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Biomedical subjects

T Schaffner

Publications and source records attributed to T Schaffner.

At least 73 records · Page 4Linked to original sources

[Sudden death during mass running events in Switzerland 1978-1987: an epidemiologico-pathologic study].

Between 1984 and 1987 there were 7 cases of sudden cardiac death during organized mass runs in Switzerland, and between 1978 and 1987 there were 3 cases during the nine largest mass running events (total 8 cases of sudden death during the race). Based on numbers of participants in all events 1984-1987, or in the nine largest events 1978-1987, an incidence of 1 sudden death per 129,500 hrs. of running (95% confidence interval 1/62,500-1/263,000 hrs.), or 1 sudden death per 117,000 hrs. of running (1/45,000-1/311,000 hrs.) respectively, was estimated. This estimate is higher than the rate of 1 sudden death per 396,000 hrs. of noncompetitive jogging found in a study from the United States (Thompson et al.: J. Amer. med. Ass. 1982; 247: 2535-2538). The Swiss incidence of sudden cardiac death during organized mass runs was 50 to 1000 times higher than the incidence expected by chance alone (as estimated from national death register data). All 8 cases of the study were men, the younger four aged 23 yrs. on average (range 20-31 yrs.), the older four aged 49 yrs. (46-53 yrs.). Autopsy in three of the younger men identified hypertrophic cardiomyopathy in one instance whereas in the two other cases no plausible cause of death could be found. The two autopsies performed in older men both showed severe coronary heart disease. Only in 1 case out of the 8 were possible prodromal symptoms of the subsequent death, such as fatigue and nausea, observed, and the average prevalence of known cardiovascular risk factors was low. None of the 8 runners dying suddenly was completely untrained, but 6 out of 8 had only modest running experience, i.e. a low number of years of running. This study confirms that there is probably a clearly increased risk of sudden death during running events with a competitive character, but this acute elevation of risk should probably not be overstated in view of both its very low population - attributable risk and the important potential of regular exercise for overall coronary risk reduction and health promotion.

Adult↗

Neuropathology of the acquired immune deficiency syndrome (AIDS): a report of 135 consecutive autopsy cases from Switzerland.

Neuropathological changes were studied in a consecutive autopsy series of 135 cases, comprising 73% of all patients who died of AIDS in Switzerland between April 1981 and December 1987. Central nervous system involvement was found in 119 patients (88%), 19 of which had multiple concomitant intracerebral lesions. Among the non-viral opportunistic infections, encephalitis due to Toxoplasma gondii was most frequent and occurred in 35 patients (26%), followed by central nervous system infection with Cryptococcus neoformans, which was found in five patients (4%). Cytomegalovirus (CMV) encephalitis was present in 14 patients (10%). Disseminated microglial nodules without morphological or immunocytochemical evidence of CMV was encountered in 18 patients (13%). However, in all but two of these patients there was evidence of extracerebral CMV infection, suggesting that CMV was responsible for these nodular encephalitides. Nine patients (7%) had progressive multifocal leukoencephalopathy (PML); in five of these, demyelination was associated with extensive tissue destruction and cyst formation. HIV-associated encephalopathy was observed in 21 patients (16%) and showed two characteristic morphological patterns: progressive diffuse leukoencephalopathy (PDL) and multifocal giant cell encephalitis (MGCE). PDL was observed in 13 cases and characterized by diffuse pallor and gliosis of the cerebral and cerebellar white matter with scattered multinucleated giant cells, but without significant inflammatory response. MGCE was found in eight patients and characterized by clusters of numerous multinucleated giant cells, rod cells, macrophages, lymphocytic infiltrates and occasional necroses. In our view, PDL and MGCE represent the two opposite variants of HIV-induced encephalopathies, with overlapping intermediate manifestations.

Acquired Immunodeficiency Syndrome↗

Heterogeneous malignant non Hodgkin's lymphomas as a causative disorder in lethal midline granuloma.

The present report describes the results of a combined morphological, enzyme- and immunohistochemical analysis of nine cases of malignant non Hodgkin's lymphomas (NHL) clinically presenting as lethal midline granuloma. In a previous report written before antibodies directed against B and T lymphocytes were available, a histiocytic origin of such neoplasms had been suggested. A panel of antibodies reactive with most B cells (L26, MB1, KiB3) and a majority of T cells (MT1, UCHL1) was applied on paraffin sections of formalin fixed tissues as well as antibodies directed against leukocyte common antigen (LCA), myeloid/histiocyte antigen (MAC 387), lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, S-100 protein, prekeratin and immunoglobulin light chains. Enzyme histochemistry included tests for non-specific acid esterase, acid phosphatase, beta-glucuronidase and chloroacetate esterase. As a result, five T, two B and two unclassified (malignant histiocytosis probable) NHL were identified, indicating distinct heterogeneity of NHL as causative disorders in lethal midline granuloma.

Adolescent↗

Participation of mitochondrial proliferation in morphological differentiation of murine mastocytoma cells.

Proliferation of a cold-sensitive cell-cycle mutant isolated from an undifferentiated murine mastocytoma line is reversibly arrested at the nonpermissive temperature of 33 degrees C, and the arrested cells undergo morphological differentiation as expressed by the formation of metachromatic granules. Following transfer of these mutant cells from the permissive temperature of 39.5 to 33 degrees C, a transient increase in both cytochrome c oxidase and DNA polymerase gamma was observed, the ratio of total mitochondrial volume to cell volume nearly doubled within 6 days, and numbers of mitochondrial cross-sections per cellular cross-section as determined in electron micrographs underwent a threefold increase. Addition of chloramphenicol (100 micrograms/ml) to the mutant cell cultures 6 days prior to transfer from 39.5 to 33 degrees C prevented the increase in the ratio of total mitochondrial to cell volume. Furthermore, chloramphenicol markedly inhibited the increase in granule number per cell that normally is observed after transfer of cultures to 33 degrees C or during treatment with 1 mM butyrate, suggesting that mitochondrial proliferation may be an obligatory step in the process of morphological differentiation of these mastocytoma cells.

Animals↗

Hormonotherapy of meningiomas with medroxyprogesterone acetate. Immunohistochemical demonstration of the effect of medroxyprogesterone acetate on growth fractions of meningioma cells using the monoclonal antibody Ki-67.

The effect of medroxyprogesterone acetate (MPA) on growth fractions of ex vivo meningiomas is demonstrated in using the Ki-67 monoclonal antibody in three cases of meningiomas operated on in two stages and in meningioma specimens from a group of eight patients operated on in one single stage after MPA therapy. Growth fractions in samples from five meningioma patients not treated with MPA were determined for comparison. In the three cases of two-stage operation of the tumors, the percentage of Ki-67-positive cells in meningioma tissue was lower by a factor of 6, 5, and 3, respectively, after MPA therapy. In meningioma specimens from patients receiving no MPA therapy, Ki-67-positive cells were present in 1.02 +/- 0.48%; in samples from MPA-treated tumors the percentage of Ki-67-positive cells was 0.41 +/- 0.40 (different at p less than 0.02 [Wilcoxon's test]). In comparison to our previously published data on untreated meningiomas analyzed for progesterone receptors (PR), MPA significantly reduced the PR activity. There was no obvious correlation between PR activity and potential suppression of the tumor growth fraction. It is concluded that MPA is attractive because it reduces the growth fractions of most meningiomas and might be suitable for adjuvant hormonotherapy.

Antibodies, Monoclonal↗

In vitro susceptibility of fungi to killing by neutrophil granulocytes discriminates between primary pathogenicity and opportunism.

Pathogenic fungi, according to their propensity to cause infection of apparently normal individuals, can be grouped into either primary pathogens (e.g., Coccidioides, Histoplasma, Paracoccidioides, Blastomyces, and Sporothrix) or opportunists (e.g., Candida, Mucoraceae, Aspergillus spp., Petriellidium, and Trichosporon). There is, however, no unifying concept explaining the difference between the virulence of the two fungal categories. Previously we have speculated that neutrophils are the common denominator of the high natural resistance to opportunistic fungi. Accordingly, we then compared the susceptibility to killing by neutrophil granulocytes of Histoplasma, Blastomyces, Paracoccidioides, and Sporothrix with that of 14 opportunistic fungi. We found the four virulent dimorphic yeasts, in contrast to opportunistic fungi, to be resistant to killing by neutrophils. Virulent dimorphic yeasts were ingested by neutrophils, and triggered a respiratory burst comparably to opportunists but were less susceptible to hydrogen peroxide, suggesting that differences in the susceptibility to microbicidal products of leukocytes may explain the difference in virulence.

Blastomycosis↗

Thymic lymphopoiesis: protected from, or influenced by, external stimulation?

The mechanisms regulating thymic lymphopoiesis are still a matter of debate. Intracortical proliferation and differentiation of thymocytes are thought to be controlled by locally produced humoral factors and close contact with epithelial, possibly also phagocytic, cells, and restricted by products of the major histocompatibility complex. The observation of a translocation of intraabdominally introduced PVP-coated silica particles (Percoll) via parathymic lymph vessels and through the thymic capsule into the cortical parenchyma demonstrates that the thymic cortex is accessible to materials carried with the transcapsular flux of interstitial fluid, and that this barrier is less effective than the blood-thymus barrier. The proliferative activity of cortical thymocytes following an intraabdominal injection of particulate tetanus toxoid was compared in sites adjacent to, and distant from, parathymic lymph nodes. Absolute numbers of DNA-synthesizing thymocytes were found to be much higher in cortical areas close to the lymph nodes, where lymphatic vessels are most numerous, than on the opposite sides of the thymic lobes. Taken together, these findings indicate that--in addition to intrinsic control mechanisms--cortical thymocyte production may be influenced by peripheral stimulation to some extent, and that materials from sites which are drained by parathymic lymph nodes may be important in this respect.

Animals↗

Factor VIII-related antigen in malignant hemangioendothelioma of the thyroid: additional evidence for the endothelial origin of this tumor.

Malignant hemangioendothelioma of the thyroid gland, which most often originates in a hemorrhagic nodule, is a well-known entity in European alpine regions with endemic goiter. In other parts of the world it very rarely has been diagnosed. This tumor may display considerable morphologic variation and often has been interpreted as a variant of undifferentiated carcinoma. In 13 out of 20 thyroid tumors, classified by light microscopy as malignant hemangioendothelioma, Factor VIII-related antigen, a marker for endothelial cells, was demonstrated in neoplastic cells with the help of immunohistochemical technics applied to conventional paraffin sections. In one case, in which material suitable for electron microscopy was available, Weibel-Palade bodies were found in tumor cells. These findings add strong support to the notion of an endothelial origin of this neoplasm.

Aged↗

Immunohistochemical localization of apolipoprotein B in human atherosclerotic lesions.

A peroxidase-antiperoxidase immunohistochemical method was used to detect the presence of intracellular and extracellular apolipoprotein B (apo B) in paraffin sections of human abdominal aortas and coronary arteries with and without atherosclerotic involvement. The four aortas studied disclosed both intracellular and extracellular apo B in areas in which lipid was found by oil red O staining. Coronary arteries also demonstrated abundant extracellular apo B but failed to disclose intracellular apo B in cells with stainable lipid. Immunohistochemical detection of intracellular apo B in raised aortic lesions but not in cells of coronary lesions suggests that arteries that contain detectable amounts of intracellular apo B correspond to arteries that usually have earlier atherosclerotic involvement.

Adult↗

Impaired neutrophil locomotion associated with hyperadhesiveness in a patient with Chédiak-Higashi syndrome.

Neutrophils from a patient with Chédiak-Higashi (CH) syndrome exhibited defective directional locomotion in a gradient of activated plasma. Further analysis of the nature of this defect showed that CH neutrophils could respond normally to stimulation with f-Met-Leu-Phe, by increasing both their motility and polarization, provided the cells were kept in suspension. Contact with the substratum resulted in the loss of both motility and polarity in the majority of cells. CH neutrophils, in contrast to normal cells, did not respond chemokinetically to f-Met-Leu-Phe. Unstimulated random locomotion of CH neutrophils was also depressed, and this correlated with increased spreading on the substratum. Our results indicate that motility, locomotion and polarisation of CH neutrophils on the substratum are depressed because of excessive adhesion.

Cell Adhesion↗

Uptake by enterocytes and subsequent translocation to internal organs, eg, the thymus, of Percoll microspheres administered per os to suckling mice.

The translocation of Percoll microspheres (mean diameter 20-30 nm) from the intestinal lumen through the epithelial layer to internal organs was examined in suckling mice using transmission electron microscopy. Repeated administration of this material by gavaging for 7 consecutive days resulted in a heavy particle load of vacuolated enterocytes. A limited amount of Percoll was transported to the subepithelial tissue of both the villous mucosa and Peyer's patches where microspheres were found endocytosed, predominantly by macrophages. Even smaller numbers of particles reached mesenteric lymph nodes and, occasionally, milky spots of the omentum. Minor Percoll aggregates were easily found in Kupffer cells of the liver, indicating hematogenous translocation. Small numbers of particles were regularly detected in perivascular macrophages of the thymic cortex, which are in close contact with surrounding lymphocytes. We conclude that the thymic cortex is not totally inaccessible to particulate matter of the intestinal content.

Animals↗

Macrophage functions in antimicrobial defense.

In the present short review article, we discuss some recent findings regarding the role of macrophages in antimicrobial defense. Problems that are briefly considered include the production of monocytes and its modification in infectious diseases; the role of circulating monocytes and "fixed" macrophages in the blood stream; emigration of monocytes from the vascular bed and their accumulation at sites of microbial attack; role of macrophages in immune responses; stimulation and activation of these cells including secretory functions; attachment to their surface and phagocytosis of microorganisms; microbicidal activities of macrophages; their role in granuloma formation; inherited and acquired deficiencies of macrophage functions. Emphasis is placed on currently unresolved problems.

Animals↗

[Arterial lesions in childhood: possible precursors of atherosclerosis].

The mini-review on pathogenesis and possible etiologies of human atherosclerosis puts its emphasis on the arterial lesions preceeding clinically manifest atheroma-formation. These lesions which arise from childhood onwards may be caused by a variety of factors such as mechanical stress, immune complexes, infection, toxic products and hyperlipemia.

Age Factors↗

Immunophagocytic properties of retinal pigment epithelium cells.

Retinal pigment cells were dislodged from normal monkey eyes and incubated in glass-slide chambers. All viable pigment cells adhered strongly to glass. They demonstrated surface receptors for the Fc portion of immunoglobulin G and for the third component of complement by selectively binding and phagocytizing antibody or complement-coated erythrocytes. These phagocytic cells with receptors were identified as retinal pigment cells by characteristic ultrastructural features. Thus, retinal pigment cells, which are generally believed to be derived from neural tissue, are not only scavengers of photoreceptor cell debris, but also have surface receptors and phagocytic functions that may be important in ocular defense.

Animals↗

Arterial foam cells with distinctive immunomorphologic and histochemical features of macrophages.

A variable population of fat-filled "foam" cells in diet-induced experimental arterial intimal plaques of rabbits and monkeys were analyzed for several features characteristic of macrophages. These included: 1) surface binding and phagocytosis of antibody-coated or complement-coated erythrocytes to detect specific surface receptors; 2) cytochemical tests and ultrastructural features to evaluate cell function and structure; and 3) rapid adherence to glass, a feature of macrophage activity, to isolate and identify a homogeneous population of fat-filled foam cells from excised and disrupted arterial lesions. Mixed populations of cells grown in culture from explants of lesions were also analyzed and lipid-filled cells were studied in histologic sections of adjacent lesions. Eighty to ninety percent of the easily dislodged glass-adherent cells from lesions had surface receptors for the Fc portion of immunoglobulin G and for the third component of complement. Coated red blood cells were readily phagocytized, but noncoated cells were not. Acid lipase activity was demonstrated in the Fc-receptor-positive cells. These cells were also devoid of ultrastructural features of smooth muscle. Among the cells growing or migrating out of explants, a population of large round foam cells possessed all of the macrophage features found in the glass-adherent cells from lesions and lacked ultrastructural characteristics of smooth muscle. Fusiform lipid vacuolated cells also grew out of the explants but did not exhibit surface receptors, failed to phagocytize coated or noncoated erythrocytes and did not stain for acid lipase activity; these cells showed distinctive morphologic features of smooth muscle. In histologic sections of nearby lesions foam cells that showed macrophage characteristics, ie, acid lipase activity and the presence of lysozymelike antigen, lacked ultrastructural smooth muscle features. Smooth muscle cells in lesion sections often contained lipid but demonstrated no lysozyme or acid lipase activity. The occurrence of a population of cells with several functional and structural features of macrophages among the lipid-laden cells of experimental diet-induced arterial lesions suggests that some foam cells may be derived from monocytes. An alternative explanation, that metabolically altered autochthonous arterial wall cells assume one or more characteristics of mononuclear phagocytes is less likely, since some of the markers used in these experiments are unrelated. Both explanations deserve further careful study.

Animals↗