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Biomedical subjects

C J Meyer

Publications and source records attributed to C J Meyer.

At least 37 records · Page 2Linked to original sources

Two colour DNA in situ hybridization for the detection of two viral genomes using non-radioactive probes.

Methods for the simultaneous detection of two virus types in cytological preparations or tissue sections by non-radioactive in situ hybridization were investigated. As a model system, CaSki cells, which have human papilloma virus type 16 (HPV16) DNA integrated in their cellular genome, were in vitro infected with Herpes simplex virus 2 (HSV2). DNA probes for both viruses were labeled with biotin, acetylaminofluorene (AAF), and transaminated-sulfonated cytosine (TS-modified). Best results were obtained when a mixture of biotinated and haptenized DNA probes (AAF- or TS-modified) was used for hybridization. The biotinated hybrid was demonstrated with a streptavidin-biotinated alkaline phosphatase staining reaction, whereas the haptenized hybrid was visualized by an indirect peroxidase method. Visualisation of both viral DNAs in the same cell was possible by a combination of biotinated HPV16 DNA and haptenized HSV2 DNA.

DNA Probes, HPV↗

A double-blind, placebo-controlled trial of acitretin for the treatment of psoriasis.

Acitretin, the active metabolite of etretinate, has the clinical advantage of a much shorter terminal elimination half-life. We report the results of a double-blind, placebo-controlled trial of acitretin (Soriatane) in 15 patients with moderate to severe psoriasis. Patients received 25 mg or 50 mg daily of acitretin or placebo in a double-blind fashion for 8 weeks and then were given 25 to 75 mg acitretin daily during an open study. Only two placebo patients completed the double-blind phase; one patient's psoriasis worsened, and one showed no significant change. All 15 patients then completed at least 8 weeks with 25 to 75 mg acitretin daily, with a moderate change in erythema, scaling, and induration (mean 28% to 37% improvement) but with minimal change in the percentage of body surface area involved. Prolonged treatment (greater than or equal to 20 weeks) with acitretin resulted in further significant improvement and a 44% reduction of involved surface area from baseline.

Acitretin↗

Retrospective study of prognostic importance of DNA flow cytometry of urinary bladder carcinoma.

Cellular DNA content was determined by flow cytometry on routinely processed paraffin sections of 61 primary and untreated transitional cell carcinomas of the urinary bladder, and correlated with tumour grade and stage and clinical follow up. All 16 (25%) grade 1 carcinomas were diploid and all 11 (20%) grade 3 tumours were aneuploid. The 34 (55%) grade 2 carcinomas comprised 13 (40%) diploid and 21 (60%) aneuploid cases. Among the 37 superficial carcinomas (stage Ta and T1), 25 (65%) were diploid; 20 (85%) of the 24 advanced tumours (stage T2 to T4) had aneuploid tracings. Ploidy was a significant prognostic indicator (p: 0.006) of five year survival. The initial presence of aneuploidy in superficial bladder carcinoma (stage Ta and T1) is a strong argument for more aggressive treatment than is customary.

Aged↗

Use of statistical evaluation of antigen profiles in differential diagnosis between colonic and ovarian adenocarcinomas.

A study was carried out to determine whether it was possible to classify colonic and ovarian adenocarcinomas by their antigen profile. Colonic and ovarian adenocarcinomas were immunostained with a panel of antibodies which have a limited specificity for colon (parlam-4, 19.9, anti-secretory component) and ovary (OV-TL3 and OC125) and the most discriminatory antibodies were selected by stepwise linear discriminant analysis. For frozen material OV-TL3 and OC125 were the best classifying antibodies. Although OC125 had better discriminative power, for paraffin wax embedded material parlam-4 was selected as the best classifying antibody. OC125 had no additional effect on the classification of a tumour. These antibodies were subsequently tested on an independent test set of primary and metastatic adenocarcinomas of colonic and ovarian origin. When ovarian posterior probabilities of less than 0.1 and greater than 0.9 were selected as cut off points for a positive identification of colonic or ovarian origin (jackknifed classification method), no adenocarcinoma was incorrectly identified as ovarian carcinoma in frozen material. The same trend was noticed for paraffin wax embedded material. Statistical analysis of antigen profiles can be helpful in defining the colonic or ovarian origin of an adenocarcinoma when routine microscopy does not yield a definitive result.

Adenocarcinoma↗

Invasion of laryngeal cartilage by cancer: comparison of CT and MR imaging.

Forty-two patients with laryngeal carcinomas were examined with computed tomography (CT) and magnetic resonance (MR) imaging. The accuracy of both CT and MR imaging in the depiction of cartilage invasion was evaluated in 16 patients by comparing findings at CT and MR with pathologic findings. Calcified cartilage that has been invaded by cancer is frequently seen on CT scans as having an intact contour. Tumor approaching nonossified cartilage may simulate cartilage invasion. On T1-weighted MR images, invaded marrow of ossified cartilage is of intermediate signal intensity, allowing it to be differentiated from normal bone marrow. On proton-density images, tumor is of increased signal intensity, which allows it to be differentiated from nonossified cartilage. In our experience, the specificities of CT and MR imaging were approximately equal (91% and 88%, respectively), but CT had a considerably lower sensitivity than MR (46% vs. 89%). Gross movement artifacts, which resulted in nondiagnostic images, occurred in 16% of the MR examinations. MR imaging is recommended as the modality of choice in the diagnosis of cartilage invasion.

Aged↗

The expression of intermediate filaments and mam-6 antigen in relation to the degree of morphologic differentiation of carcinoma of the head and neck: diagnostic implications.

In this study, the immunoreactivity of several cytokeratin antibodies; 115 D8, a monoclonal antibody against MAM-6, an epithelial membrane antigen; and two vimentin antibodies, is examined in relation to the degree of morphologic differentiation in carcinomas of the head and neck. The results indicate that a relationship exists between the degree of morphologic differentiation and the expression of cytokeratin, MAM-6, and vimentin, as detected by polyclonal antikeratin, 115 D8 and anti-vimentin. Expression of cytokeratin and MAM-6 is reversely related to vimentin. Polyclonal anti-keratin; CAM 5.2, a monoclonal antibody against cytokeratin 8, 18 and 19; and 115 D8, used in combination, were still able to identify the epithelial nature of undifferentiated/spindle cells. Since these immunohistochemical markers precede light microscopic detectable signs of epithelial differentiation, they can be used for the identification of the epithelial nature of undifferentiated/spindle tumors of the head and neck.

Antigens, Differentiation↗

Prospective evaluation of prognostic value of morphometry in patients with primary breast cancer.

In a prospective study the predictive value of a multivariate morphometric prognostic index was evaluated in 195 patients with primary breast cancer who had not been treated with any form of chemotherapy or hormonal treatment. The presence or absence of distant tumour recurrence combined with the scores of the prognostic index were compared with the survival curves predicted in a previous study. The value of the presence of lymph node metastases, number of positive nodes, tumour size, mitotic activity index, and oestrogen receptor status in prediction of prognosis were also investigated. In agreement with the results of the previous retrospective study, the prospective use of the index had the strongest predictive prognostic value, followed by the mitotic activity index. Statistical analysis showed that the actual prognoses of 43 of the 195 patients (22%) were more accurately determined by the prognostic index rather than by using the presence of the lymph node metastases as the classifying variable. The prognostic index is consistently reproducible by different technicians; it is a reliable method of predicting distant recurrence of tumour and hence the prognosis of patients with primary breast carcinoma. It provides more prognostic information than the presence of lymph node metastases alone, and the index should be incorporated in routine pathology reports.

Adult↗

MRI of normal or cancerous laryngeal cartilages: histopathologic correlation.

MRI appearances of laryngeal cartilages, normal or invaded by cancer, are still relatively unfamiliar to most clinicians. Twelve primary laryngeal tumors out of a series of 65 patients which have been investigated by MRI were examined postoperatively by macroscopic and microscopic sectioning of the surgical specimens. Images were obtained with a 0.6 Tesla superconductive system using a solenoid surface coil. The authors emphasize the value of a combined use of T1-weighted and balanced (relatively T2-weighted images with still T1-characteristics) Spin Echo images. T1-weighted images permit differentiation between pathological and normal bone marrow. Balanced images allow separation between nonossified cartilage and tumor tissue. MRI is an additional tool in the diagnostic workup of cartilage invasion by tumor.

Aged↗

Morphometry of breast cancer. I. Comparison of the primary tumours and the axillary lymph node metastases.

In 234 patients with primary breast cancer, morphometry was performed of three groups of tumour cells: 1. in the primary tumours without lymph node metastases (PRN); 2. in primary tumours with lymph node metastases (PRP) and; 3. in the axillary lymph node metastatic deposits (LMD). The morphometrical analysis included the cellularity index, the mitotic activity index and seven nuclear features. The highest mitotic activity indices (mean: 14.1) were found in the metastatic deposits (LMD), the lowest (mean: 12.5) in the lymph node negative primary tumours (PRN), whereas the lymph node positive primary tumours (PRP) fell in between (mean: 13.2). The cellularity index shows a similar, though reciprocal, trend. The largest standard deviations of the nuclear features were found in primary tumours with lymph node metastases (PRP). In contrast, the metastatic (LMD) nuclei had the smallest standard deviations. The nuclei of the latter are therefore more regular in size and shape. The differences found are not sufficiently large to distinguish PRN and PRP with an acceptable accuracy (the efficiency, sensitivity or specificity did not exceed 67% irrespective of the decision threshold used). Comparison of primary tumours with lymph node metastases and the metastatic deposits, from the same patients, revealed significant correlations of all morphometric features with the exception of the nuclear shape factor and the nuclear axes ratio. Thus, the nuclei of the metastatic cells in general are identical to the nuclei in the primary tumour from which they arise, but in a subset of patients the metastatic tumour cells have much more monomorphous ellipsoid nuclei. Further investigations are needed to see whether this phenomenon indicates a different malignant course.

Adult↗

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↗

Carcinoembryonic antigen expression and peanut agglutinin binding in primary breast cancer and lymph node metastases; lack of correlation with clinical, histopathological, biochemical and morphometric features.

In a group of 335 patients with primary breast carcinoma the presence of immunoreactive carcinoembryonic antigen (CEA) and the binding of the lectin peanut agglutinin (PNA) in the primary carcinoma and in axillary lymph node metastases were investigated. The correlation between these results and a variety of established clinical, histopathologic, morphometric and biochemical prognosticators was studied. These features included lymph node status, tumour diameter, tumour type, nuclear grade, histologic grade, oestrogen receptor status, mitotic activity index and a number of nuclear measurements. The results indicate that CEA immunoreactivity of and PNA binding to tumour cells in primary breast carcinomas or lymph node metastases do not correlate with established prognostic factors in breast cancer.

Adult↗

Monitoring serum CEA in women with primary breast tumours positive for oestrogen receptor and with spread to lymph nodes.

Serum carcinoembryonic antigen concentrations (serum CEA) in 80 patients with primary breast cancer were measured preoperatively, one month after operation, and thereafter serially every third month. These data were related to histological and morphometric features of the primary breast carcinoma and the lymph node metastases and to clinical follow up data. Analysis of the serum CEA values showed significant correlations with size of tumour, the presence of lymph node metastases, oestrogen receptor, and occurrence of distant metastases. Furthermore, the results indicated that serial determination of serum CEA in the first two years after operation may be useful in monitoring for the occurrence of distant metastases in patients with metastatic spread to lymph nodes and with large (greater than or equal to 2 cm) primary breast tumours positive for oestrogen receptor. In agreement with other studies, however, it was found that the predictive value of serum CEA concentrations in general is weak and costs may prohibit the implementation of the routine assessment of CEA concentrations.

Adult↗

Quantitative morphometry of squamous cell hyperplasia of the larynx.

The histopathological diagnosis of squamous cell hyperplasia of the larynx is very subjective. Since morphometry is highly reproducible, this method was applied to routine processed slides of 45 such lesions to assess objectively the epithelial characteristics. In each case measurements of nuclei of 50 cells in the basal, intermediate, and superficial cell layers were carried out. The data were analysed statistically. The findings suggest that quantitative morphometry may be helpful for the histopathological classification of squamous cell hyperplasia of the laryngeal mucosa.

Cell Nucleus↗

Clinical and immunological follow-up of patients with severe renal disease in Wegener's granulomatosis.

Clinical and immunological data are reported of 12 patients suffering from Wegener's granulomatosis and severe renal involvement. Although 9 patients recovered from their acute illness, a long-term follow-up a relapse occurred in 4 of these 9 patients. Therefore, lifelong follow-up in this group patients seems to be mandatory. Extensive immunological investigations did not provide evidence for humoral mechanisms underlying the pathogenesis of this disease; T lymphocyte subsets in peripheral blood as well as functional reactivity of lymphocytes in vitro were also normal. However, none of the patients was able to mount a primary cellular immune response in vivo. On the other hand, kidney biopsy specimens obtained before the initiation of drug therapy revealed periglomerular and interstitial cellular infiltrations consisting predominantly of T lymphocytes with a ratio Leu 3a (OKT4)/Leu 2a (OKT8) of 5:1. This may indicate that a type IV (delayed-type) hypersensitivity reaction takes place in the kidney. These findings suggest that an abnormal cellular immunoreactivity plays a major role in the pathogenesis of Wegener's granulomatosis.

Adolescent↗

Hyperimmunoglobulinaemia D and periodic fever: a new syndrome.

Six patients of Dutch ancestry with a long history of recurrent attacks of fever of unknown cause were found to have a high serum IgD level and a large number of plasma cells with cytoplasmic IgD in the bone marrow. Because the clinical picture in some ways resembled that of familial Mediterranean fever (FMF), sera of patients with FMF were also investigated; only one of eight such patients had a raised serum IgD.

Adolescent↗

Increased numbers of IgE containing cells in gastric and duodenal biopsies. An expression of food allergy secondary to chronic inflammation?

Gastric and duodenal biopsies from 2543 patients with abdominal complaints were sent to the Department of Pathology of the Stichting Samenwerking Delftse Ziekenhuizen in 1980 and 1981 and screened for plasma cells containing IgE using an indirect immunoperoxidase technique. Increased numbers of IgE containing cells were found in 2.6% of the patients. These patients all suffered from a variety of chronic non-specific inflammatory disorders of the upper gastrointestinal tract. No specific clinical, endoscopical, or histological picture could be found. The results suggest that increased numbers of plasma cells containing IgE in biopsies from the upper gastrointestinal tract are an expression of IgE mediated type I allergy presumably to food constituents as a secondary complication of chronic non-specific gastric and duodenal inflammation in these patients.

Cell Count↗

Mononuclear cells in renal allografts. Correlation with peripheral blood T lymphocyte subpopulations and graft prognosis.

Cellular infiltrates in 20 renal allograft biopsies taken at the time of acute rejection episodes were analyzed with antibodies reactive with monocytes (BRL antihuman monocyte monoclonal antibody), T lymphocyte subpopulations (OKT- and Leu-series of monoclonal antibodies), and B lymphocytes (heterologous antihuman IgM antibodies). For demonstration of the various mononuclear cells, an indirect immunoperoxidase technique was used. The number of monocytes in the infiltrates varied from 10-20%; the number of B lymphocytes was always below 10%. The T lymphocytes accounted for 50-90% of the total number of mononuclear cells. The OKT4/OKT8 ratios for the T lymphocytes in the graft infiltrates were correlated with the peripheral blood OKT4/OKT8 ratios measured by indirect fluorescence and flow cytometry. The OKT4/OKT8 ratios for perivascular infiltrates correlated far better with peripheral blood OKT4/OKT8 ratios (r = 0.72) than did the OKT4/OKT8 ratios for interstitial infiltrates (r = 0.58). Low or inverted OKT4/OKT8 ratios and low or inverted Leu 3a/Leu 2a ratios were associated with a high risk of irreversible graft rejection (P less than 0.001 for perivascular infiltrates).

Antibodies, Monoclonal↗