Biomedical subjects
Publications and source records attributed to C A Seldenrijk.
A 71-year-old woman presented with a rapidly growing goitre which was diagnosed as chronic autoimmune thyroiditis. Despite treatment with levothyroxine, she developed progressive airway obstruction. Biopsy revealed a primary thyroid lymphoma which was successfully treated with radiotherapy.
BACKGROUND: Splice variants of CD44 play a causal role in the metastatic spread of pancreatic carcinoma in the rat. In previous studies we have shown that homologues of these CD44 isoforms (CD44v6) are overexpressed during colorectal tumorigenesis in man and that CD44v6 overexpression is associated with an unfavorable prognosis in this disease. In the present study we have assessed the prognostic significance of CD44 variants containing exon v5. In addition, we have used a panel of different antibodies against CD44v6 and applied a combined scoring system to improve its value as prognosticator. METHODS: Expression of CD44 variants was studied by immunohistochemistry on frozen tissue sections, and the prognostic value of the CD44 variant expression was assessed using univariate and multivariate analysis. RESULTS: Our studies show that expression of CD44v6, but not CD44v5, has significant prognostic value. Analysis of CD44v6 expression by means of a combined scoring system, on the basis of a panel of three different monoclonal antibodies (mAbs), makes CD44v6 a highly significant prognostic marker that is independent of Dukes stage, tumor grade, or tumor localization. CONCLUSION: Assessment of CD44v6 expression by a combination of mAbs yields an independent prognosticator that may be of value in identifying patients with a high propensity to develop distant metastasis.
Explore the source record for details and available documents.
Kikuchi's lymphadenitis was first recognized almost 25 years ago in Japan as a histopathologically specific reactive lymphadenitis without clear clinical correlates. The benign self-limiting clinical course and the notorious danger of misdiagnosis as malignant lymphoma together make it important to recognize this lymph node reaction type. We describe 2 typical case histories-young women with a cervical localisation.
Explore the source record for details and available documents.
PURPOSE: We evaluated the prognostic impact of neuroendocrine differentiation in prostate cancer with regard to the onset of endocrine therapy failure. MATERIALS AND METHODS: A retrospective study was performed on 72 transurethral resection specimens from patients who subsequently underwent endocrine therapy for prostate cancer and were followed for 44 to 95 months. Progression-free interval was recorded. Distribution pattern and proportion of neuroendocrine cells were examined in transurethral resection specimens. Neuroendocrine cells were identified based on immunoreactivity for chromogranin A. RESULTS: Of 32 patients with progressive disease 27 died of prostate cancer. Chromogranin A positive cells were found in 40 of the 72 prostate cancers (55%). In a Cox proportional hazards analysis neuroendocrine differentiation of the tumor showed a negative correlation with progression-free survival (p = 0.022), which proved to be independent of the Gleason score (p < 0.001). CONCLUSIONS: Our results support the view that neuroendocrine differentiation in prostatic adenocarcinomas is a prognostic factor for progressive disease under subsequent endocrine therapy. This prognosticator acts independently of tumor grade.
A 49-year-old female with rheumatoid arthritis developed liver cirrhosis after a cumulative dosage of 6 g methotrexate (MTX). There were mild liver enzyme abnormalities, decreased liver synthesis function and possible signs of portal hypertension. After stopping MTX all laboratory abnormalities disappeared except for a mild thrombocytopenia. Risk factors and guidelines for monitoring liver toxicity during MTX treatment in rheumatoid arthritis are discussed.
Explore the source record for details and available documents.
To help determine whether adenocarcinomas of the proximal and distal large bowel reflect distinct entities, the expression of two splice variants of the metastasis-associated cell adhesion molecule CD44, carrying exons v5 and v6 respectively, was investigated retrospectively in fresh frozen samples of 23 proximal and 41 distal carcinomas by immunohistochemical staining with specific anti-CD44v5 monoclonal antibody VFF8 and anti-CD44v6 monoclonal antibodies VFF4 and VFF7. Tumours were staged as: Dukes A, 0; Dukes B, 27; Dukes C, 31; and Dukes 'D', six. Compared with distal tumours, proximal lesions expressed significantly more CD44v5 (96 versus 87 per cent, P = 0.02) and CD44v6 (83 versus 61 per cent, P = 0.01). CD44v5 and CD44v6 are considered markers for tumour progression and aggressive behaviour. Their high expression in proximal carcinomas seems to contrast with the general belief that these tumours show less aggressive behaviour than left-sided lesions. Further study of the biological significance of the expression of CD44 splice variants is therefore needed.
CD44 variants containing v6 confer metastatic potential to rat carcinoma cell-lines. In man, CD44v6 is increasingly expressed during colorectal tumour progression. In 68 colorectal carcinoma patients, survival analysis showed that CD44v6 expression in the tumours was associated with tumour-related death. In patients who had an apparently radical resection of their primary tumour, CD44v6 expression had prognostic value independent of Dukes' stage. CD44v6 expression may reflect propensity for metastasis after apparently curative surgery, making adjuvant therapy an option in these patients.
The monoclonal antibody OV-TL 12/30, which detects keratin 7, was tested for its usefulness in cytologic diagnosis by reincubating previously Papanicolaou-stained slides. For this purpose malignant effusions of 73 patients with histologically confirmed cancers of the colon, ovary, mesothelium, breast, lung, esophagus, pancreas, urinary bladder, stomach, kidney, and prostate were used. All malignant cells from ovarian adenocarcinomas were positive, whereas malignant cells from colonic adenocarcinomas and malignant mesotheliomas were negative. Adenocarcinomas of gastric, renal, pancreatic, esophageal, and mammary origin demonstrated variable staining. Transitional cell carcinomas were positive, whereas squamous and small cell lung carcinomas were negative. Because OV-TL 12/30 does not react with normal and atypical mesothelial cells in these preparations, this reagent is a valuable tool in distinguishing benign mesothelial cells and adenocarcinoma cells. The authors' results demonstrate that this antibody is an excellent tool in the differential diagnosis of malignant cells in effusions and can be used in routinely stained cytologic specimens to determine primary tumor localization. In addition to its ability to distinguish between ovarian and colonic adenocarcinomas, its negativity in mesotheliomas may prove helpful in several diagnostic considerations.
A fatal case of fulminant hepatic failure that occurred in the neonatal period is reported in a premature infant born after 27 4/7-weeks' gestation. Immediately after birth the infant had severe hypoxia and hypotension resulting from birth asphyxia, hypovolemic shock, and septicemia. At autopsy, histological appearance of the liver showed virtually total hepatocellular necrosis without features of fibrosis. Although the exact cause of hepatocellular injury cannot be fully ascertained, it is assumed that hypoxia and hypotension must have been the predominant factors leading to massive hepatic necrosis.
AIMS: To investigate whether counting cells containing immunoglobulin (Ig) subclass in colonic biopsy specimens of patients with chronic inflammatory bowel disease, in addition to conventional histological evaluation, can improve the differentiation of patients with Crohn's disease from those with ulcerative colitis. METHODS: The colonic and rectal biopsy specimens of 40 patients with chronic inflammatory bowel disease, comprising 20 patients with Crohn's disease and 20 with ulcerative colitis, were used and sections were stained specifically for IgA, IgM, and IgG heavy chains using an indirect immune peroxidase method. The immunoglobulin subclass containing cells were counted using an ocular grid counting method in a light microscope. A linear stepwise discriminant analysis was performed on Ig subclass containing cell counts in combination with 16 reproducible histological features. The results of this discriminant analysis were compared with the results of the discriminant analyses in which only the histological features were used. RESULTS: Applying stepwise discriminant analysis, two histological features (an excess of histiocytes in the lamina propria and the villous or irregular aspect of the mucosal surface) in combination with IgMax were selected as the most discriminatory parameters that distinguish Crohn's disease from ulcerative colitis. IgMmax was defined as the maximum value of the mean percentage of IgM containing cells over all the biopsy locations. The use of this combination resulted in a better classification in 20% of the patients with Crohn's disease and in 9% of the patients with ulcerative colitis compared with the use of histological features alone. CONCLUSIONS: Morphometric enumeration of Ig subclass containing cells in colonic mucosal biopsy specimens has diagnostic value as a means of differentiating individual patients with Crohn's disease from those with ulcerative colitis.
There is evidence that gastrostomy can induce gastroesophageal reflux (GER). We used pH monitoring in piglets to evaluate GER after gastrostomy and to assess the effect of anterior gastropexy. Oesophageal pH studies were performed before and after gastrostomy with (8) and without (9) anterior gastropexy. The reflux score was the percentage of time that pH was below 4.0. Short episodes (mean reflux score 2.6%; range, 1.6% to 30%) of GER occurred in half of the animals before surgery. After gastrostomy, reflux episodes occurred more frequently (77% of animals) and were more prolonged (mean reflux score 35.2%; P less than .001). Anterior gastropexy with gastrostomy prevented GER in all 6 piglets with an intact gastropexy. In two animals with reflux after gastrostomy with gastropexy the gastropexy appeared dehiscent at autopsy. Microscopic ulcerative esophagitis was present in more than half the animals with a positive pH study. We conclude that (1) piglets demonstrate short episodes of spontaneous GER; (2) gastrostomy increases the duration and incidence of the GER episodes; (3) anterior gastropexy prevents gastrostomy-induced GER in piglets; and (4) gastrostomy in piglets is a suitable model for studying GER. We advocate protective anterior gastropexy when performing a feeding gastrostomy.
In a prospective blind evaluation of multiple colonic mucosal biopsy specimens, 45 clinically well defined patients with chronic inflammatory bowel disease (21 Crohn's disease and 24 ulcerative colitis) and 16 control subjects (seven normal subjects and nine patients with diverticular disease) were studied to identify reproducible histopathological features which could distinguish chronic inflammatory bowel disease (CIBD) from non-CIBD and Crohn's disease from ulcerative colitis. Using kappa statistics 16 of 41 histological features were sufficiently reproducible for further stepwise discriminant analysis to differentiate between CIBD and non-CIBD, and between Crohn's disease and ulcerative colitis. Using the combination of three features (an increase of lymphocytes and plasma cells in the lamina propria, the presence of branching of crypts, and neutrophils in the crypt epithelium) we were able to distinguish CIBD from non-CIBD in 89% of the cases with high probability (p greater than 0.85). To separate Crohn's disease from ulcerative colitis three features (an excess of histiocytes in combination with a villous or irregular aspect of the mucosal surface and granulomas) had a high predictive value. Using these features 70% of Crohn's disease patients and 75% of ulcerative colitis patients were correctly classified with a high probability (p greater than 0.85). These findings indicate that the pathologist is dependent on the presence of only a few histological features for a reliable classification of Crohn's disease and ulcerative colitis.
Collagenous colitis is a rare condition characterized clinically by chronic diarrhea and histologically by a thickened subepithelial collagenous band in colonic biopsies in an endoscopically normal colon. Familial occurrence of collagenous colitis has to our knowledge never been described. Here we report two families in which two first-degree related members suffered from collagenous colitis. In one family, two sisters were affected by chronic diarrhea and autoimmune disorders such as thyroid disease, rheumatoid arthritis, and pernicious anemia. Collagenous colitis was diagnosed in one of these sisters, based on colonic biopsies. Colonic biopsies of the other sister showed microscopic colitis. Review of colonic biopsies of this patient taken 11 years earlier, however, showed definite histological features of collagenous colitis. In the other family, in a father and son, both with diarrhea for several years but not suffering from any other diseases, a diagnosis of collagenous colitis was made on colonic biopsies. Human leukocyte antigen (HLA) typing showed that only the HLA A2 antigen was present in all 4 patients.
A mycobacterial aetiology has been suggested for Crohn's disease. A slow growing mycobacterium, biochemically and genetically identical to M paratuberculosis, the causative agent of enteritis in ruminants (Johne's disease), has been isolated from gut specimens of patients affected by Crohn's disease. If M paratuberculosis or other mycobacteria play a role in the pathogenesis of Crohn's disease, then patients may have been sensitised to these mycobacteria or show an anergy immune reaction. We therefore investigated the T-cell mediated immune response to sonicates of M paratuberculosis, M kansasii, M avium, and M tuberculosis in 35 patients with Crohn's disease, 28 with ulcerative colitis, and 25 controls using a macrophage inhibition factor assay on peripheral blood lymphocytes. Two types of reaction patterns were identified--that is, 'responders' (subjects with a macrophage inhibition factor assay in which a dose response relation was present and a percentage of inhibition exceeding 20%), and 'non-responders'. There was no significant difference in the prevalence of responders (59%-80%) and non-responders (20%-41%) to these mycobacteria between the group of Crohn's disease, ulcerative colitis, and control group. We found also that a large proportion of controls showed T-cell immunisation to the mycobacteria which supports the contention that the antigens are practically commensal. Our results do not support the proposed involvement of mycobacteria in the pathogenesis of Crohn's disease.
Brequinar sodium (NSC 368390; DUP 785) is a new inhibitor of pyrimidine de novo biosynthesis which has completed Phase I clinical trials within the framework of the Early Clinical Trials Group of the European Organization for Research and Treatment of Cancer (EORTC). The main side effects of this compound are myelosuppression, nausea and vomiting, stomatitis and/or mucositis, and skin rash. In this report, the authors describe the pattern of mucocutaneous side effects of Brequinar sodium in patients who received the drug by four different schedules: (1) short-term intravenous (IV) infusion every 3 weeks; (2) weekly; (3) twice weekly; and (4) five times daily every 4 weeks. Mucocutaneous toxicities of Brequinar sodium included mainly cytotoxic reactions (stomatitis and/or mucositis and skin rash). However, rare episodes of local reactions (phlebitis at the site of injection), photosensitivity reactions (to sun light), angioneurotic edema, and localized secondary hyperpigmentation of the inflamed skin also occurred. Stomatitis and/or mucositis appeared to be dose-dependent and schedule-dependent. The skin rash consisted of a drug-induced toxic dermatitis which occurred mostly at the highest dose levels. Initial recommendations for the management of mucocutaneous toxicities of Brequinar sodium during Phase II trials are discussed.