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Biomedical subjects

K W Schmid

Publications and source records attributed to K W Schmid.

At least 19 recordsLinked to original sources

[Hyperplasia of the thyroid gland].

Hyperplasia of the follicular epithelium (goitre) is the most common morphological change in the thyroid seen by the pathologist. The present paper deals with the aetiology, epidemiology and clinical features of thyroid hyperplasia and its differential diagnosis from thyroid adenoma. Neoplastic hyperplasia of the calcitonin-producing thyroid C cells gives rise to familial medullary carcinoma. The second part of the paper deals with the definition of neoplastic C cell hyperplasia and its discrimination from physiological C cell hyperplasia.

Humans↗

[Inflammatory diseases of the thyroid gland. Epidemiology, symptoms and morphology].

Inflammation of the thyroid gland makes up approximately 20% of all thyroid diseases. According to the clinical course, thyroiditis has been subdivided into acute, subacute, and chronic forms. Recent classifications are based on the fact that the majority of thyroiditis cases have an autoimmune background. The most common form of this disease is autoimmune thyroiditis (AIT), with or without subclinical/manifest hypothyroidism; less common forms of autoimmune thyroiditis comprise subacute granulomatous (de Quervain's) thyroiditis, postpartum thyroiditis, silent ("painless") thyroiditis, and invasive-sclerosing thyroiditis (Riedel's thyroiditis). Non-autoimmune thyroiditis is very rare (acute suppurative thyroiditis, radiation thyroiditis). Thyroiditis is both clinically and morphologically an important differential diagnosis of thyroid tumours. The present paper deals with the epidemiology, clinical course, and morphology of thyroiditis, knowledge of which is essential for the examination of cytological and histological thyroid specimens.

Diagnosis, Differential↗

[Hyperplasia and tumors of the parathyroid glands].

Hyperparathyroidism is mainly caused by hyperplasia or adenomas of the parathyroid glands. Formerly, the therapeutic strategy depended on the morphological diagnosis (preferentially already made intraoperatively by examination of frozen sections). Today, however, the extent of parathyroid surgery is in many cases guided both by substantial improvements in the preoperative clinical diagnosis as well as the intraoperatively determined decrease in the serum parathyroid hormone level. Nevertheless, the pathologist should be familiar with the differential diagnostic criteria of parathyroid hyperplasia, adenoma, and carcinoma.

Humans↗

[Biochips in bladder cancer research].

The techniques of DNA microarrays, protein arrays, and tissue microarrays complement one another and in the future the combination of these methods will possibly enable the detection of genes specific for bladder cancer. The SELDI technology (surface-enhanced laser desorption/ionization) will then be used to prove if the genes are translated into proteins and if those proteins have a relevant effect on the development and progression of the cancer disease. The consequence is the facilitation of the development of prognostic markers for this disease entity, which can then be easily tested in a large study population by tissue microarray. Beyond the gain of new insights into the biological understanding of the development and progression of bladder cancer, these techniques will hopefully enable the design of new therapeutic concepts, which apply to the individual biology of the tumor.

Biopsy↗

[Thyroid tumors].

The vast majority of thyroid tumours are epithelial. In contrast to thyroid adenoma, which is a common tumour, thyroid carcinomas make up only 1% of all human malignancies. Routine pathology is regularly confronted with a differential diagnosis involving thyroid adenoma and carcinoma, as well as particular variants of these tumours. This paper deals with the standardised gross and histological examination, as well as the impact of immunohistochemistry and intraoperative frozen sections on thyroid pathology.

Carcinoma, Papillary↗

Diagnostic value of high-resolution B-mode and power-mode sonography in the follow-up of thyroid cancer.

OBJECTIVE: Ultrasonography is an established diagnostic modality in the follow-up of thyroid cancer. Color flow Doppler has been proposed by some authors as an additional tool for differentiating benign from malignant cervical lesions in various types of head and neck cancer. Over the last few years, a new generation of high-resolution ultrasound platforms with the "power-mode" feature has become available, that also enables the imaging of small vessel blood flow. The objective of our study was to find ways of optimizing the differentiation of benign and malignant cervical tumors in thyroid cancer follow-up by means of sonography. METHODS: Hundred and twelve cervical lesions in 90 patients with thyroid cancer were evaluated by high-end ultrasonography (Sonoline Elegra, Siemens) using a small-part transducer (7.5 L 40, Siemens). B-mode sonography was performed at a frequency of 8 MHz. The Solbiati index (SI= ratio of largest to smallest diameter), configuration, echogenicity, intranodular structures, and margins were assessed. Perinodular and intranodular blood flow was evaluated by color flow Doppler (PRF 1250 Hz for conventional color flow Doppler, 868 Hz for power-mode Doppler). Possible malignancy was validated by histology, cytology, scintigraphy, and follow-up. Thirty five lesions were benign (diameter 0.4-3.0 cm) and 77 were malignant (0.4-5.4 cm). The patients were randomized into a test group and a learning group to determine the diagnostic value of various ultrasound criteria by means of statistical analysis. In the learning group, decision rules based on the dichotomized criteria were developed using a logistic regression model. Sensitivity and specificity of these decision rules were then evaluated in the test group. RESULTS: The presence of an echocomplex pattern or irregular hyperechoic small intranodular structures (criterion A) and the presence of an irregular diffuse intranodular blood flow (criterion B) are the best indicators of malignancy, whereas an SI >>2 is highly indicative of benign changes. Color flow Doppler is a useful addition to B-mode scanning for distinguishing benign and malignant neoplasms in the follow-up of thyroid cancer. Power-mode Doppler sonography significantly improves imaging of perinodular and intranodular blood flow when compared with conventional color flow Doppler. CONCLUSION: We propose the following decision rules based on a combination of the criteria above: (A) and (B) fulfilled: malignant, if SI< or =4; (B) but not (A) fulfilled: malignant, if SI< or =3; (A) but not (B) fulfilled: malignant, if SI< or =2; neither (A) nor (B) fulfilled: malignant, if SI approximately equal to 1 (sensitivity: 90%; specificity: 82%; accuracy 88%).

Adult↗

Multicenter study differentiated thyroid carcinoma (MSDS). Diminished acceptance of adjuvant external beam radiotherapy.

AIM: The Multicenter Study Differentiated Thyroid Carcinoma (MSDS) is an ongoing study in Germany, Austria, and Switzerland on the clinical benefit of adjuvant external beam radiotherapy (RTx) for locally invasive differentiated thyroid carcinoma (DTC) in TNM stages pT4 pN0/1/x M0/x (5th ed. 1997). METHODS: MSDS was designed as a prospective randomized trial. Patients receive thyroidectomy, radioiodine therapy (RIT) to ablate the thyroid remnant, and TSH-suppressive L-thyroxine therapy with or without RTx after documented elimination of cervical iodine-131 uptake (http://msds-studie.uni-muenster.de). RESULTS: 311 patients were enrolled between January 2000 and March 2003. 279 patients met the trial's inclusion criteria. 45 consented to randomization, of whom 17 were randomized into treatment arm A (RTx) and 18 into arm B (no RTx). Advised by the trial's independent Data Monitoring and Safety Committee, the MSDS steering committee decided to terminate randomization in April 2003 and continue MSDS as a prospective cohort study. 23 of the 234 patients in the observation arm of the trial were prescribed RTx by their physicians. Thus, 14% of the trial cohort were randomized or assigned to receive RTx (in-tention-to-treat analysis). In contrast, at least 44% of all patients with pT4 papillary DTC in Germany in the nation-wide PCES study underwent RTx in 1996 (p <0.001, chi(2)-test). CONCLUSIONS: Acceptance of external beam RTx as a treatment modality for DTC has receded to a degree that accrual of a sufficient number of patients for a randomized trial has been impossible. Observation of the trial cohort is continued in order to assess clinical event rates with and without RTx and chronic RTx toxicity.

Combined Modality Therapy↗

Increased expression of metallothionein in inflammatory bowel disease.

OBJECTIVE: Metallothioneins (MT) are cytoprotective against the damaging effects of oxygen-derived free radicals. Therefore MT may be involved in defence mechanisms to counter Crohn's disease (CD) and ulcerative colitis (UC). MATERIALS: 107 routinely processed tissue samples from 22 patients with CD and 48 patients with UC were tested with the monoclonal anti-MT antibody E9. METHODS: Immunohistochemistry was used to assess MT staining in a semiquantitative manner. Chi-square test was used for statistical analysis. RESULTS: MT overexpression was found in the fibroblasts of all ulcerative and/or fissural lesions in UC and CD. MT overexpression in intestinal epithelial cells of 40% of UC and CD lesions correlated significantly with the grade of inflammation. CONCLUSIONS: MT-immunoreactivity in fibroblasts supports a protective role for MT in inflammatory bowel disease. It remains unclear whether MT overexpression in epithelial cells is also important in this protection.

Humans↗

Dose-dependent induction of transforming growth factor beta (TGF-beta) in the lung tissue of fibrosis-prone mice after thoracic irradiation.

PURPOSE: The lung is the major dose-limiting organ for radiotherapy of cancer in the thoracic region. The pathogenesis of radiation-induced lung injury at the molecular level is still unclear. Immediate cellular damage after irradiation is supposed to result in cytokine-mediated multicellular interactions with induction and progression of fibrotic tissue reactions. The purpose of this investigation was to evaluate the acute and long-term effects of radiation on the gene expression of transforming growth factor beta (TGF-beta) in a model of lung injury using fibrosis-sensitive C57BL/6 mice. METHODS AND MATERIALS: The thoraces of C57BL/6 mice were irradiated with 6 and 12 Gy, respectively. Treated and sham-irradiated control mice were sacrificed at times corresponding to the latent period (1, 3, 6, 12, 24, 48, 72 hours and 1 week postirradiation), the pneumonic phase (2, 4, 8, and 16 weeks postirradiation), and the beginning of the fibrotic phase (24 weeks postirradiation). The lung tissue from three different mice per dosage and time point was analyzed by a combination of polymerase chain reaction (PCR), immunohistochemistry, and light microscopy. The mRNA expression of TGF-beta was quantified by competitive reverse transcriptase/polymerase chain reaction (RT-PCR); the cellular origin of the TGF-beta protein was identified by immunohistochemical staining (alkaline phosphatase-anti-alkaline phosphatase [APAAP]). The cytokine expression on mRNA and protein level was correlated with the histopathological alterations. RESULTS: Following thoracic irradiation with a single dose of 12 Gy, radiation-induced TGF-beta release in lung tissue was appreciable already within the first hours (1, 3, and 6 hours postirradiation) and reached a significant increase after 12 hours; subsequently (48 hours, 72 hours, and 1 week postirradiation) the TGF-beta expression declined to basal levels. At the beginning of the pneumonic phase, irradiation-mediated stimulation of TGF-beta release reached maximal values at 2 and 4 weeks. The elevated levels of TGF-beta mRNA during the latent phase have been found to correlate with immunohistochemical staining of alveolar macrophages. The most striking increase in TGF-beta immunoreactivity was seen during the acute phase of pneumonitis. Throughout this observation period, type II pneumocytes and fibroblasts (apart from inflammatory cells) served as important sources of TGF-beta expression. Increased TGF-beta expression was detected prominently in regions of histopathologic radiation injury. After exposure to a single radiation dose of 6 Gy, the lung tissue revealed only a minor radiation-mediated TGF-beta mRNA response. The modest upregulation ranged from 6 hours to 48 hours after irradiation. Corresponding to the only minor histopathologic changes after thoracic irradiation with 6 Gy, measurement of TGF-beta mRNA levels during the later time points revealed no significant alterations in comparison to untreated control mice. CONCLUSIONS: This study demonstrates an acute and long-lasting increase in the expression of TGF-beta in lung tissue following thoracic irradiation with 12 Gy. The predominant localization of TGF-beta in areas of inflammatory cell infiltrates and fibrosis suggests involvement of this cytokine in the pathogenesis of radiation-induced pulmonal fibrosis. Further studies should be performed to explore the role of other cytokines in the development of radiation injury. An improved understanding of the underlying mechanisms of pulmonary fibrosis may eventually lead to modulatory intervention at the molecular level to modify the fibrotic process.

Animals↗

Potential embolization by atherosclerotic debris dislodged from aortic wall during cardiac catheterization:: histological and clinical findings in 7,621 patients.

Embolic events during cardiac catheterization have been attributed to atherosclerotic aortic debris dislodged by catheter manipulation. We evaluated the frequency and the histologic morphology of atherothrombotic material retrieved during placement of coronary catheters in patients undergoing diagnostic or interventional cardiac procedures. Over a 4-year period, macroscopically visible aortic debris from coronary catheters, if present after advancement to the ascending aorta, was obtained for histologic examination. In 41 of 7,621 patients (0.54%), visible atherothrombotic material was present in the backflow of catheters. Debris occurred most frequently with 8 Fr guiding catheters (98%). Histologic examination showed foam cells, cholesterol crystals, and amorphic lipoid substance as markers of atheromatous material from atherosclerotic plaques in 38/41 patients (93%) with former plaque hemorrhage in 55% of them. In three patients, fresh thrombus material was observed (7%). None of these patients showed in-hospital ischemic complications. Although visible atheromatous material is a rare phenomenon in cardiac catheterization, an increased risk of scraping debris is associated with large-lumen guiding catheters. In order to avoid vascular embolization, the use of smaller guiding catheters and sufficient free backflow of catheters after advancement are recommended.

Adult↗

Prognostic value of lymphocyte apoptosis in acute rejection of renal allografts.

BACKGROUND: Apoptosis is a cellular phenomenon generally found within rejecting transplants. It may play a role in physiological or therapy-associated deletion of infiltrating lymphocytes or in graft cell destruction. Our study focuses on apoptosis of infiltrating lymphocytes during acute kidney rejection after the initial steroid pulse therapy and on possible prognostic implications. METHODS: Renal biopsy specimens of 23 transplant recipients with acute tubulo-interstitial rejection were examined for appearance of apoptosis and compared with 11 transplant biopsies with unspecific organ injury accompanied by lymphocyte infiltration. In all patients, biopsies were performed after steroid pulse therapy, and, after confirmation of rejection, antilymphocytic antibody treatment was carried out. Apoptosis was determined via terminal deoxynucleotidyltransferase-mediated dUTP-digoxigenin nick end labeling analysis and confirmed by electron microscopy. RESULTS: Apoptosis of lymphocytes or of tubular epithelium was detected in 11 cases of acute rejection (48%), respectively. Four biopsies showed lymphocytic as well as tubular apoptosis, whereas five sections showed no signs of programmed cell death. In biopsies revealing unspecific injury, tubular cell apoptosis was more frequently found (73%) compared with lymphocyte apoptosis (27%, P<0.05). Most interestingly, patients with a beneficial recovery from acute rejection had a higher proportion of lymphocyte apoptosis compared with patients with poor rejection outcome. The Bcl-2 oncoprotein was widely found within infiltrating lymphocytes without counter-regulating apoptosis. CONCLUSIONS: Lymphocyte apoptosis is found as frequently as tubular cell apoptosis in rejecting renal grafts after steroid pulse therapy and might have prognostic value for rejection outcome.

Acute Disease↗

[Kikuchi-Fusimoto disease: the differential diagnosis of cervical lymphadenitis with recurrent attacks of fever].

HISTORY AND CLINICAL FINDINGS: A 49-year-old, otherwise healthy woman had recurrent fever and lymphadenopathy with leukopenia for nineteen years. Her symptoms prompted successless antibiotic therapy and extensive evaluations of fever of unknown origin. At admission there were several enlarged cervical lymph nodes and subfebrile temperatures. INVESTIGATIONS: Neither laboratory findings nor imaging did show an infectious, rheumatologic or hematologic cause of her symptoms. Histopathological examination of an lymph node biopsy revealed histiocytic, necrotizing lymphadenitis (Kikuchi-Fusimoto disease) as the underlying disease. TREATMENT AND COURSE: After spontaneous resolution without specific therapy the patient is now symptomless and well 9 months after diagnosis. CONCLUSION: Kikuchi-Fusimoto disease is a cause of benign and usually self-limiting lymphadenopathy. Clinicians and pathologists should be aware of this uncommon differential diagnosis since early histologic recognition will minimize potentially and unnecessary evaluations and treatments.

Biopsy↗

Murine leukocytes with ring-shaped nuclei include granulocytes, monocytes, and their precursors.

Leukocytes with ring-shaped nuclei (ring cells) are present in bone marrow (BM; approximately 50% of BM cells), in peripheral blood (PB), and in inflammatory infiltrates of mice, but also in humans during myeloproliferative disorders. They are usually referred to as polymorphonuclear cells (PMN), but we demonstrate that they additionally encompass different types of mononuclear (MNC)-like ring cells. PMN ring cells had constricted ring-shaped nuclei with a wide cytoplasmic center and were sorted among the GR-1high fraction. The MNC-like ring cells belonged to the GR-1low fraction. Their nuclei were not segmented and the cytoplasmic center of their nuclei was small. They were heterogeneous with one subgroup containing monocytes/macrophages according to ultrastructure, immunophenotype (BM8, F4/80, CD13, ER-HR3), activity of unspecific esterase, and phagocytosis of Leishmania major. A second subgroup contained myeloic precursor cells as they proliferated (Ki67), expressed ER-MP12, and showed on ultrastructure distribution patterns of peroxidase activity compatible with myelocytes, promyelocytes, or promonocytes. A third subgroup of cells had large, sometimes lobulated nuclei, was lineage marker(negative/low) (GR-1, Mac-1, B220 etc.), CD38-, but c-kit+ and sca-1+, and thus belonged to a close progeny of murine hematopoietic stem cells. In PB, ring cells encompassed mainly PMN, but also monocytes and cells with characteristics of both the granulocytic and monocytic lineage. Thus, ring cells comprise mature and precursor forms of myeloic cells. Their analysis revealed that in mice a clear distinction between the granulocytic and monocytic lineage beyond the GM-CFU stage is not always feasible.

Animals↗

Differential effects of angiotensin II receptor blockade on pressure-induced left ventricular hypertrophy and fibrosis in rats.

The effects of the angiotensin II receptor type 1 (AT1) antagonist losartan on pressure overload-induced left ventricular (LV) hypertrophy were studied in female Sprague-Dawley rats. Starting on the day of surgery, losartan (L, 12 mg/kg/day) was administered as continuous intraperitoneal infusion for 2 weeks by using alzet mini-osmotic-pumps (model 2002). This dose of losartan shifted the in vivo dose-response curve of the angiotensin II-induced elevation of left ventricular systolic pressure (LVSP) to the right. Pressure overload was achieved by placing a band around the aortic arch. This caused an aortic stenosis (AS) with an outer diameter of 1.0 mm. The hemodynamic effects were measured in the intact, anesthetized rats (n = 15). The hearts were excised, and the weights of the left (LV) and right ventricle (RV) were determined. Some of these hearts (n = 7) were perfused with collagenase to obtain isolated cardiac myocytes for the measurement of cell volume. Other hearts (n = 8) were examined for morphological changes. In the animals with AS, LVSP was markedly elevated. Furthermore, LV weight and LV myocyte cell volume were increased in this group, while RV weight and RV myocyte cell volume remained stable in all the groups. L had no significant effect on the AS-induced increase in LVSP and cell size parameters, nor on the weight gain of the LV. Histological analysis revealed that the AS-induced enlargement of the mean myocyte diameter was not affected by L. The interstitial collagen fraction was increased in the AS rats and became normalized by L. These data suggest that the renin-angiotensin system might not be involved in the development of pressure-induced cardiac hypertrophy within the time-frame of these experiments, but that it does play a major role in the genesis of the interstitial fibrosis which is a typical feature of this pathophysiological condition.

Angiotensin Receptor Antagonists↗

Transepithelial transport processes at the intestinal mucosa in inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) of unknown etiology. Oral absorption studies have shown an increased intestinal permeability for various sugar molecules in patients with IBD and their healthy relatives as a possible pathogenetic factor. However, the various transport pathways through the mucosal barrier have not yet been examined. This study therefore investigated whether antigens pass the epithelial barrier by a transcellular or a paracellular pathway. Mucosa of freshly resected specimens from CD (n = 10) or UC (n = 10) patients was investigated by immunoelectron microscopy and compared with healthy mucosa. Epithelial transport was studied with the antigens ovalbumin and horseradish peroxidase after defined incubation. Labeling density of subunit c of ATP synthetase was determined in mitochondria of enterocytes of all specimens. In all specimens epithelial transport of OVA and HRP was principally transcellular through enterocytes with normal ultrastructure, although some tight junctions in CD and UC were dilated. Antigens were transported within vesicles to the basolateral membrane 2.5 min after incubation. The level of enterocytes with electron-lucent cytoplasm containing a high amount of antigens was higher in CD and UC than in healthy mucosa, depending on the grade of inflammation. ATP synthetase was significantly decreased in electron-lucent cytoplasm of CD and UC to normal ultrastructure of healthy mucosa. Our study shows that ovalbumin and horseradish peroxidase taken up by the apical membrane reach the paracellular space by vesicular transport in healthy and IBD enterocytes within a few minutes. Transcellular pathway is affected in both CD and UC, which is indicated by a high level of antigens within the cytosol. We speculate that increased intestinal permeability in IBD results substantially from enhanced transcellular transport.

Adult↗