Biomedical subjects

H C van der Linden

Publications and source records attributed to H C van der Linden.

12 recordsLinked to original sources

PubMed2002

Features of proliferation and in vitro drug resistance in central primitive neuro-ectodermal tumours.

The features of proliferation in brain tumours are related with clinical prognosis for several types of brain tumours, especially gliomas. For childhood central primitive neuro-ectodermal tumours (cPNET), including medulloblastoma, this relation has previously been unclear. The aim of this study is to investigate the relationship between proliferative features of cPNET and in vitro resistance for cytostatic drugs measured with the 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium-bromide (MTT) assay. Tumour material was obtained from 23 surgical specimens of cPNET. The expression of the proliferation markers Ki-67, proliferating cell nuclear antigen (PCNA) and cyclin D1 was determined with immunohistochemistry, while S-phase and DNA ploidy were analysed by flowcytometric analysis cell scan (FACS). The in vitro resistance for 10 cytostatic drugs was determined with the MTT assay. Drug resistance levels were available in 19 (83%) of the 23 samples with a complete profile of 10 cytostatic drugs tested in 14 samples. An excellent correlation in drug resistance scores was found between pharmacologically related drugs. The Ki-67 staining in 20 samples varied from 10 to 60% and from 30 to 100% for PCNA. Cyclin D1 staining was negative in 11 out of 18 samples. The S-phase in 16 samples ranged from 2 to 16%. Increased staining of Ki-67 was related with actinomycin D sensitivity (r -.603; P=0.022), while cells with a higher S-phase percentage were more resistant to ifosfamide (r.952; P<0.0001). In vitro drug resistance testing of central primitive neuro-ectodermal tumours (PNET) is feasible with the MTT assay. Ifosfamide resistance was related with increased Ki-67 and S-phase percentage of the tumour cells, while increased Ki-67 was also related with actinomycin D sensitivity. These findings suggest a cell cycle dependent activity of cytostatic drugs in vitro.

Antineoplastic Agents↗

PubMed2001

Histopathologic features of retinoblastoma and its relation with in vitro drug resistance measured by means of the MTT assay.

BACKGROUND: Retinoblastoma is frequently treated with chemotherapy to facilitate intraocular therapy, as well as to diminish or delay radiotherapy in invasive disease. It is also used more extensively in patients with dissemination to the central nervous system and/or the bone marrow. Once the disease has spread, the prognosis is poor. Radiotherapy is effective in ocular retinoblastoma, but is associated with facial deformation and a higher chance for second primary tumors in the irradiation field. These sequelae emphasize the need to determine more effective chemotherapy schedules and local treatment. The aim of this study is to investigate the relation between in vitro drug resistance for ten cytostatic drugs and histopathologic features in primary retinoblastoma. MATERIALS AND METHODS. Forty-four fresh samples of primary retinoblastoma were tested for in vitro drug resistance using the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. The histopathologic features for differentiation, invasion and intra-ocular extension, necrosis, mitosis, and apoptosis were scored. RESULTS: The differentiation of the tumors revealed 24 poorly differentiated, 14 intermediately differentiated, and 6 well differentiated tumors. Tumor infiltration showed 3 minimal and 3 massive choroideal invasions, as well as 21 prelaminary and 2 postlaminary optic nerve invasions. The tumor was unifocal in 16 eyes and multifocal in 28 eyes, with extensive retinal involvement in 10 eyes and tumor seeding in 21 eyes. The MTT assay was successful in 82% of the samples after enzymatic handling of the tumor cells was omitted. Undifferentiated tumors were more sensitive to carboplatin (p = 0.034) and doxorubicin (p = 0.025), thiotepa (p = 0.051) and ifosfamide (p = 0.075) in comparison to differentiated tumors. Type of retinal involvement, invasion, focality, and seeding did not show a relationship with drug resistance. Calcified tumors were more resistant to actinomycin D and ifosfamide and more sensitive to vincristine; conversely, apoptotic tumors were more sensitive to ifosfamide and more resistant to vincristine (p = 0.027). Necrotic tumors were more sensitive to actinomycin D (p = 0.004), and mitotic tumors were more sensitive to idarubicin (p = 0.026). In 90% of the tumors extreme drug resistance to cytarabin was present. CONCLUSIONS: In retinoblastoma many histopathologic features are related to in vitro drug resistance. Undifferentiated tumors are more sensitive to several cytostatic drugs. Calcification and apoptosis show an inverse relation with in vitro drug resistance to ifosfamide and vincristine. Extreme drug resistance to cytarabin is observed; this drug should not be used in retinoblastoma treatment.

Antineoplastic Agents↗

PubMed2001

HPV presence precedes abnormal cytology in women developing cervical cancer and signals false negative smears.

In a retrospective case-control study, we investigated high-risk HPV DNA presence by general primer GP5+/6+ PCR in the last normal cervical smear in the patient archives (i.e. baseline smear) of 57 women who later developed cervical cancer. Also, normal cervical smears of 114 age-matched control women were analysed. High-risk HPV DNA was detected in 37 of the 57 (65%) baseline smears of the case women, and 7 (6%) of 114 smears of the control women (OR 28, 95% Cl 11-72). The HPV positive subsequent smears and cervical cancer biopsies of the case women contained the same HPV type as was detected in the baseline smear. After cytological revision, the baseline smears of 48 case women (84%) were reclassified as abnormal, 33 (69%) of which scored high-risk HPV DNA positive. Ultimately, an undisputable normal baseline smear was found in only 10 case women. In 7 (70%) of them this smear was HPV positive, whereas only 7 (7%) of 104 revised, undisputable normal smears of control women were high-risk HPV positive (OR 32, 95% Cl 6.8-153). The results showed that (1) high-risk HPV presence precedes abnormal cytology in women who develop cervical cancer, and (2) high-risk HPV testing signals false-negative smears of women at risk of cervical cancer.

Adenocarcinoma↗

PubMed2000

Predictive value of sonographic examination to visualize retained placenta directly after birth at 16 to 28 weeks.

A prospective study was performed to assess the predictive value of an ultrasonographic examination directly after a spontaneous birth at 16 to 28 weeks' gestation to exclude the possibility of retained placental tissue. The aim of this procedure is to prevent routine curettage, which can induce Asherman's syndrome, uterine perforation, and anesthetic complications. Over a 2 year period the clinical course in 64 women, who had been delivered of their infants at 16 to 28 weeks' gestation, was followed through 6 weeks post partum. Sonographic examination was performed within 30 min after delivery of the placenta independent of macroscopic judgment of completeness of placenta. The examination was classified into three categories (with subsequent clinical interpretation): sharp lining of echogenic uterine wall with translucent cavity (uterine cavity containing fluid blood), sharp lining of the wall with echogenic area in cavity not continuous with the wall (uterine cavity with blood clot), and irregular lining with echogenic area continuous with the uterine wall and extending into the cavity (uterine cavity containing retained placental tissue). Women with sharp uterine lining without (n = 32) or with (n = 7) echogenicity in the cavity had no direct operative removal of placental tissue; 3 underwent curettage at a later stage (17, 18, and 34 days, respectively). A direct digital removal of placenta or curettage was performed on 25 women who revealed echogenicity continuous with the uterine wall. The 25 of 28 operatively obtained tissues were examined microscopically for trophoblasts. The sensitivity of the sonographic examination to find retained placental tissue was 85% (17 of 20) at 95% confidence intervals of 62 to 97%, the specificity was 88% (36 of 41) at 95% confidence intervals of 74 to 96%, and there were 25% (5 of 20) false positive judgments and 8% (3 of 39) false negative judgments. The positive predictive value of ultrasonography to find retained placenta of 68% (17 of 22) at 95% confidence interval of 55 to 92% combined with the negative predictive value of 92% (36 of 39) is sufficient to strongly suggest that curettage should not be performed routinely in these pregnancies at high risk for retained placental tissue.

Confidence Intervals↗

PubMed1999

Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study.

BACKGROUND: A relation has been established between infection with high-risk types of human papillomavirus and development of cervical cancer. We investigated a role for testing for human papillomavirus as part of cervical-cancer screening. METHODS: We monitored by cytology, colposcopy, and testing for high-risk human papillomavirus 353 women referred to gynaecologists with mild to moderate and severe dyskaryosis. The median follow-up time was 33 months. At the last visit we took biopsy samples. Our primary endpoint was clinical progression, defined as cervical intraepithelial neoplasia (CIN) 3, covering three or more cervical quadrants on colposcopy, or a cervical-smear result of suspected cervical cancer. FINDINGS: 33 women reached clinical progression. All had persistent infection with high-risk human papillomavirus. The cumulative 6-year incidence of clinical progression among these women was 40% (95% CI 21-59). In women with end histology CIN 3, 98 (95%) of 103 had persistent infection with high-risk human papillomavirus from baseline. Among women with mild to moderate dyskaryosis at baseline, a second test for human papillomavirus at 6 months predicted end histology CIN 3 better than a second cervical smear. INTERPRETATION: Persistent infection with high-risk human papillomavirus is necessary for development and maintenance of CIN 3. All women with severe dyskaryosis should be referred to gynaecologists, whereas women with mild to moderate dyskaryosis should be referred only after a second positive test for high-risk human papillomavirus at 6 months.

Adolescent↗

PubMed1998

Cytogenetics of a malignant ovarian germ-cell tumor.

Cytogenetic investigation of a malignant ovarian tumor diagnosed as a mixed germ-cell tumor, composed of extensive choriocarcinoma and foci of yolk-sac tumor, revealed a highly abnormal chromosomal pattern. We found a chromosome number in the hypertriploid/hypotetraploid range, and several clonal structural abnormalities, including 2 copies of an isochromosome 12p. We showed that the chromosomal pattern of this ovarian tumor is very similar to that of testicular germ-cell tumors. This finding, together with reported cytogenetic data of malignant ovarian germ-cell tumors, supports the hypothesis that ovarian and testicular germ-cell tumors are strongly related entities that may have a similar origin and pathogenetic pathway.

Adult↗

PubMed1997

First trimester development of human chorionic villous vascularization studied with CD34 immunohistochemistry.

Normal chorionic villous vascularization is essential for the undisturbed development of pregnancy. Defective vasculogenesis may play a role in pathological pregnancy. To assess pathological chorionic villous vascularization, normal vascularization has to be defined first. Few data are available on this topic. The aim of this study was therefore to investigate normal chorionic villous vascularization in ultrasound-dated first trimester pregnancies from week 5 menstrual age to week 12 (n = 41), using quantitative CD34 immunohistochemistry. Two important processes in chorionic villous vascularization were quantitatively illustrated: (i) maturation, reflected by an increase of the total number of luminized vessels as opposed to non-luminized haemangioblastic cords and (ii) margination, due to a decrease of villous stromal area and an increase of total villous vascular area. The percentage of villous stromal area occupied by vascular elements (area difference %) increased from 0.7% in week 5-2.5% in week 10. Therefore, the area of the villous stroma occupied by vascular elements increases and the vessels are situated closer to the trophoblastic layer suitable for fetal-maternal exchange. There was also a trend in increased number of peripheral vessels (2.0 in week 5 to 4.6 in week 10), supporting both developmental mechanisms. In conclusion, in exactly dated normal human first trimester pregnancies, development of the chorionic villous vascular system seems to be mostly characterized by maturation of luminized vessels from primitive haemangioblastic cords, and margination to a situation of peripherally located vessels.

Antigens, CD34↗

PubMed1996

Text processing by digital voice recognition.

OBJECTIVE: To evaluate digital voice recognition in free text mode. STUDY DESIGN: A standard medical text (182 words and punctuation marks) was dictated four times each by six people using a commercially available voice recognition system. RESULTS: The time used, including the time needed for making corrections, decreased from a median of 14.5 (6.3-18.8) minutes in the first session to a median of 6.7 (5.1-15.7) in the fourth session. the number of corrections necessary in the last session was a median of 20.5 (15-97)-i.e., 11% of the number of words in the text. All users described working with the system as highly strenuous. Dictating the same text with a dictaphone took median 1.4 (0.9-1.6) minutes and about five minutes of typing and correction time. CONCLUSION: Although the total time was about the same with the two methods, the time for the pathologist increased fourfold when using the voice recognition system. To obtain acceptable input speed, an appropriate template module is essential.

Signal Processing, Computer-Assisted↗

PubMed1993

Monoclonal antibody 4C7 recognizes an endothelial basement membrane component that is selectively expressed in capillaries of lymphoid follicles.

In order to define compartment-related structures within the extracellular matrix of human lymphoid organs, monoclonal antibodies (MAbs) were generated by immunizing mice with stromal fragments of human tonsils. One MAb (4C7) was selected which recognized an endothelial basal membrane component that is selectively expressed in capillaries of lymphoid follicles. The epitope was also present in follicles within chronically inflamed synovial membrane and in a hyperplastic thymus of a patient with myasthenia gravis. B-cell non-Hodgkin's lymphomas with a follicular growth pattern expressed the antigen in neoplastic follicles, whereas diffuse growing lymphomas lacked the antigen. The restricted distribution pattern suggests involvement of the 4C7-defined antigen in the organization of the follicular compartment within human lymphoid tissue.

Antibodies, Monoclonal↗

PubMed1991

Towards a quantitative grading of bladder tumors.

The histological inspection of tumor tissue for the purpose of reporting a tumor grade is a problem of significant clinical importance. The grading by a pathologist is only partly reproducible due to vaguely defined, subjective criteria. In this article we describe and evaluate a set of measurable features that quantitate the differences in tumor tissue. Different aspects of the reproducibility of the measurements under varying conditions of image selection, focus, and noise have been investigated. Three hundred thirty-three images were digitized from 111 bladder tissue sections (4 microns thick, Feulgen stained), using the ICAS microscope-camera platform. A segmentation routine was developed to segment the images into nuclei and background without any user interaction. Size, shape, optical density, and texture features were measured on and among the objects found by this segmentation routine using the image analysis package Acuity. The results of the measurements showed that there is a significant quantitative difference between grade 1 and grade 3 tumors. Grade 2 tumors can be described as "in between grade 1 and grade 3" and falling somewhere on an increasing scale between grades 1 and 3. Grade 2 tumors do not seem to represent a statistically distinct population. The procedure described here is shown to be quite reproducible in the presence of noise, reasonably reproducible in the event of a modest amount of defocusing (with grade 3 tumors exhibiting the most sensitivity), and less reproducible in the context of which fields-of-view are chosen for analysis.

Epithelium↗

PubMed1989

Human papillomavirus detection in paraffin-embedded cervical carcinomas and metastases of the carcinomas by the polymerase chain reaction.

The polymerase chain reaction (PCR) is used for human papillomavirus (HPV) detection in paraffin-embedded tissue. The specificity of the reaction is unaffected by the method of fixation used before embedding into paraffin. Five HPV 16, 18, 31, and 33 DNA in situ hybridization (DISH)-negative cervical carcinomas were subjected to the PCR. In two patients, HPV 16 DNA could be detected in the cervical squamous cell carcinomas and also in their lymph node metastases. One patient with an adeno-carcinoma of the cervix was found positive for HPV-18. A lymph node of this patient was HPV 18 positive as well. In the tumors of the remaining two patients, no HPV 16, 18, or 33 DNA was detected by the PCR. Both negative patients had cervical squamous cell carcinomas. One had a bladder metastasis, whereas the other had a lymph node metastasis and an additional distant metastasis in the lung. HPV DNA positivity in cervical carcinomas correlated with HPV prevalence in the metastases. This relationship can be of use for diagnostic purposes in the pathologic analysis of metastases.

Blotting, Southern↗

PubMed1986

Morphometry and breast cancer. II. Characterisation of breast cancer cells with high malignant potential in patients with spread to lymph nodes: preliminary results.

The prognostic value of clinical, quantitative, and qualitative microscopical features of both the primary tumour and also of the affected lymph nodes were investigated in 71 patients with breast cancer with spread to lymph nodes (T X N + M0). Age, tumour size, and localisation of the tumour comprised the clinical features; morphometry included assessment of the cellularity index, the mitotic activity index, and seven nuclear indices; the qualitative features investigated were histological type and grade, nuclear grade, oestrogen receptor content, number of lymph nodes affected, capsule infiltration of the nodes, presence of metastatic deposits in the efferent lymph vessels, percentage area of lymph node occupied by tumour. Immunohistochemistry was performed to show the presence of carcinoembryonic antigen and peanut agglutinin. All the patients had a minimum follow up of 24 months (maximum 48 months, mean 36 months). Analysis of the results showed that the combined results of morphometry (of the primary tumour and the axillary lymph node metastatic deposits) yielded more information than analysis of axillary lymph node state, or morphometry of the primary tumour, or the lymph node metastases alone. Patients with a nuclear axes ratio of greater than 1.41 in the primary tumour and greater than 1.36 in the lymph node metastatic deposits were less likely to develop distant metastases than patients with values below any of these thresholds (recurrence rates 5.2% and 46%, respectively). Thus the preliminary results of this prospective study indicate that morphometry provides important prognostic information in patients with breast cancer that has spread to lymph nodes.

Adult↗