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Biomedical subjects

T Schaffner

Publications and source records attributed to T Schaffner.

At least 55 records · Page 3Linked to original sources
PubMed1993

Experimental assessment of thrombogenicity in vascular prostheses before and during prostaglandin E1 treatment.

The effect of prostaglandin E1 (PGE1; Prostavasin), a powerful platelet blocking agent, was assessed on various new synthetic or biological prostheses in a 6-min in vivo extra corporal arterio-venous (AV) shunt. In eight anaesthetised and heparinised minipigs (weight 25.1 +/- 1.9 kg) the following materials were tested before and during PGE1 infusion (alprostadil-alpha-CD; 40 micrograms/50 ml NaCl/50 min or 0.8 microgram/min): PTFE, (Gore-tex, TW, 4 mm ID); Xenograft, Biologic (Solcograft, 5 mm ID), (non-porous) and Dacron (Atrium, 4 mm ID); polyurethane 1 (Braun-Melsungen, 4 mm ID); polyurethane 2 (S. Gogolewski, 4 mm ID), (porous). Technetium-labelled platelet deposition and blood flow were measured; morphology was assessed by scanning electron microscopy (SEM) and histology. Compared to control levels, PGE1 infusion had a significant systemic effect on mean arterial pressure required by the protocol (MAP 82.6 vs. 66.6 mm Hg; p < 0.001) and flow (173.6 vs. 134.8 mm/min; p < 0.001). Standardised platelet counts per area showed a marked overall decrease from 197 to 130 counts/min/mm2; NS). The morphological assessment by SEM showed a slight increase of surface cellular deposition (score: 6.7 vs. 8.3), the histology score being unchanged (3.9 vs. 3.7). Looking at deposition of platelets for each prosthesis, the porous materials showed a net improvement after PGE1 treatment as compared to non-porous materials. We conclude that PGE1 may be of benefit by reducing platelet deposition in synthetic porous vascular prostheses in the early phase.

Alprostadil↗
PubMed1993

Phenotype of Langerhans cells in human afferent skin lymph derived from allergic contact dermatitis.

By means of microsurgical lymph cannulation human skin lymph derived from the late phase of an elicitation reaction to diphenylcyclopropenone was sampled. Cells were isolated by centrifugation and then treated with mouse anti-CD1a monoclonal antibodies and sheep antimouse antibody-coated Dynabeads. Ultrastructural and immunocytochemical analyses revealed anti-CD1a/Dynabead-rosetted CD1a- and protein S-100-positive cells which did not express monocyte surface markers, but surface antigens such as HLA-DR, ICAM-1 and, in part, LFA-3. In comparison to freshly prepared human epidermal Langerhans cells (LC), a large fraction of these cells contained no or markedly fewer Birbeck granules and exhibited extensive ruffling of the surface. These data suggest that the phenotype of LC in skin lymph derived from the elicitation phase of allergic contact dermatitis is similar to LC cultured in vitro. In the functional concept of LC of our time, these cells correspond to the dendritic cells designated as "veiled".

Adult↗
PubMed1992

Prevention of cardiac allograft rejection by FK506 and rapamycin: assessment by histology and nuclear magnetic resonance.

We assessed the effect of FK506 and rapamycin (RPM) in a heterotopic abdominal rat heart transplant model using a major histocompatibility mismatch (DA to LEW). The end-point of our study was the histologic grading of rejection (Stanford) and 31P magnetic resonance spectroscopy (MRS) at 1 week after transplantation. Two dosages of FK506 (2.0 and 8.0 mg/kg per os daily) and RPM (1.5 and 6.0 mg/kg intraperitoneally daily) were compared in allografts without and with cyclosporine (12.5 mg/kg per os daily) treatment. The results show: Weak heartbeat and full rejection at day 5 in all untreated allografts; severe rejection in groups on a low dose of FK506 and RPM; mild rejection in both high dose groups comparable to the results of the hearts treated with cyclosporine; MRS does not allow differentiation between no or mild forms of rejection. Energy-rich phosphates are near normal in the high dosage immunosuppression groups but show a significant reduction in the low dosage groups. We conclude that all three tested drugs can reduce the degree of rejection from severe (untreated allografts) to mild if given in an adequate dosage. MRS correlates well with the degree of histologic rejection but permits only the diagnosis of moderate or severe rejection.

Animals↗
PubMed1992

Assessment of new immunosuppressive drugs in a rat cardiac allograft heterotopic model.

We assessed FK506 (FK) and rapamycin (RPM) in a heterotopic abdominal rat heart transplant model using a major histocompatibility mismatch (DA to LEW). The end point of our study was histologic grading of rejection (Billingham and working formulation) at 1 week. Two doses of FK (2.0 and 8.0 mg/kg p.o., q.d.) and RPM (1.5 and 6.0 mg/kg i.p., q.d.) were compared to allografts without and with ciclosporin (12.5 mg/kg p.o., q.d.) treatment. Results show: (1) weak heartbeat and full rejection on day 5 in all untreated allografts; (2) weak heartbeat and high degree of rejection in groups receiving low doses of FK and RPM; (3) strong heartbeat and mild rejection in both high FK and RPM dose groups comparable to the results of the hearts treated with ciclosporin; (4) 1 animal in each high FK and RPM dose group showed possible signs of toxicity, and (5) the strength of the heartbeat was not a reliable indicator of the efficacy of an immunosuppressive drug. We conclude that even in a major histocompatibility mismatch model at the time of the strongest immune response (1 week), all three tested drugs can reduce the degree of rejection from severe (untreated allografts) to mild if given in an adequate dosage.

Animals↗
PubMed1992

Abuse of germanium associated with fatal lactic acidosis.

Germanium compounds are marketed as nonprescription drugs in Europe and are recommended by the suppliers for AIDS and metastatic cancer disease. We observed a patient with nonmetastatic breast cancer who died because of severe lactic acidosis (plasma lactate concentration = 27 mmol/l) after ingestion of 25 g of elemental germanium over a 2-months period. Renal failure and hepatotoxicity had newly developed during germanium intake. Postmortem examination revealed severe hydropic vacuolation of tubule cells and the presence of inclusion bodies predominantly in straight proximal tubule cells with normal appearance of renal interstitium and glomeruli. The liver showed panlobular steatosis. Urine, blood and tissue (kidney, liver, muscle, pancreas) levels of germanium were high. Lactic acidosis may have been caused by the combined, germanium-induced renal and hepatic failure (underutilization), but it remains to be seen whether germanium can affect lactate production and/or metabolism directly.

Acidosis↗
PubMed1991

Increased collagen around deformed finger nailfold capillaries in type I diabetes mellitus.

Quantitative finger nailfold capillary microscopy was performed in 25 patients with type I diabetes and in 27 healthy control subjects. In the last consecutive 6 patients and 7 controls of these populations, finger nailfold biopsies were taken. Measurements of loop width as an in vivo parameter for deformities of the capillary loops showed significantly higher values in diabetic patients than in controls. Histopathological examination showed markedly and significantly increased deposition of collagen in nailfold dermal papillae of the diabetic patients. The deposition of collagen was positively correlated with the number of capillary endothelial cells in the nailfold dermal papillae and with the size of the papillae in diabetic patients. It is concluded that, in addition to deformity of nailfold capillaries, collagen deposition may also be a sign of metabolic disturbance and perhaps of proliferation of capillary endothelial cells in diabetic microangiopathy.

Adult↗
PubMed1991

Differentiation of cardiac ischemia and rejection by nuclear magnetic spectroscopy.

Nuclear magnetic resonance (NMR) criteria of early cardiac rejection are similar to those seen in myocardial ischemia, that is, a reduction of high energy phosphatases (Pc; ATP) and an increase of inorganic phosphates (Pi). Our aim was to assess in vivo changes of phosphorous spectroscopy (31P) induced by cardiac rejection and myocardial ischemia in the same animal. Heterotopic heart isografts (n = 5) and untreated allografts (n = 5) were examined at seven days on a two tesla wide-bore magnet with a surface coil. Subtotal global ischemia was produced for sequential NMR measurements, followed by heart excision for histological rejection grading (Billingham). Results 1. Isograft served as controls and showed normal energy-rich phosphate compounds and pH. 2. Rejecting (moderate to severe) allografts showed a decrease of Pc/Pi and beta-ATP/Pi ratio compared with isografts. However no significant pH drop could be detected. 3. Induced ischemia was confirmed by marked ECG-ST elevation and showed a significant early global myocardial acidosis (pH less than 6.9) particularly in severe prolonged ischemia (p less than 0.05). 4. Using 31P NMR techniques, ischemically induced changes were similar in isografts and allografts with a trend towards a more pronounced extent in the latter groups. In conclusion, magnetic resonance spectroscopy (31P and pH) allows in vivo differentiation between cardiac rejection and acute myocardial ischemia.

Acute Disease↗
PubMed1991

[Hybrid prosthesis implant-supported superstructures in edentulous jaw. 1. Case planning].

Dental literature covers a wide range of implant-based denture supports. Based on static/dynamic as well as preventive periodontal considerations, rigidly anchoring the removable superconstruction of hybrid dentures using secondary splinting of four implants with telescope crowns or readymade cap-andpost systems, is generally appropriate in cases where the lower jaw is toothless. This makes possible an impeccable bridgeshaped design for the main part of the dentures, with wide-open inter-implant rincing areas. Clinical experience has shown that, in comparison to bridge dentures or rigid bridgework, secondary splinting in reconstructions greatly simplifies oral hygiene, particularly for elderly patients.

Aged↗
PubMed1991

[Hybrid prosthetic implant supported suprastructures in edentulous mandible. Conus crowns and shell-pin-systems on HA-Ti-implants. 2. Prosthetic construction principles].

Dental literature covers a wide range of implant-based denture supports. Based on static/dynamic as well as preventive periodontal considerations, rigidly anchoring the removable superconstruction of hybrid dentures using secondary splinting of four implants with telescope crowns or readymade cap-andpost systems, is generally appropriate in cases where the lower jaw is toothless. This makes possible an impeccable bridge-shaped design for the main part of the dentures, with wide-open inter-implant rincing areas. Clinical experience has shown that, in comparison to bridge dentures or rigid bridgework, secondary splinting in reconstructions greatly simplifies oral hygiene, particulary for elderly patients.

Crowns↗
PubMed1990

[Nervous system pathology in AIDS: results of a collaborative autopsy study from Switzerland].

Neuropathological lesions were studied in a consecutive autopsy series of 206 cases, comprising 61% of all patients who died of Aids in Switzerland between April 1981 and December 1988. Central nervous system involvement was found in 84% of the patients, and 17% showed multiple concomitant intracerebral lesions. Among the non-viral opportunistic infections, cerebral toxoplasmosis was most frequent (24%), whilst among the viral opportunistic infections, cytomegalovirus (CMV) encephalitis was most frequent (7%). A nodular encephalitis consisting of disseminated microglial nodules without morphological or immunocytochemical evidence of CMV occurred in 13.5% of the patients. The majority of these cases showed evidence of extracerebral CMV infection. Progressive multifocal leukoencephalopathy (PML) was observed in 6% of the patients and was associated with widespread tissue destruction and cyst formation. HIV encephalopathy occurred in 38 patients (18%) and showed two characteristic morphological patterns: progressive diffuse leukoencephalopathy (PDL) and multifocal giant cell encephalitis (MGCE). PDL was observed in 22 patients and was characterized by a diffuse demyelination and gliosis of the white matter with little inflammatory infiltrates and scattered multinucleated giant cells which were immunoreactive to HIV antigens. MGCE was found in 16 patients and was characterized by clusters of macrophages, lymphocytes, and HIV-immunoreactive multi-nucleated giant cells. In our view, PDL and MGCE represent two opposite variants of HIV-induced encephalopathies with numerous intermediate manifestations.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Pharmacokinetics and chronic toxicity of cyclosporine A in genetic hydroxylation-deficient dark Agouti rats.

Since oxidation plays a key role in the metabolism of cyclosporine A (CsA), the pharmacokinetics and the toxicity of CsA was investigated in female dark Agouti rats exhibiting a deficiency for debrisoquine hydroxylation and for dextromethorphan demethylation. When compared with Wistar rats (n = 10), dark Agouti rats (n = 10) had a higher mean clearance (4.8 ml/min per kg vs. 3.3 ml/min per kg) and a lower mean residence time (606 min vs. 1361 min) after intravenous dosing of CsA. The systemic availability of subcutaneous CsA was close to 100%. The steady state CsA concentrations assessed by HPLC in whole blood after subcutaneous dosing of 20 mg/kg per day for 23 days (n = 10) were about 1000 ng/ml in dark Agouti rats. When compared with dark Agouti rats treated with cremophore (n = 10) or not treated at all (n = 12), dark Agouti rats on chronic subcutaneous CsA plus cremophore for 23 days (n = 10) had no difference in kidney histology but had slightly increased liver fatty changes. Rats on CsA and/or cremophore had a decreased uric acid clearance and evidence of hypoaldosteronism. The urinary ratio of debrisoquine/4-hydroxydebrisoquine decreased in rats on CsA, whereas the O-demethylation and N-demethylation of liver obtained from rats on cremophore was impaired. Thus, dark Agouti rats show no difference in the metabolism of CsA and when given CsA for 23 days show drug-induced functional but no relevant structural light microscopic changes in the kidney, and functional and slight structural changes in the liver.

Animals↗
PubMed1990

Effect of hyperlipidemic serum and irradiation on wound healing in primary quiescent cultures of vascular cells.

After 8 weeks in culture, outgrowths from explants of aortic media of rhesus monkeys and New Zealand rabbits result in circular colonies of mature smooth muscle cells, quiescent in 10% serum. Such cultures were wounded by cutting out a 1.5-mm-wide strip. Migration of cells into the wound area was measured daily, and proliferation was assessed by [3H]thymidine incorporation. Migration began within 24 hr and at 7 days the defect was filled by proliferates of migrated cells. The cumulative labeling index was highest in the cells in the wound gap but was also increased in the remaining part of the culture. Wounding thus stimulated the uninjured portion of these primary cultures to proliferate, while in subcultures of these cells increase in [3H]thymidine incorporation was confined to the wound area. While hyperlipidemic serum has been shown to induce proliferation in unwounded cultures, it did not enhance cell replication elicited by wounding but reduced cell density and labeling index in the wound gap. Irradiation prior to wounding reduced cell proliferation to control values, while migration of cells was not significantly affected. In irradiated cultures, the inhibitory action of hyperlipidemic serum on cell migration became evident. Such quiescent cultures thus allow us to separate the effects of a specific injury on the proliferative and migratory responses of vascular smooth muscle.

Animals↗
PubMed1990

[Immunohistochemical differentiation of periretinal membranes].

The etiology of periretinal membranes, a complication of various ocular diseases, trauma, and ocular surgery, is still unknown. In the study reported here, 134 surgically removed periretinal membranes were semiquantitatively analyzed by immunohistochemical and morphological method (antigens S 100, GFAP, leukocyte antigens, factor 8; fibrosis). It was found that the cell population of the membranes varied both morphologically and immunohistochemically according to the disease. However, the RPE cell count did not correlate with the number of retinal tears recorded in the patients' histories.

Diabetic Retinopathy↗
PubMed1990

[Evaluation of recent vascular prostheses in the arteriovenous shunt].

Prosthetic vascular replacement materials are still suboptimal especially for distal peripheral and coronary bypass grafts due to the small caliber and high occlusion rates. Therefore new vascular grafts have been assessed with respect to blood compatibility, thrombogenicity and host pretreatment. In 12 heparinized minipigs (25 kg), a total of 120 small caliber grafts (i.d. 3.0 mm) were perfused (6 min) in a femoro-femoral arteriovenous shunt (AVS). Materials included: Dacron (Atrium), PTFE (Gore), Polyurethanes (PU), Auto- and Xenografts. Animals were treated preoperatively with fishoil (3 g EPA/QD x 3 weeks = group I), perioperatively with prostaglandins (PGE1 = group II) or with fishoil and graft incubation in plasma proteins (= group III) and compared to controls without pretreatment (= group 0). We measured flow, deposition of marked thrombocytes (HMPAO-Tc* per area and per weight). - Blood flow was similar in AVS for all groups and materials (168 +/- 86 ml/min, p = NS). There was no significant correlation in deposition of marked thrombocytes and host pretreatments (group 0: controls = 7356 counts/area, group I: fishoil = 6807. group II: PGE1 = 7864). However graft incubation in plasma proteins significantly lowered deposition of marked thrombocytes (1766 in group III vs. 7356 in group 0: p less than 0.05). And significant differences of thrombocyte counts where found between the different materials: Autografts less than PTFE less than Xenografts less than Small Pore PU less than Dacron less than Large Pore PU.--AVS is a useful tool to determine early thrombogenicity in prosthetic vascular replacement materials and to assess the effect of different host pretreatments.

Animals↗
PubMed1989

[Current concepts of the pathogenesis of atherosclerosis].

Rupture of plaques followed by thrombosis and thrombo- or atheroembolism mark the clinical horizon of ischemic organ lesions in atherosclerosis. Initiation and development of lesions precede these often dramatic events by decades. Precursor lesions arise within the first, irreversible ones may develop from the second decade of life onwards. Two concurring or succeeding pathogenetic mechanisms dominate: 1. Discrete or functional endothelial injury (in conjunction with hemodynamic wall stresses and effects of endogenous or exogenous toxic factors such as hormones, immune- and other mediators, components of tobacco smoke, etc.) induces increased flow of low density lipoprotein (LDL) into arterial tissue. Immigrating monocytes capture LDL and accumulate its cholesterol as ester droplets becoming foam cells. Net flux and accumulation of cholesterol probably correlate with plasmatic LDL-cholesterol levels. 2. Endothelial denudation, also occurring under the influence of mechanical wall stresses and in particular over precursor lesions, incites platelet aggregation and clotting mechanisms. As a consequence, arterial smooth muscle proliferates in the sense of repair of injury, resulting in the formation of scar tissue. Lipid-rich lesions with scanty scars seem to be particularly prone to rupture and thus important complications. Plaque rupture is probably the most common complication leading to ischemic disease, whereby the extent of formation and organisation of thrombi might determine whether infarction or chronic ischemia is the outcome.

Adult↗