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F B Thunnissen

Publications and source records attributed to F B Thunnissen.

At least 19 recordsLinked to original sources
PubMed2006

EU-USA pathology panel for uniform diagnosis in randomised controlled trials for HRCT screening in lung cancer.

Randomised controlled trials for lung cancer screening using high-resolution computed tomography are now underway. In order to allow effective future comparison of the different trials, as well as strengthening conclusions based upon the analysis of larger data sets, uniformity and consistency of pathology diagnosis are essential. The aim of the present study was to determine the effectiveness of the learning process in this difficult area of diagnostic pathology. Eight pathologists received two CD-ROMs, each with digital images of 30 cases. After diagnosing the first series, selected background reading was provided. Kappa (kappa) scores were calculated for each pathologist and category, and were compared to the consensus score. The readings of the first series showed a moderate agreement kappa score: mean+/-sd for category numbers 8 (all eight categories) and 2 were 0.53+/-0.05 and 0.65+/-0.04, respectively. The kappa 2 score distinguished between categories denoting benign and malignant lesions. The second series resulted in a good agreement kappa score: 0.65+/-0.06 for category number 8 and 0.81+/-0.02 for category number 2. In conclusion, this study demonstrates that screen-detected cases pose particular problems for pathologists and that a trained pathology panel serving randomised controlled trials is likely to lead to more consistent and accurate tissue diagnosis.

Adenocarcinoma↗
PubMed2001

NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response.

A wealth of evidence supports increased NO (NO.) in asthma, but its roles are unknown. To investigate how NO participates in inflammatory airway events in asthma, we measured NO. and NO. chemical reaction products [nitrite, nitrate, S-nitrosothiols (SNO), and nitrotyrosine] before, immediately and 48 h after bronchoscopic antigen (Ag) challenge of the peripheral airways in atopic asthmatic individuals and nonatopic healthy controls. Strikingly, NO(3)(-) was the only NO. derivative to increase during the immediate Ag-induced asthmatic response and continued to increase over 2-fold at 48 h after Ag challenge in contrast to controls [P < 0.05]. NO(2)(-) was not affected by Ag challenge at 10 min or 48 h after Ag challenge. Although SNO was not detectable in asthmatic airways at baseline or immediately after Ag, SNO increased during the late response to levels found in healthy controls. A model of NO. dynamics derived from the current findings predicts that NO. may have harmful effects through formation of peroxynitrite, but also subserves an antioxidant role by consuming reactive oxygen species during the immediate asthmatic response, whereas nitrosylation during the late asthmatic response generates SNO, safe reservoirs for removal of toxic NO. derivatives.

Adult↗
PubMed2001

Mitotic counting in surgical pathology: sampling bias, heterogeneity and statistical uncertainty.

Mitotic counting in surgical pathology: sampling bias, heterogeneity and statistical uncertainty Although several articles on the methodological aspects of mitotic counting have been published, the effects of macroscopic sampling and tumour heterogeneity have not been discussed in any detail. In this review the essential elements for a standardized mitotic counting protocol are described, including microscopic calibration, specific morphological criteria, macroscopic selection, counting procedure, effect of biological variation, threshold, and the setting of an area of uncertainty ('grey area'). We propose that the use of a standard area for mitotic quantification and of a grey area in mitotic counting protocols will facilitate the application of mitotic counting in diagnostic and prognostic pathology.

Data Interpretation, Statistical↗
PubMed2001

Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells.

A critical first-line antioxidant defense on the airway epithelial surface against reactive oxygen and nitrogen species (ROS and RNS) is extracellular glutathione peroxidase (eGPx). Little is known about the regulation of eGPx or its role in ROS-mediated lung diseases such as asthma. Here we show that eGPx is increased in the asthmatic airway in comparison to healthy controls. Higher levels of eGPx mRNA in asthmatic airway epithelium verified bronchial epithelial cells as the source for the increased eGPx. The eGPx mRNA in bronchial epithelial cells in vitro increased eightfold after exposure to ROS and glutathione, an essential cofactor for eGPx activity. Alterations in intracellular and extracellular oxidized and reduced glutathione were temporally associated with eGPx induction, further supporting redox mechanisms in gene expression. Overexpression of superoxide dismutase, but not catalase, inhibited induction and identified superoxide as a key intermediary. The eGPx mRNA half-life was not affected by ROS, suggesting a transcriptional mechanism for eGPx regulation. Fusion genes of deletion fragments of the eGPx gene 5' flanking region driving a reporter gene conclusively identified the ROS-responsive region, which contained the consensus DNA binding site for the redox-regulated transcription factor, activator protein 1.

Asthma↗
PubMed2000

[Summary of the guideline 'Sentinel node biopsy in breast cancer.' Dutch Work Group 'Sentinel Node Biopsy for Breast Cancer'].

The team Sentinel Node Biopsy Breast Cancer issued guidelines for the performance of the sentinel node procedure. The team took into account the problems resulting from the introduction of the technique. The eligible group consists mainly of women with demonstrated breast cancer with a diameter of < or = 2 cm without palpable axillary nodes. Contraindications include presence of more than one tumour, pathological nodes in the ipsilateral axilla and previous treatment of breast or axilla. After injection of a radioactive substance, the sentinel node is detected during the operation using a gamma probe. The tracer is injected 2 to 24 hours before the operation in or near the tumour. Shortly before the incision, patent blue is injected as well, improving the detectability of the sentinel node. One or several sentinel nodes are examined histologically. The pathology report meets minimal requirements. In the planning and introduction of the technique in a hospital a locally responsible radiation expert should be involved. The procedure should be performed a number of times and evaluated with reference to a histopathological result before it is decided to draw clinical conclusions from the procedure. For the necessary evaluations of the procedure central registration is an absolute condition.

Breast Neoplasms↗
PubMed2000

Pulmonary atypical carcinoid: predictors of survival in 106 cases.

Pulmonary neuroendocrine tumors (NE) include a spectrum of tumors from typical carcinoid (TC) to atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCLC). Little is known about prognostic predictors for AC because of its rarity. Survival analysis was performed on 106 ACs with clinical follow-up from the AFIP and the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). The tumors fulfilled the 1999 WHO/IASLC criteria for AC of a NE tumor with a mitotic rate of 2 to 10 per 2 mm(2) of viable tumor or coagulative necrosis. Multiple clinical and histologic features were analyzed by Kaplan-Meier and Cox regression analysis. Of the clinical features, higher stage (P = .003) and a tumor size of 3.5 cm or greater (P = .003) were associated with a worse prognosis. Features that were histologically unfavorable by univariate analysis were mitotic rate (P =.002), pleomorphism (P = .018), and aerogenous spread (P =.007). Histologically favorable features by univariate analysis were the presence of palisading (P = .008), papillary (P = .039), pseudoglandular (P =.026), and rosette (P = .022) patterns. Female gender showed a trend toward a poorer prognosis (P =.085) and was included in the multivariate model. Multivariate analysis stratified for stage showed mitoses (P<.001), a tumor size of 3.5 cm or greater (P =.017), and female gender (P =.012) to be the only negative independent predictors of prognosis and the presence of rosettes (P = .016) to be the only independent positive predictor. We further divided the AC into subgroups of low (2 to 5 mitoses/2 mm(2)) and high (6 to 10 mitoses/2 mm(2)) mitotic rate and compared the survival with TC and with LCNEC. Within the category of AC, the patients with a higher mitotic rate had a significantly worse survival than those with a lower mitotic rate (P<.001) stratified for stage. Five- and 10-year survival rates for AC (61% and 35%, respectively) stratified for stage were significantly worse than for TC and better than that for LCNEC and SCLC. Chemotherapy or radiation therapy was given in 12 of 52 and 14 of 52 cases, respectively, but the data were insufficient to evaluate tumor response. We conclude that AC is an aggressive neuroendocrine neoplasm with survival intermediate between TC and LCNEC and SCLC. Higher mitotic rate, tumor size of 3.5 cm or greater, female gender, and presence of rosettes are the only independent predictors of survival. Surgical resection remains the treatment of choice, and the role of chemotherapy and radiation therapy remains to be proven.

Adult↗
PubMed2000

Solitary intestinal fibromatosis as a cause of bile vomiting in a neonate.

The authors describe a 3-day-old newborn admitted with signs of intestinal obstruction caused by solitary intestinal fibromatosis (SIF). This is a very rare lesion, which has an excellent prognosis. The differential diagnosis of bilious vomiting in a neonate caused by other than tumorous processes in the neonatal intestine is extensive. Probably this kind of lesion is more frequent in the neonatal period than thought until now but underdiagnosed because of the difficulty of diagnosis. Therapy of choice is wide local excision, and prognosis is excellent.

Bile↗
PubMed2000

New protocol for DNA extraction of stool.

Present methods for DNA isolation of stool have various limitations such as the amount of stool used, the requirement of lavage fluids or the use of fresh stool. In this paper, a new method is described for the isolation of human nucleic acids from stool, which is independent from the moment of collection. Fecal samples as dry as possible were collected from 75 patients; two grams of stool were mixed with a lysis buffer containing phenol. DNA yields of crude stool were variable and ranged from 9-1686 micrograms/g of feces. With dot blots in 9 of the 75 cases, the human DNA was identified and ranged from 0.06%-46%. In the remaining 66 cases, human genomic DNA was detected by nested PCR, using human K-ras gene amplification as an example. Amplification products were confirmed for human K-ras with the exonuclease-amplification coupled capture technique (EXACCT). In conclusion, the developed DNA isolation method can be used for the study of large numbers of stool samples, is independent of the age or method of stool collection and is suitable for large-scale screening studies.

Base Sequence↗
PubMed2000

Conventional gas ventilation, liquid-assisted high-frequency oscillatory ventilation, and tidal liquid ventilation in surfactant-treated preterm lambs.

This study was designed to compare the efficacy and potential protective or injurious effects of tidal liquid ventilation (TLV), liquid-assisted high-frequency oscillatory ventilation (LA-HFOV), and high PEEP conventional mechanical ventilation (CMV) in neonatal respiratory distress syndrome. Preterm lambs (124-126 days gestation), prophylactically treated with natural surfactant, were allocated to one of the treatment modalities or to an untreated fetal control group (F), euthanised after tracheal ligation. LA-HFOV animals received an intratracheal loading dose of 5 mL x kg(-1) followed by a continuous intrapulmonary instillation of 12 mL x kg(-1);h(-1) FC-75 perfluorocarbon liquid. The ventilation strategies aimed at keeping clinically appropriate arterial blood gases for a study period of 5 hours. A histological lung injury score was calculated and semiquantitative morphometry was performed on lung tissue fixed by vascular perfusion. The alveolar-arterial pressure difference for O2 was significantly lower throughout the study in TLV compared to CMV lambs; at 1, 2, and 5 hours, oxygenation was better in TLV when compared to LA-HFOV. Total lung injury scores in TLV lambs were significantly lower than in either CMV or LA-HFOV animals, but higher when compared to F. CMV and LA-HFOV induced an excess of collapsed and overdistended alveoli, whereas in TLV alveolar expansion was normally distributed around predominantly normal alveoli. CMV and LA-HFOV, but not TLV, were associated with an excess of dilated airways. Thus, in the ovine neonatal RDS model, TLV compared favourably to either gas ventilation strategy by its more uniform ventilation, reduced lung injury, and improved gas exchange.

Analysis of Variance↗
PubMed1999

Clinical value of DNA image cytometry in effusions with atypia.

Malignant cells in serosal effusions provide essential information about the extent of malignant disease. The main aim of this study was to examine the additional diagnostic value of DNA image cytometry for cases with uncertainty in the cytological diagnosis. In addition, the feasibility of automated nuclei detection was investigated. Out of 457 cases, 33 samples in 32 patients were diagnosed with "atypia" (probably benign) and 21 as "suspicious for malignancy." DNA image cytometry was performed on these 54 cases and on an additional group of 14 cytologically malignant cases. The results show that automatic classification is useful for separation of control cells, i.e., lymphocytes and neutrophilic granulocytes from other mononuclear cells. In 21 cases an insufficient number of control cells were measured. Seventy-two percent of the cytologic malignant cases were aneuploid. In contrast, in none of the cases with "atypia" and in only 2 of the cases "suspicious for malignancy" was aneuploidy present (2 of the remaining 32, 6%). From the cases with follow-up, a malignancy in the pleural fluid was present in 2 out of 17 cases with "atypia" and in 5 out of 10 with a "suspicious for malignancy" cytologic diagnosis, respectively. In conclusion, the additional diagnostic value of DNA image cytometry in cases with a cytological diagnosis of "atypia" or "suspicious for malignancy" is limited. Diagn. Cytopathol. 1999;21:112-116.

Adult↗
PubMed1999

Additional value of K-ras point mutations in bronchial wash fluids for diagnosis of peripheral lung tumours.

The purpose of this study was to examine the additional diagnostic value of K-ras point mutations in the clinical diagnosis of peripheral lung tumours. To this end, bronchial wash fluids obtained during bronchoscopy from patients suspected of having lung cancer were studied. Only those patients were investigated for whom the cytological diagnosis was not conclusive for malignancy. As a control group, patients without lung cancer were investigated. The method of "point mutation detection using the exonuclease amplification coupled capture technique" (Point-EXACCT) for analysis of K-ras codon 12 was performed in bronchial wash fluids and the corresponding tumour tissue, if available. K-ras point mutations were identified in 4 out of 19 (21%) bronchial wash fluids from patients without a decisive diagnosis of malignancy. The diagnosis of malignancy was further based on cytological examination of bronchial brush specimens, perthoracic needle aspiration, histological investigation of biopsy and resection specimens, needle aspiration of a lymph node in the neck and pleural fluid examination. Four of the patients who were K-ras-positive yielded positive malignant tissue via bronchoscopy even though the bronchial wash was negative for malignancy. The bronchial wash was positive for K-ras in two of the four patients whose tumour tissue demonstrated the K-ras mutations. Analysis of bronchial wash fluids from 11 patients without lung cancer revealed no K-ras codon 12 mutations. In conclusion, K-ras point mutations can be identified in bronchial wash fluids obtained during bronchoscopic procedures. K-ras can be used as a biomarker in the clinical diagnosis of lung cancer and may serve as an adjunct to cytology in lung cancer diagnosis.

Aged↗
PubMed1999

High-frequency oscillatory ventilation, partial liquid ventilation, or conventional mechanical ventilation in newborn piglets with saline lavage-induced acute lung injury. A comparison of gas-exchange efficacy and lung histomorphology.

It has been reported that, in diseased lungs, either partial liquid ventilation (PLV) or high-frequency oscillatory ventilation (HFOV) can improve oxygenation better and with less lung injury than conventional mechanical ventilation (CMV). This study was intended as a preclinical comparison between the effects of HFOV, PLV and CMV on gas exchange, lung mechanics and histology. Fifteen anesthetized newborn piglets, with respiratory insufficiency due to repeated saline lung lavage, were allocated to either a PLV, HFOV or CMV (n = 5 each) strategy, and treated for 4 h. Within 30 min of commencing therapy, PLV, HFOV, and CMV improved arterial PO2 (Pa,O2), alveoloarterial oxygen gradient (P(A-a),O2), oxygenation index (OI), venous admixture (va), and arterial PCO2 (Pa,CO2). After 4 h, oxygenation parameters (Pa,O2, P(A-a),O2, OI and venous admixture) were significantly better in the HFOV group than in the PLV group; the CMV group showed a higher Pa,O2 and lower OI than the PLV group. Gas exchange at the end of the experiment was not different from baseline in the HFOV and CMV groups. Lung histology and morphometry were performed after perfusion-fixation at endotracheal deflation pressure corresponding to mean airway pressure at the end of the experiment. Lung injury score and mean linear intercept were not different between the three treatment groups. We conclude that in this model, gas exchange improved significantly in all three ventilation strategies. Indices of oxygenation improved less during PLV. The saline lavage-induced acute lung injury model used as in this study, is less stable than previously thought. The final lung injury is not influenced by the ventilation strategy. We speculate that the impaired gas exchange during PLV is an expression of diffusion limitation and ventilation-perfusion mismatch in a recovering lung.

Animals↗
PubMed1999

Number and proliferation of clara cells in normal human airway epithelium.

Experimental pathologic studies suggest that Clara cells are one of the types of airway stem cells but the proliferation of Clara cells in human lungs has not yet been examined. The purpose of this study was to assess in conducting airways of normal human lungs: (1) the number of Clara cells; and (2) the contribution of Clara cells to the proliferation compartment. Samples of histologic normal tissue were taken from seven lungs obtained by autopsy. A triple sequential (immuno)histochemical staining was performed, using MIB-1 as a proliferation marker and anti-CC10 for the identification of Clara cells; subsequently, a PAS stain was carried out as a marker for goblet cells, as these cells were reported to be CC10-immunoreactive in an unknown proportion. Clara cells were virtually absent in the proximal airway epithelium. The number of Clara cells in the terminal bronchioles was 11 +/- 3% (mean +/- SD) and in respiratory bronchioles 22 +/- 5%. The overall proliferation compartment of the conducting airway epithelium was 0.83 +/- 0.47%; the contribution of Clara cells was 9%. In the terminal bronchioles 15% of proliferating airway epithelial cells were Clara cells, and in the respiratory bronchioles this number increased to 44%. The contribution of Clara cells to the proliferation compartment of normal human tracheobronchial epithelium is substantial, demonstrating a role of the Clara cell in the maintenance of the normal epithelium of the distal conducting airways in humans.

Adult↗
PubMed1998

Interaction between glucocorticoids and beta2-agonists: alpha and beta glucocorticoid-receptor mRNA expression in human bronchial epithelial cells.

Recent studies have suggested that regular use of beta2-agonists has adverse effects on asthma control, due to the cross-talk between cAMP responsive element binding proteins (CREB) and glucocorticoid receptors (GR). The aim of this study was to investigate the interaction between GR and CREB on cytoplasmic protein level with a gel mobility shift assay and to determine the effect of this interaction on mRNA levels by Northern blot analysis. After exposing human bronchial epithelial cells for 1 hr to either 1 microM terbutaline or budesonide, more binding of CREB and GR, respectively, was observed to their responsive elements in DNA. Simultaneous exposure to terbutaline and budesonide also increased the binding of CREB and GR to DNA. After 4 hr, both alpha and beta GR mRNAs were down-regulated by 1 microM budesonide. Simultaneous addition of 1 microM terbutaline prevented this down-regulation. Adding 100 times more budesonide compared to terbutaline again down-regulated both GR forms, although significantly less compared to the down-regulation induced by 1 microM budesonide alone. Addition of terbutaline to cells already exposed to budesonide did not reverse the GR mRNA expression within 44 hr. Similar results were obtained with metallothionein-2 (MT2) mRNA levels. In conclusion, beta2-agonists interfere with the GR function in human bronchial epithelial cells when given simultaneously, with this being overcome by sequential exposure of the cells to first glucocorticoids and later beta2-agonists.

Activating Transcription Factor 2↗
PubMed1998

Exonuclease enhances hybridization efficiency: improved direct cycle sequencing and point mutation detection.

Solution hybridization is an essential step in sequencing and some point mutation detection methods. In practice, this hybridization is hampered resulting in the need of additional purification of the amplification products. The use of T7 gene 6 exonuclease may lead to efficient production of single-stranded DNA. In this study, the effect of pretreatment with exonuclease on direct cycle sequencing and point mutation detection was analyzed. Exonuclease-treated products were directly cycle sequenced without further purification. This resulted in highly efficient quality improvement for sequencing allowing detection of heterozygotes. Point mutation detection by Point-EXACCT (exonuclease-amplification coupled capture technique) demonstrated detection of one cell containing a mutation in an excess of 75000 wild type cells. Exonuclease-enhanced detection methods offer simple, rapid detection strategies that are easily adaptable for widespread clinical laboratory use. With the use of exonuclease, the detection of heterozygosity using fluorescent cycle sequencing is becoming more reliable. The high sensitivity of Point-EXACCT due to the use of exonuclease makes it a highly promising method for large-scale screening of (pre)malignant changes in patients with a high risk for developing cancer.

DNA Mutational Analysis↗
PubMed1998

Increased proliferative activity and p53 expression in normal glandular breast tissue after radiation therapy.

Radiation used in breast-conserving therapy (BCT) for early breast cancer, to eradicate residual malignant cells after tumour resection, induces DNA damage and cell death. Little is known about the effect of the commonly used doses of radiation therapy on normal breast tissue. Under physiological conditions, p53 plays a role in maintaining genomic stability and regulating progression through the cell cycle. In normal glandular breast tissue, p53 expression is very low, as is proliferative activity. The purpose of this study was to investigate the levels of p53 expression and proliferative activity in non-malignant glandular epithelium of the breast after BCT. The immunohistochemical expression of p53 and Ki-67 was semiquantitatively correlated in non-malignant glandular epithelium in biopsies before and after BCT in 24 women with breast cancer. In 18 cases, a recurrence was diagnosed and in the remaining cases, the clinical suspicion was not histologically confirmed. In addition, in six cases with contralateral breast cancer, the same immunohistochemical evaluation was performed in tissue from both breasts. The mean interval between the two surgical interventions was 50 months. The percentage of p53 immunoreactive epithelial cells in normal breast tissue was significantly (P < 0.01) higher after radiation therapy than before in the ipsilateral side (0.2 per cent +/- 0.3 and 4.6 per cent +/- 4.5, respectively). Ki-67 immunoreactivity was also significantly increased (P < 0.001) after radiation therapy, from 0.6 per cent to an average of 4.8 per cent in epithelial cells. In contrast, in the patients with contralateral breast cancer, the levels of p53 and Ki-67 immunoreactivity in the normal glandular breast tissue were comparable to the ipsilateral side (P = 0.7 and P = 0.1, respectively). In conclusion, increased expression of p53 and Ki-67 is present in normal glandular breast tissue, even 2-5 years after radiation therapy.

Adult↗
PubMed1998

Gut permeability, intestinal morphology, and nutritional depletion.

Nutritional depletion increases the risk for postoperative complications. The intestinal barrier may be important in the underlying pathophysiologic mechanism. In this study, 26 patients were evaluated to determine whether nutritional depletion was related to gut integrity and intestinal morphology. Nutritional depletion was estimated by calculating percentage ideal body weight (PIB) or percentage ideal fat free mass (PIFFM). To assess gut integrity, a lactulose/mannitol (L/M) test was performed. Duodenal biopsies were taken, and villous height, crypt depth, number of IgA-producing plasma cells, intraepithelial lymphocytes (IELs), and proliferating index were determined. The L/M ratio was increased, and villous height was decreased in depleted patients. Depletion was not associated with differences in the number of immune cells or proliferating index. The number of IgA-producing plasma cells was positively correlated with the L/M ratio. This study shows that nutritional depletion is associated with increased intestinal permeability and a decrease in villous height.

Adult↗