. While the overall immunity is depressed in uremia, MC are activated. The relatively high background of IL-8 might lead to an insensitivity of neutrophils by blocking the receptors and explain their impaired chemotaxis in uremia.

Adult↗

The impact of dynamic lymphoscintigraphy and gamma probe guidance on sentinel node biopsy in melanoma.

In cutaneous melanoma, biopsy of the first tumour-draining lymph node (sentinel node, SN) may replace routine elective lymph node dissection (ELND). Even in experienced hands the original technique using vital dyes fails to localise the SN in 20% of cases. In this study we investigated whether the procedure benefits from lymphoscintigraphy and the use of a gamma probe. In 41 patients technetium-99m-colloidal albumin was injected intracutaneously around the scar of the excised tumour. This was followed by dynamic and late static imaging. The first focal accumulation was assumed to be the SN. In all patients at least one SN was found, in 95% within the first 20 min. By showing multiple or ramifying lymphatic channels, dynamic lymphoscintigraphy differentiated between spill and multiple SNs. In all cases the initial focus retained the highest fraction of radioactivity for at least 18 h. The gamma probe was especially useful in the axilla and neck, where it accurately showed the optimal incision site and facilitated the search for deep-seated nodes. Gamma probe-localised SNs were dye-positive in 93% of cases. The SN contained metastases in 20% of the patients. Only in these patients was ELND performed, which revealed that the SN had been the only metastatic node in four of eight cases. We conclude that dynamic lymphoscintigraphy is essential for SN localisation, that tracer kinetics allow flexible timing of surgery, and that the surgical procedure benefits from use of the gamma probe.

Adolescent↗

Iodine-131 Hippuran for the estimation of renal plasma flow: requirements for radiochemical purity.

For many years iodide-131 Hippuran has been used as a tracer to measure effective renal plasma flow (ERPF). Because of the low renal clearance of free 131I-iodide and the inability to count it separately from 131I-Hippuran, free 131I-iodide will lower the calculated 131I-Hippuran clearance, resulting in a lower estimated ER-PF. This study was performed to establish the maximum allowable radiochemical impurity of free 131I-iodide in 131I-Hippuran preparations for ERPF measurements in continuous clearance studies. A known amount of 123I-iodide was added to the (131I-iodide-free) 131I-Hippuran solution used for continuous infusion clearance studies in nine patients. 123I-iodide activity was used because it can be counted separately from 131I-Hippuran in the infusion solutions and plasma samples while it behaves exactly like 131I-iodide, so that the results obtained with 123I-iodide can be extrapolated to 131I-iodide. After performing the clearance studies, the ERPF was calculated firstly with 131I-Hippuran activity only (= true ERPF) and secondly including the free radioactive iodide activity (= false ERPF) in the clearance formula. As expected, if free 131I-iodide is present in the infusion solution, its concentration in plasma will be highest at the end of the clearance study. The 131I-iodide concentration in plasma relative to the 131I-Hippuran concentration will be higher in patients with high ERPF values.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

The effects of ibopamine on glomerular filtration rate and plasma norepinephrine remain preserved during prolonged treatment in patients with congestive heart failure.

UNLABELLED: In acute studies ibopamine, an a selective dopamine agonist, induces moderate increases of GFR and ERPF, and a fall in plasma norepinephrine levels in patients with congestive heart failure (CHF). We evaluated acute and chronic effects of ibopamine on renal haemodynamics, sodium excretion, PRA, plasma aldosterone (ALD) and norepinephrine levels in an open controlled study in 10 patients aged (51-79 years) with mild CHF, NYHA class II-III. All patients used digoxin and frusemide. After a control study day, the second study day involved the administration of 100 mg ibopamine. Subsequently the patients continued to take ibopamine 100 mg three times daily for one month, at which time the chronic effects were measured on the third study day. RESULTS: On the second day ERPF rose from a baseline of 288 +/- 32 to a mean of 308 +/- 32 ml.min-1 x 1.73 m-2 (P < 0.05) during the 4 h after the first administration of ibopamine and GFR rose from 77 +/- 8 to a mean of 84 +/- 8 ml.min-1 x 1.73 m-2 (P < 0.05). The ratio GFR/ERPF, representing the filtration fraction (FF) remained unchanged. On the third study day GFR and ERPF at baseline were similar to those before ibopamine treatment. After the acute on chronic administration we observed an increase in GFR (from 76 +/- 6 to a mean of 85 +/- 7 ml.min-1 x 1.73 m-2 (P < 0.05)), and in ERPF (from 279 +/- 27 to a mean of 293 +/- 29 ml.min-1 x 1.73 m-2 (P < 0.05)). Plasma norepinephrine levels fell from 2.63 +/- 0.48 to 1.92 +/- 0.27 nmol.l-1 (P < 0.05) after the acute administration of ibopamine, and remained unchanged after the acute on chronic ibopamine administration (C: 1.80 +/- 0.42 nmol.l-1). No changes in sodium excretion were observed, either in blood pressure, heart rate, PRA or ALD. We conclude that renal function is preserved during chronic ibopamine treatment and the acute moderate increase of ERPF and GFR after a single dose of 100 mg of ibopamine is still present after one month of treatment with ibopamine in patients with CHF. Ibopamine lowered plasma norepinephrine levels in our patients with CHF, and these values remained unchanged after the acute on chronic administration of ibopamine.

Adult↗

Renal and systemic hemodynamic effects of ibopamine in patients with mild to moderate congestive heart failure.

To study the hemodynamic and renal effects of the orally (p. o.) active dopamine (DA) agonist ibopamine, we examined 10 patients with mild to moderate congestive heart failure (CHF), who were stable while treated with digoxin and diuretics. All patients were in New York Heart Association (NYHA) functional class II-III; their mean age was 63 years (range 51-79 years), and mean left ventricular ejection fraction (LVEF) was 28% (range 18-36%). The protocol consisted of a control study-day with measurements of renal characteristics including glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction (FF). One week later, systemic and renal hemodynamics were measured simultaneously before and after patients received one 100-mg tablet of ibopamine. Ibopamine caused a slight but significant increase in both ERPF (from 288 +/- 32 ml/min/1.73 m2 at baseline to 316 +/- 32 ml/min/1.73 m2 after ibopamine) and GFR (from 77 +/- 8 to 85 +/- 8 ml/min/1.73 m2; both p < 0.05); FF was not affected (mean value 0.26 +/- 0.02). Sodium excretion was not influenced by ibopamine, but diuresis increased significantly. Cardiac output (CO) increased significantly (from 4.0 +/- 0.4 L/min at baseline to a maximum of 5.0 L/min after ibopamine, p < 0.05), mainly due to decreased systemic vascular resistance (SVR). Heart rate (HR) and blood pressure (BP) were unchanged throughout the studies. The percentage of contribution of CO to renal blood flow (RBF) was not significantly affected by ibopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Interleukin-8 production by human mesothelial cells after direct stimulation with staphylococci.

Mesothelial cells (MC) are able to produce interleukin-8 (IL-8) after stimulation with IL-1 beta or tumor necrosis factor alpha. The aim of our study was to investigate whether MC are able to produce IL-8 after direct stimulation with clinically relevant bacteria. We observed a significant IL-8 response by the MC which were directly stimulated with viable staphylococci.

Cells, Cultured↗

Isolation and purification of large quantities of fresh human Kupffer cells, which are cytotoxic against colon carcinoma.

A new rapid method is described for the isolation and purification of functional active human Kupffer cells without the need of in situ perfusion techniques. Liver wedge biopsies (3 to 5 g), obtained after laparotomy, were incubated with pronase under continuous pH registration. Human Kupffer cells were subsequently separated from other nonparenchymal cells by Nycodenz gradient centrifugation and purified by counterflow centrifugal elutriation. Kupffer cells, 1.7 +/- 0.4 x 10(6) per gram liver, were isolated with a purity of 95% +/- 3%. Cell-mediated cytotoxicity of Kupffer cells was assayed against a human colon carcinoma cell line (SW948). Kupffer cell cytotoxicity was 42% +/- 9% (mean +/- SD) at an effector-to-target cell ratio of 10 and significantly increased to 73 +/- 17% (P < .05) after activation of Kupffer cells with interferon-gamma. In conclusion, a reliable and relatively simple method is provided to isolate and purify fresh human Kupffer cells in large yields, which show spontaneous as well as gamma-interferon-induced cytotoxicity against a human colon carcinoma cell line.

Carcinoma↗

Limited laparoscopic liver resection of benign tumors guided by laparoscopic ultrasonography: report of two cases.

Two cases of limited laparoscopic liver resection of benign tumors located in segment II and segment IV have been presented. The tumors were found during preoperative studies of biliary attacks and studied by means of ultrasonography and computed tomographic scan. During laparoscopy, the exact localization and surgical limits of the tumors were determined by visualization and laparoscopic ultrasonography. Dissection during laparoscopy was performed using the endoscopic cavitational ultrasonic surgical aspirator, achieving resection of the tumors with minimal blood loss.

Adenoma, Liver Cell↗

[Primary high-dose chemotherapy with hematopoietic growth factors followed by surgery and radiotherapy in stage III breast carcinoma; a Phase II study in 15 patients].

OBJECTIVE: To establish if the prognosis of a stage III breast carcinoma is improved by primary high-dose chemotherapy in combination with haemopoietic growth factors, followed by radical surgery and radiotherapy. DESIGN: Phase II study. SETTING: University Hospital Free University, Amsterdam. METHOD: Fifteen patients with a locally advanced breast carcinoma (stages IIIA or IIIB) were treated every three weeks with doxorubicin 90 mg/sq.m. and cyclophosphamide 1000 mg/sq.m., followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) 250 micrograms/sq.m. from day 2 up to and including day 12. After 4-6 of these courses the treatment in principle was continued with a modified radical mastectomy, followed by radiotherapy. Median duration of follow-up was 18 months. RESULTS: All tumours were reduced by over 50%. 10/15 Patients went into clinical complete remission; in 6/9 of these, pathological examination revealed only microscopical tumour rests, in the other three the rest diameter was < or = 1 cm. The haematological toxicity was mild. Grade III-IV bone marrow suppression was followed by rapid return to normal of the numbers of neutrophil granulocytes and thrombocytes under the influence of GM-CSF. The non-haematological toxicity manifested itself with nausea and vomiting, stomatitis and mild side effects attributable to GM-CSF. CONCLUSION: It appears justified in the treatment of locally advanced breast carcinoma to start with chemotherapy. Dose escalation of efficacious chemotherapeutics resulted in a large number of complete remissions.

Adult↗

Impact of intraoperative ultrasonography on treatment strategy for colorectal cancer.

The impact of intraoperative ultrasonography (IOUS) on treatment strategy was studied in 122 patients with primary colorectal cancer. All patients underwent preoperative liver imaging by ultrasonography and computed tomography (CT). After curative resection of the primary tumour patients were eligible for adjuvant chemotherapy. The findings on IOUS were assessed by ultrasonography 6 months after laparotomy. Of 34 patients with suspected liver metastases on ultrasonography or CT, the diagnosis was confirmed by IOUS in 21. In the remaining 13 patients the suspect lesions were shown to be benign. Of the 88 patients with normal preoperative imaging results, suspect lesions were detected in five; in four the lesion was found by IOUS only. One of these four also had an extrahepatic metastasis. At follow-up the diagnosis of metastasis proved to be wrong in two of the remaining three patients, so IOUS was helpful in only one patient. Surgical management was not markedly influenced by findings on IOUS in any patient. However, IOUS correctly changed the stage of the disease, and consequently postoperative treatment, in 14 patients (11 per cent). Two patients were erroneously excluded from the adjuvant protocol following an incorrect diagnosis based on IOUS.

Adult↗

Gamma probe-guided sentinel node biopsy to select patients with melanoma for lymphadenectomy.

A novel approach is described by which to identify the sentinel lymph node in patients with stage I melanoma. The technique involves a combination of intradermal patent blue V injection and gamma probe-assisted surgery. Eleven patients with previously resected cutaneous melanoma, clinical stage I (Breslow thickness 1.35-3.20 mm), underwent sentinel node biopsy. Before surgery lymphoscintigraphy was performed to evaluate the pathways of lymphatic drainage from the site of the previously resected melanoma. A handheld gamma probe was used to localize the sentinel node and to define the exact site of incision. At the same time, patent blue V (0.1-0.2 ml) was injected intracutaneously on either side of the scar to visualize the afferent lymphatic ducts and lymph nodes. By combining the use of the gamma probe and vital dye staining, the sentinel node could easily be localized and identified in all 11 patients. After removal of the sentinel node(s) no residual radioactivity could be traced. In four patients with micrometastases in the sentinel node standard lymph node dissection was performed, including excision of the biopsy site; in only one lymphadenectomy specimen were micrometastases found in two other lymph nodes.

Adult↗