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Biomedical subjects

H Doornewaard

Publications and source records attributed to H Doornewaard.

At least 19 recordsLinked to original sources

[Submucosal lipoma of the colon: abdominal cramps with rectal bleeding and weight loss].

An 81-year-old woman had abdominal cramps, rectal bleeding since 2 weeks and weight loss. Colonoscopy showed an ulcerating tumour of about 4 cm in the transverse colon. Pathological examination of biopsies taken during colonoscopy indicated moderately active chronic colitis. Based on the colonoscopy findings, the tumour appeared to be malignant and laparotomy was performed and the transverse colon was resected. Pathological examination of the resected lesion revealed a submucosal lipoma. The patient recovered fully. Lipomas account for 4% of benign gastrointestinal tumours and 90% of lipomas are submucosal. Their presentation is often similar to malignant tumours. The naked fat sign after biopsy and the elasticity of the lesion are typical features encountered during colonoscopy. Given the high fat content of these lesions, they are easily discernible with CT and MRI. Lipomas with a diameter < 2 cm can be safely removed endoscopically. Larger lesions should be removed by segment resection.

Abdominal Pain↗

Neural network-based screening (NNS) in cervical cytology: no need for the light microscope?

Neural network-based screening (NNS) of cervical smears can be performed as a so-called "hybrid screening method," in which parts of the cases are additionally studied by light microscope, and it can also be used as "pure" NNS, in which the cytological diagnosis is based only on the digital images, generated by the NNS system. A random enriched sample of 985 cases, in a previous study diagnosed by hybrid NNS, was drawn to be screened by pure NNS. This study population comprised 192 women with (pre)neoplasia of the cervix, and 793 negative cases. With pure NNS, more cases were recognized as severely abnormal; with hybrid NNS, more cases were cytologically diagnosed as low-grade. For a threshold value > or = HSIL (high-grade squamous intraepithelial lesions), the areas under the receiver operating characteristic (ROC) curves (AUC) were 81% (95% CI, 75-88%) for pure NNS vs. 78% (95% CI, 75-81%) for hybrid NNS. For low-grade squamous intraepithelial lesions (LSIL), the AUC was significantly higher for hybrid NNS (81%; 95% CI, 77-85%) than for pure NNS (75%; 95% CI, 70-80%). Pure NNS provides optimized prediction of HSIL cases or negative outcome. For the detection of LSIL, light microscopy has additional value.

Cervix Uteri↗

Observer variation in cytologic grading for cervical dysplasia of Papanicolaou smears with the PAPNET testing system.

BACKGROUND: To assess the interobserver and intraobserver variation of Papanicolaou (Pap) smear screening with the computer-assisted (neural network based) PAPNET Testing System in diagnosing cervical smear abnormalities, results of agreement were compared with the interobserver and intraobserver variation of conventional smear analysis. METHODS: Cervical smears obtained from women in 1996 were reevaluated both by conventional light microscopy and with use of the PAPNET Testing System by the same four investigators, and results were compared with the original screening diagnoses obtained by both methods. RESULTS: The interobserver results for epithelial abnormalities (the degree of agreement between the cytologists), characterized by weighted kappa statistics, were 0.71 (95% CI: 0. 68-0.73) for PAPNET screening and 0.69 (95% CI: 0.66-0.72) for conventional screening. No significant differences were found among the individual results obtained by the four cytotechnologists (intraobserver variation) with conventional screening versus PAPNET reviewing. CONCLUSIONS: Pap smear grading with the PAPNET Testing System has interobserver and intraobserver variation similar to that of conventional screening of Pap smears in routine use. Cancer (Cancer Cytopathol)

Diagnosis, Differential↗

Effects of ursodeoxycholic acid therapy on in vitro gallbladder contractility in patients with cholesterol gallstones.

During treatment with ursodeoxycholic acid (UDCA), the fasting gallbladder volume increases by a yet unknown mechanism. The present study tests whether in vitro human gallbladder contractility in response to acetylcholine and cholecystokinin is affected by UDCA therapy. Gallbladder tissue was obtained from 15 patients treated with UDCA (10 mg/kg/day) during three weeks prior to surgery, and from 15 comparable patients not treated. Data were correlated with in vivo contractility, bile composition, and gallbladder wall inflammation. The inflammation score was lower in the treated patient group. UDCA treatment enhanced gallbladder contractility in vitro: Dose-response curves for acetylcholine and cholecystokinin were both shifted to the left, and the maximal contractile stress generated in response to cholecystokinin was higher in the treated group, whereas the maximal acetylcholine-induced stress was not increased. Maximal cholecystokinin-induced stress correlated positively with fasting gallbladder volume and negatively with the biliary cholesterol saturation index, but not with bile salt hydrophobicity or gallbladder wall inflammation score. In conclusion, UDCA treatment improves in vitro gallbladder contractility, possibly related to a reduced biliary cholesterol saturation. Increased fasting gallbladder volumes during UDCA treatment thus do not appear to result from decreased gallbladder muscle contractile strength.

Acetylcholine↗

Determination of actin content in gallbladder tissue and its relevance to normalization of tensiometry data.

OBJECTIVES: To compare the common procedure in tensiometry of normalization of the force (in N) produced by a gallbladder tissue strip to units of stress, with normalization of force to the strip content of contractile protein. DESIGN: A comparison was made in both healthy and in diseased gallbladder tissue strips between two normalization procedures involving anatomical parameters. The contractile response expressed in terms of tissue stress (in N/m2), which entails a normalization to the strip cross-sectional area, was set against normalization to the tissue content of contractile protein (in N/mg actin/g strip wet weight). METHOD: Dose-response curves for acetylcholine (ACh) (10(-8) to 10(-3) M) and sulphated cholecystokinin octapeptide (CCK) (10(-12) to 10(-6) M) were assessed in healthy guinea pig (n = 8) and in diseased human gallbladder tissue strips (n = 28). Assuming a tissue density of 1.05 g/cm3, the strip cross-sectional area was calculated from its weight and length. Actin content in homogenized strips was determined by polyacrylamide gel electrophoresis followed by densitometry. RESULTS: Actin content in human tissue was 19.06 +/- 1.42 mg/g strip wet weight, and 12.84 +/- 0.76 mg/g strip wet weight in guinea pig tissue. No correlation was found between strip cross-sectional area and actin content. In the diseased human tissue, no correlation was found between the inflammation score and either strip cross-sectional area or strip actin content. Maximal force (in mN) exerted in response to either ACh or CCK correlated much more closely in healthy guinea pig gallbladder (r = 0.97) than in diseased human tissue (r = 0.59). Normalization of maximal force to strip cross-sectional area (i.e. to stress) showed considerable more variation (% coefficient of variance) than the normalization to strip actin content in healthy guinea pig tissue, although both strip cross-sectional area and actin content per se showed little variation. Normalization to either parameter did not result in an improved correlation or a decreased variation in the case of diseased human gallbladder tissue. CONCLUSION: Normalization of muscle strip force in diseased tissue is questionable, as the assumptions made for healthy tissue are not valid.

Acetylcholine↗

The diagnostic value of computer-assisted primary cervical smear screening: a longitudinal cohort study.

OBJECTIVES: To assess computer-assisted (neural network based) cervical smear screening as a primary tool for the early detection of cervical dysplasia. DESIGN: Longitudinal cohort study. SETTING: Cytology laboratory reviewing cervical smears taken by general practitioners in a mass screening program in the Netherlands. SUBJECTS: 846 women who developed (pre-)neoplasia of the cervix in the seven years after the baseline smear, and 5217 controls. INTERVENTIONS: Cervical smears were evaluated both by conventional light microscopy and with use of the PAPNET Testing System by the same cytotechnologists. MAIN OUTCOME MEASURES: Seven year histological and cytological follow-up results were obtained for all women from a nation-wide pathology database. RESULTS: Conventional screening diagnosed dysplasia or carcinoma in the baseline smears of 458 (54.1%) of the 846 women who were diagnosed with (pre-)neoplasia during follow-up, whereas computer-assisted PAPNET analysis detected such lesions in 462 (54.6%) of these women. In the control population of 5217 (86.0%) women, in whom follow-up revealed no cervical dysplasia, conventional screening gave false positive results in 210 (4.0%) and computer-assisted PAPNET analysis gave false positive results in 207 (4.0%) smears. The areas under the receiver operation curves (AUC) were 80% (95% confidence interval, 78 to 82%) and 79% (95% confidence interval, 77 to 81%) for conventional and PAPNET-assisted screening, respectively. CONCLUSIONS: The PAPNET Testing System has similar diagnostic value as the conventional screening of Pap smears when used for primary screening.

Female↗

Evaluation of PAPNET-assisted cervical rescreening.

We have compared the results of targeted manual rescreening of 1211 randomly selected smears with the results of PAPNET-assisted rescreening of 1613 cervical smears, containing at least 6.3% low-grade squamous intraepithelial lesion (SIL). PAPNET diagnosis and the targeted rescreening diagnosis were compared with the initial report, issued on the corresponding smear. Reproducibility scores for inadequacy, presence of endocervical and endometrial cells, specific infections and squamous cell abnormalities were determined. The reproducibility scores for the diagnosis of inadequate smears and specific infections were lower with the PAPNET-assisted rescreening. The detection of squamous cell abnormalities was excellent for both methods (> 0.95), with a higher detection rate for false-negative smears with the PAPNET testing system.

Diagnosis, Computer-Assisted↗

Focal liver lesions: characterization with triphasic spiral CT.

PURPOSE: To assess whether triphasic spiral CT enables characterization of a wide range of focal liver lesions. MATERIALS AND METHODS: One hundred five patients with suspected focal liver disease underwent triphasic liver CT. After injection of contrast material, the liver was scanned in arterial (scanning delay, 22-27 seconds), portal (scanning delay, 49-73 seconds), and equilibrium (scanning delay, 8-10 minutes) phases. Enhancement of each lesion in each phase was evaluated, and the lesions were tabulated according to one of 11 enhancement patterns. RESULTS: In 94 patients, 375 liver lesions were detected. The nature of the lesion was confirmed in 326 lesions (87%). Six of 11 enhancement patterns were always due to benign disease and caused by areas with hyper- or hypoperfusion, hemangiomas, cysts, focal nodular hyperplasias, or benign but nonspecified lesions. Two of 11 patterns were always due to malignant disease, and one pattern was due to malignant disease in 38 (97%) of 39 patients with known malignancy elsewhere or with chronic liver disease. The other two patterns were seen in metastases and partly fibrosed hemangiomas. CONCLUSION: Triphasic liver CT enables characterization of a wide range of focal liver lesions, including the benign liver lesions that occur most frequently.

Adult↗

The effects of the 3-hydroxy, 3-methylglutaryl coenzyme A reductase inhibitor pravastatin on bile composition and nucleation of cholesterol crystals in cholesterol gallstone disease.

3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce biliary cholesterol saturation index (CSI) in duodenal bile in hypercholesterolemic patients and might be useful for gallstone dissolution. However, preliminary data suggest that these drugs are not effective in this respect. We therefore studied 33 patients with radiolucent gallstones in an opacifying gallbladder who were scheduled for elective cholecystectomy. Patients were treated with 40 mg pravastatin day-1 or placebo during the 3 weeks before surgery. Six patients could not be evaluated. Baseline characteristics (age, sex, body mass index, serum cholesterol, and the solitary/multiple gallstone ratio) were similar in both groups. Serum cholesterol fell by 39% in the pravastatin group (P < .001) and remained unchanged in the placebo group. Biliary cholesterol (9.5 +/- 1.3 vs. 14.3 +/- 1.5 mmol/L, P = .026), and phospholipid concentrations (24.8 +/- 3.9 vs. 36.7 +/- 3.9 mmol/L, P = .043) were lower in the pravastatin group. Although bile salt concentrations were lower in the pravastatin group (114 +/- 21 vs. 152 +/- 15 mmol/L), this difference was not significant. CSI was not different between both groups (142 +/- 27% [pravastatin] vs. 113 +/- 6% [placebo], P = NS). Cholesterol crystals were present in fresh bile in 7 of 13 patients in the pravastatin group and in 11 of 14 controls (P = NS). Nucleation time was comparable between the 2 groups (13 +/- 3 vs. 9 +/- 3 days, P = NS). Bile salt species and molecular species of phospholipids determined with high-performance liquid chromatography did not differ either between both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗

Reduction of donor-specific cytotoxic T lymphocyte precursors in peripheral blood of allografted heart recipients.

Tolerance to allografted hearts in human recipients has been observed both in clinical situations and in in vitro experiments. To elucidate whether a quantitative change of alloreactive CTL is one of the mechanisms accounting for this graft tolerance, CTL precursor (CTLp) frequencies in the peripheral blood of 10 heart recipients were measured against spleen cells from donors and HLA nonidentical third-party persons. In this longitudinal follow-up study, we showed that the rejection reaction(s) in the grafted heart correlated with CTLp frequencies in samples taken before transplantation against the donor spleen cells, but not with the CTLp frequencies against the spleen cells from the third-party persons. The CTLp frequencies against the spleen cells from donors decreased 4-6 months after transplantation, and remained at a low level afterward. However, the CTLp frequencies against spleen cells from third-party persons in blood samples obtained 1 year after transplantation were not significantly different from those before transplantation. Therefore, we conclude that donor-reactive CTLs are important in rejecting allografted heart. The decrease in donor-specific CTLp after transplantation could explain the donor-specific tolerance. The decrease may be due to homing of the specific CTLp to the graft, or by clonal deletion of the donor-reactive CTL caused by chronic alloantigen stimulation in the presence of immunosuppressive therapies.

Blood Cells↗

[National results of cervix cytology diagnosis in 1992; efficacy of screening could be improved].

OBJECTIVE: To analyse all cervical smears performed in 1992 to determine the number of tests per age category and to evaluate the efficacy of the test. DESIGN: Descriptive, retrospective. SETTING: The Netherlands. METHOD: Of every cervix smear registered in the Pathological Anatomical National Automised Archives (PALGA) the quality, signs of inflammation, squamous or columnar epithelial abnormalities and other abnormalities were determined (KOPAC code). RESULTS: In 1992, 784,046 cervix smears were registered, of which 755,844 were KOPAC-coded. Half of the smears came from women younger than 40 years. There was a high frequency of squamous cell abnormalities (II% Pap 2, 2.5% Pap 3a, 0.5% Pap 3b or worse). An accelerated second smear (after 3 months or 1 year) was performed in 14% of the women; 9% underwent > or = 2 cervical smears within 1 year. CONCLUSION: Related to the frequency of newly diagnosed cervix cancer (700 per year), the efficacy of cytology could be improved by limiting the number of smears and strictly applying the assessment criteria to diminish the number of accelerated second smears. Furthermore, second smears should be subject to strict management, determined by evaluation studies.

Adolescent↗

Posttransplant T-cell lymphoma. Report of three cases and a review of the literature.

BACKGROUND: Although 14% of the malignant lymphomas after organ transplantation are reported to be T-cell lymphomas, only a few cases are described in the literature. METHODS: The authors presented three new cases. They summarized the clinical data and analyzed histologic and immunochemical findings. The presence of Epstein-Barr virus (EBV) and human T-cell lymphoma type 1 (HTLV-1) were investigated. T-cell receptor (TCR) rearrangement was analyzed by Southern blot technique in two cases. RESULTS: Two of the three lymphomas developed after renal transplantation. One was a T-cell lymphoma of pleomorphic medium-sized cell type and the other was a T-cell lymphoblastic lymphoma; the third T-cell lymphoma was an anaplastic large cell (Ki-1 positive) type that developed after heart transplantation. No association was established with EBV or HTLV-1. A monoclonal TCR rearrangement was found in the two cases that were analyzed. A literature search revealed 22 other cases. Nineteen of the 22 reported cases were peripheral T-cell lymphomas. Almost all lymphomas presented in extra-nodal sites. The time between diagnosis and organ transplantation seemed to be influenced by the type of immunosuppressive therapy. In five cases, EBV was detected in the tumor cells. A monoclonal T-cell receptor rearrangement was found in eight cases and a polyclonal proliferation in one case. Response to therapy was variable, but often poor. CONCLUSIONS: The etiology of posttransplant T-cell lymphomas remains unclear. Similarities with posttransplant B-cell proliferations are the predominant extranodal presentation and the finding that the time of occurrence is influenced by the type of immunosuppression. In contrast with posttransplant B-cell proliferations, only a minority of the cases are associated with EBV. Most tumors appear to be monoclonal. Prognosis is generally poor, but tumor presentation with localized disease might have a somewhat better prognosis.

Adolescent↗

[The significance of endometrial cells in the cervical smear].

Presence of atypical endometrial cells in a cervical smear is quite unusual; but if they are found the woman needs extra attention because of the risk of adenocarcinoma of the uterus. Postmenopausal women sometimes also have endometrial cells without atypia in the cervical smear, as a sign of endometrial pathology. We conducted a retrospective follow-up study of these women. From 1978 to 1989, 52 smears from a total of about 50,000 postmenopausal women were classified as Pap IIIA, due to the presence of normal endometrial cells. Histological follow-up was performed in 25 cases and 3 times an adenocarcinoma of the endometrium was diagnosed (6%). The smears from 142 women (pre- and postmenopausal) contained atypical endometrial cells and therefore were classified as Pap IIIA or higher. Histological follow-up was performed in 104 cases. In 48% (n = 68) an adenocarcinoma was diagnosed. In 75% of these cases (n = 51) the atypical cells were graded as severe or worse (> or = Pap IIIB). Cervical smears are not taken to detect pathology of the endometrium, but whenever atypical cells are found in the smear there is a strong indication for further (gynaecological) examination.

Adenocarcinoma↗

[Cervix smears with mild atypia classified as Pap-class IIIA: results of a changed policy].

To evaluate the changed policy regarding cervical smears with mild atypia in the Netherlands (before 1988 classified as Pap II, thereafter as Pap IIIA), an descriptive study was carried out in the laboratory of gynaecological cytology Cyt-U-Universitair (University of Utrecht). All women who in 1988 had a first smear with mild atypia were included. After a follow-up period of 2 years the final diagnosis was noted. The results of the follow-up of cervical smears with mild atypia were compared with the follow-up results of moderate atypia. A selection was made of 477 women. In 55% of the cases no dysplasia was found during the 2 years of follow-up. In 12% of the cases severe dysplasia, carcinoma in situ or carcinoma was found. Compared with the smears with moderate atypia the dysplasia in the follow-up of mild atypia led to fewer cases of proven dysplasia. In addition the dysplasia in these cases was of a lower grade. The group of women referred to the gynaecologist after the smear with mild atypia was remarkably large (30%). As the results show, the policy of careful follow-up of women with mild atypia in the cervical smear has been a good one. It implies classifying mild atypia as Pap IIIA. As many women (55%) do not display cervical dysplasia within a 2 year follow-up period, the policy of making a repeat smear before referring appears justified.

Adult↗

Contribution of the cytobrush to determining cellular composition of cervical smears.

A study was made of the contribution of the cytobrush to determining the composition of the cervical smear. From a population of women screened in The Netherlands in 1987, 733 women were selected whose smears for the second time in a row lacked endocervical cells. Note was made of method of contraception, age of the woman, and day of the menstrual cycle. A control group was formed of women whose smears contained endocervical cells. Highly significant differences were found in the results between the two groups. Two new samples were collected, one made with the modified wooden Ayre spatula, the other with the cytobrush from the research group. The number of smears containing endocervical cells increased from 44% (by spatula alone) to 79% (spatula plus cytobrush). The cytobrush alone produced a high percentage of unsatisfactory smears (17.5%) due to a low content of squamous epithelial cells. No differences could be observed in the rate of cellular atypia because of the small number of cases.

Cell Count↗