Search PubMed⌕ Search

Biomedical subjects

G Schuler

Publications and source records attributed to G Schuler.

At least 271 records · Page 15Linked to original sources
PubMed1989

[Glucose tolerance and electrolyte metabolism in nifedipine and nifedipine dihydroergotoxin treated healthy subjects].

The effects of three oral doses of nifedipine 20 mg or nifedipine 20 mg/dihydroergotoxin 2 mg (Pontuc, HN 85) during three subsequent days on an oral glucose load (100 g) were compared to placebo. Neither drug altered the glucose load or inhibited the secretion of insulin or C-peptide. The fall of serum potassium was also identical to controls. Basal plasma norepinephrine concentrations were lower following nifedipine/dihydroergotoxine than after nifedipine alone (2 p less than 0.05). A decrease of the serum sodium concentration by 2 mmol/l was observed with nifedipine but not with the combined drugs.

Adult↗
PubMed1988

Treatment of coronary heart disease by diet and exercise: fasting and diurnal lipoproteins.

The effects of a combined exercise and low-fat dietary regimen were studied in 11 patients with angiographically documented coronary heart disease (cholesterol 233 mg/dl, triglycerides 158 mg/dl) and 13 comparable patients (cholesterol 224 mg/dl, triglycerides 174 mg/dl) on usual care. During one year, fasting serum lipoproteins were lowered to "ideal" levels in the intervention group (cholesterol 191 mg/dl, triglycerides 100 mg/dl, LDL-cholesterol 121 mg/dl). There was no change of triglycerides and cholesterol on usual care while LDL-cholesterol rose significantly. Neither regimen had any effect on HDL-cholesterol. Diurnal triglycerides as a presumptive measure of IDL in the intervention group were diminished by 39%. The study demonstrates the feasibility of a diet and exercise regimen to normalize mildly elevated plasma lipid levels and thus to possibly affect the course of coronary heart disease without drugs.

Cholesterol↗
PubMed1988

Efficacy of intravenous prourokinase and a combination of prourokinase and urokinase in acute myocardial infarction.

Fifty-four patients with Q-wave acute myocardial infarction (AMI) were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (prourokinase). To determine the optimal treatment regimen, prourokinase was applied in 3 different ways: group I received a bolus of 7.5 mg and a subsequent infusion of 40.5 mg over 60 minutes. Patency of the infarct artery was observed in 7 patients (50%) at the end of the infusion time. One hour after the end of the infusion the fibrinogen level had decreased to 87 +/- 12% of the preinfusion level; the plasminogen and alpha-2 antiplasmin levels to 61 +/- 13% and 59 +/- 34%, respectively. In group II prourokinase was administered as a 7.5 mg bolus followed by 66.5 mg over 60 minutes. Eleven patients (55%) had patent infarct-related coronary arteries and fibrinogen, plasminogen and alpha-2 antiplasmin levels had decreased to 58 +/- 29%, 38 +/- 18% and 21 +/- 14%, respectively. Group III was treated with a bolus of 3.7 mg prourokinase and 250,000 IU urokinase followed by 44.3 mg prourokinase, resulting in a patency rate of 65% (13 patients). Fibrinogen, plasminogen and alpha-2 antiplasmin levels decreased to 76 +/- 15%, 67 +/- 15% and 47 +/- 29%, respectively. Fibrin-specific thrombolysis can be achieved with glycosylated prourokinase. At higher dosages considerable systemic activation of the fibrinolytic system with little enhancement of the observed therapeutic effect occurred. The combination of prourokinase and urokinase yielded a higher patency rate than either dosage of prourokinase alone, although the difference was not statistically significant in this pilot trial.

Clinical Trials as Topic↗
PubMed1988

IFN-mediated induction of MHC antigen expression on human keratinocytes and its influence on in vitro alloimmune responses.

The MHC Ag expression on the surface of keratinocytes is altered after treatment with IFN. IFN-gamma induces, as expected, a strong increase in class I MHC Ag expression as well as de novo expression of class II MHC Ag, whereas IFN-alpha 2 only slightly increases class I MHC Ag and does not induce keratinocytes to express class II MHC Ag. We used untreated and IFN-pretreated keratinocytes as stimulators and also as targets to study whether IFN-induced MHC Ag changes would alter the immunogenicity of keratinocytes in alloimmune responses. It was found that class II MHC Ag-carrying keratinocytes were unable to induce the proliferation of resting lymphocytes, but did stimulate T blasts. Untreated keratinocytes were virtually resistant to the lysis by classical CTL but became susceptible after exposure to IFN-gamma, but not IFN-alpha 2 at physiologic doses. These data demonstrate mechanisms by which the release of IFN-gamma might contribute to the development of disease such as the graft vs host disease.

Cell Division↗
PubMed1988

Granulocyte/macrophage colony-stimulating factor and interleukin 1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells.

Freshly isolated, murine epidermal Langerhans cells (LC) are weak accessory cells for primary T cell-dependent immune responses, but increase their stimulatory capacity at least 20-fold progressively over a 3-d culture with keratinocytes. We have studied the mediators of LC maturation. LC enriched from 12-h epidermal cultures by negative selection do not survive when cultured for 60 h in standard medium. LC survive and show increased stimulatory capacity for oxidative mitogenesis and the primary MLR when 30% keratinocyte-conditioned medium is included. Of the three cytokines that are known to be produced by keratinocytes, only granulocyte/macrophage CSF (GM-CSF) maintains viability and increases stimulatory capacity. IL-1 alone does not keep LC alive, but further enhances the stimulatory activity when combined with GM-CSF. IL-3 has no effect. The increase in LC stimulatory capacity is not due to increased Ia antigen expression, which does not change between 12 and 60 h. Function is not simply due to improved viability, as GM-CSF does not enhance the function of 12-h LC when added to the short-term oxidative mitogenesis assay. By generating LC with strong stimulating activity for resting T cells, GM-CSF and IL-1 may be critical in the sensitization phase of T cell-mediated immunity.

Animals↗
PubMed1988

What is established in thrombolytic therapy of acute myocardial infarction? Pharmacological approaches.

Thrombolytic therapy by early reopening of an occluded coronary vessel, and hence re-establishing oxygen delivery, can significantly reduce infarct size. The result depends both on the duration of ischemia and the presence of collaterals. By early initiation of intravenous thrombolytic therapy and shortening the ischemic period, the functional results may be improved. PTCA has to be considered in order to avoid reocclusion of the infarct vessel, mainly in patients with high-grade residual stenosis and viable myocardium in the poststenotic area. The benefit of early thrombolytic therapy in acute myocardial infarction has been proven in randomized trials. However, to achieve statistical significance, a large number of patients had to be included. It is mainly the patients with previous myocardial infarction with a large area at infarct risk and/or anterior myocardial infarction that derive most benefit from this intervention.

Acute Disease↗
PubMed1988

Myosin light chains release in acute myocardial infarction: non-invasive estimation of infarct size.

After the loss of membrane integrity cardiospecific myosin light chains are released as a result of proteolytic degradation of the insoluble myosin pool. Thus, as with cytosolic enzymes, the measurement of the serum concentration changes of myosin light chains may allow a non-invasive estimation of infarct size. A two compartment model was used to describe the serum concentration changes of myosin light chains after a bolus injection into awake beagle dogs. The initial distribution volume was 7.4% of body weight, whereas the second compartment accounted for 4.7% of body weight. The fractional disappearance rate of 0.0092.min-1 resulted in a serum half life of myosin light chains of 75 min. In 30 patients with acute non-reperfused myocardial infarction a close correlation was found between the cumulative appearance of myosin light chains and their maximal serum concentration. In these patients the cumulative appearance of myosin light chains correlated with serum creatine kinase estimates of infarct size, with impairment of left ventricular ejection fraction, and with mortality during hospital admission. Thus the maximal serum concentration and the cumulative appearance of myosin light chains allow a non-invasive estimation of infarct size and may serve as a serological indicator of the patient's prognosis.

Adult↗
PubMed1988

Monoclonal antibodies specific for human cardiac myosin: selection, characterization and experimental myocardial infarct imaging.

Radiolabelled anti-myosin antibodies (AM Ab) specifically accumulate in necrotizing myocytes and, therefore, allow the scintigraphic detection of myocardial infarction. In order to provide a constant supply of myosin-specific antibodies, the somatic cell fusion technique was used for the selection and propagation of AM Ab. Out of 126 antibody producing cell lines, nine were selected for further subcloning, due to their high affinity for purified myosin. For the in vivo imaging, two IgG-antibody molecules appeared particularly useful based on their antigenic specificity as assessed by immunoblotting and indirect immunofluorescence technique. After radiolabelling with iodine-123, undigested antibody molecules or their Fab fragments were injected into 10 dogs with experimental myocardial infarction. The accumulation of radioactivity in myocardial infarction was assessed by in vivo imaging and in vitro scintigraphy of ventricular slices stained by tetrazolium. The use of undigested AM Ab resulted in a high uptake ratio of radioactivity in the infarcted as compared to normal myocardium (20:1). In vivo infarct imaging, however, was not possible due to sustained labelling of the blood pool. The uptake ratio of iodine-123 labelled Fab fragments was only 9:1, but due to a faster plasma clearance of the Fab fragments, uptake in the heart could be visualized 5 h after intravenous injection. Clear differentiation between infarcted and noninfarcted myocardium, however, was limited by accumulation of radioactivity in the thoracotomy wound, in the liver, and in the stomach.

Animals↗
PubMed1988

Rejection, after a slightly prolonged survival time, of Langerhans cell-free allogeneic cultured epidermis used for wound coverage in humans.

Autologous cultured epidermis (CE) grown from small skin biopsies in vitro has been successfully applied for wound grafting in humans. Since it has been reported recently that allogeneic CE might be tolerated as permanent wound cover, we investigated the properties of CE and its use as autologous and allogeneic grafts. Except for some differences, such as the absence of Langerhans cells and the lack of a stratum corneum, CE resembled its natural analogue. Autologous CE applied for grafting of leg ulcers and various surgical skin defects adhered firmly and permanently to the wound bed within 2 weeks, became regularly stratified, and formed a stratum corneum. Langerhans cells gradually entered the grafts; the dermis contained no inflammatory infiltrate. Allogeneic CE unmatched for MHC and blood group antigens used to partially cover tangentially excised third-degree burns, donor sites of split-thickness skin, and a defect after tumor excision initially survived well like the autografts. However, they were completely rejected after 10-22 (mean, 14.5) days, which is 4-5 days later than reported for split-thickness skin allografts. Clinically, rejection presented as "melting" of the graft. (Immuno)histologically, we found a dense mononuclear dermal infiltrate consisting predominantly of activated T cells, vacuolization, and single-cell necrosis of keratinocytes, as well as HLA-DR expression on keratinocytes, and finally separation and lysis of the epidermis. Limiting dilution analysis in 2 out of 4 allograft recipients revealed a considerable increase of circulating donor-specific cytotoxic T cell precursors during graft rejection. We conclude that grafting of allogeneic CE does not lead to permanent but to slightly prolonged graft survival.

Adolescent↗
PubMed1988

Low-fat diet and regular, supervised physical exercise in patients with symptomatic coronary artery disease: reduction of stress-induced myocardial ischemia.

The effects of physical exercise and normalization of serum lipoproteins on stress-induced myocardial ischemia were studied in 18 patients with coronary artery disease, stable angina pectoris, and mild hypercholesterolemia (total serum cholesterol 242 +/- 32 mg/dl). These patients underwent a combined regimen of low-fat/low-cholesterol diet and regular, supervised physical exercise at high intensity for 12 months. At 1 year serum lipoproteins has been lowered to ideal levels (serum cholesterol 202 +/- 31 mg/dl, low-density lipoproteins 130 +/- 30 mg/dl, very low-density lipoproteins 22 +/- 15 mg/dl, serum triglycerides 105 [69 to 304] mg/dl) and physical work capacity was improved by 21% (p less than .01). No significant effect was noted on high-density lipoproteins, probably as a result of the low-fat/high-carbohydrate diet. Stress-induced myocardial ischemia, as assessed by thallium-201 scintigraphy, was decreased by 54% (p less than .05) despite higher myocardial oxygen consumption. Eighteen patients matched for age and severity of coronary artery disease served as a control group and "usual medical care" was rendered by their private physicians. No significant changes with respect to serum lipoproteins, physical work capacity, maximal rate-pressure product, or stress-induced myocardial ischemia were observed in this group. These data indicate that regular physical exercise at high intensity, lowered body weight, and normalization of serum lipoproteins may alleviate compromised myocardial perfusion during stress.

Body Weight↗
PubMed1988

[5-year survival rate in acute transmural heart infarct following thrombolysis and immediate coronary angioplasty].

Two-hundred-eighty-six patients with acute transmural myocardial infarction underwent thrombolytic treatment (Streptokinase) between 1980 and 1986. In the earlier years patients were treated by thrombolysis only (n = 158) and in more recent years by thrombolysis followed by immediate percutaneous transluminal coronary angioplasty (n = 128). Age, sex, incidence of previous infarction and incidence of multivessel disease were comparable between groups. Patency of the infarct vessel (TIMI 3) was higher after thrombolysis combined with angioplasty than after thrombolysis alone (87% vs. 70%, p less than 0.001), and the residual stenosis of the infarct vessel was lower (46% vs. 84%, p less than 0.05). Hospital mortality (thrombolysis combined with angioplasty vs. thrombolysis alone) was 6% vs. 13%; one-year mortality was 8% vs. 21%, and five-year mortality was 18% vs. 31% (p less than 0.02). We conclude that treatment of patients with acute transmural myocardial infarction by thrombolysis combined with angioplasty is followed by a better long-term prognosis than treatment by thrombolysis only.

Angioplasty, Balloon↗
PubMed1988

Metabolic effects of intravenous proinsulin.

Proinsulin induced hypoglycemia was characterized in eight healthy male volunteers. Proinsulin cleared slower from the circulation than insulin. The metabolic effects on plasma glucose, free fatty acids, glycerol, 3-hydroxybutyrate, potassium, and phosphate occurred slower. The anti-lipolytic effect of proinsulin was longer than that of insulin (2P less than 0.001). The hormonal responses of epinephrine, norepinephrine, prolactin, hGH, and cortisol were attenuated following proinsulin. The amount of epinephrine secreted during counterregulation and the amount of lactate produced in response to beta-stimulation were both correlated to the fall of plasma glucose (2P less than 0.005). Stress symptoms were milder after proinsulin (2P less than 0.01). The data obtained are consistent with the hypothesis that the slower kinetics of proinsulin cause slower metabolic effects. The assumption of non-insulin-like effects of a differing pattern of insulin-like effects is not necessitated by the results of this study.

3-Hydroxybutyric Acid↗
PubMed1988

[Painless aortic dissection: the problem of early diagnosis. A case report].

Painless aortic dissections occur very rarely, the absence of the important cardinal symptom "pain" may cause a delayed establishment of diagnosis. As early operation improves prognosis, this delay may have harmful consequences for the patient. The case reported presented initially only with neurological symptoms and later with blood pressure instabilities. Nevertheless, the diagnosis has been established within 48 h, but the patient did not survive operative emergency treatment.

Aged↗
PubMed1987

[Balloon dilatation in unstable angina pectoris and acute myocardial infarct].

Early results after percutaneous transluminal coronary angioplasty (PTCA) in patients with unstable angina or acute myocardial infarction were compared with those in patients with stable angina. The primary success rate in 115 patients with unstable angina was 72%, in 73 with acute myocardial infarction 78%, and in 213 with stable angina 79%, i.e. there was no difference between the three groups. In patients with acute myocardial infarction and primary successful PTCA control angiography was performed one month after PTCA, in patients with unstable and stable angina 6 months after PTCA. Angiographic findings were identical in the three groups. But the results after successful balloon dilatation were dependent on the extent of primary success: in all three groups, patients in whom the post-dilatation control angiography revealed recurrence of stenosis the primary results were worse than in those without. There was no difference between those patients with lasting success and those with recurrence as regards cholesterol level, arterial hypertension, diabetes, and smoking habits. It is concluded that in every patient with acute symptoms of coronary heart disease the indication for PTCA should be considered.

Angina Pectoris↗
PubMed1987

Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells.

A panning method has been developed to enrich Langerhans cells (LC) from murine epidermis. In standard culture media, the enriched populations progressively lose viability over a 3-d interval. When the cultures are supplemented with keratinocyte-conditioned medium, LC viability is improved and the cells increase in size and number of dendritic processes. Accessory function, as monitored by stimulating activity in the mixed lymphocyte reaction (MLR), increases at least 10-20-fold. The conditioned media of stimulated macrophages and T cells also support the viability and maturation of cultured LC. A panel of purified cytokines has been tested, and only granulocyte/macrophage colony-stimulating factor (GM-CSF) substitutes for bulk-conditioned medium. The recombinant molecule exhibits half-maximal activity at 5 pM. Without activity are: IL-1-4; IFN-alpha/beta/gamma; cachectin/TNF; M- and G-CSF. A rabbit anti-GM-CSF specifically neutralizes the capacity of keratinocyte-conditioned medium to generate active LC. However, GM-CSF is not required for LC function during the MLR itself. We conclude that the development of immunologically active LC in culture is mediated by GM-CSF. The observation that these dendritic cells do not respond to lineage-specific G- and M-CSFs suggests that LC represent a distinct myeloid differentiation pathway. Because GM-CSF can be made by nonimmune cells and can mediate the production of active dendritic cells, this cytokine provides a T-independent mechanism for enhancing the sensitization phase of cell-mediated immunity.

Animals↗
PubMed1987

Intervention in acute myocardial infarction.

The most critical substrate lacking in infarcting myocardium is oxygen and early reperfusion would appear to be the most promising approach to infarct reduction. The efficacy of thrombolytic therapy has been shown by an increase in the global ejection fraction assessed by angiography or gated blood pool techniques and also by a decrease of almost 50% in the radioisotope perfusion defect after 3 to 4 weeks. Functional results in a group of patients subdivided according to success of thrombolysis and plasma creatine kinase levels showed that, among patients with successful thrombolysis, those with the least ischemic damage had experienced shorter ischemic periods and had significantly more collateral vessels supplying the infarcting area. It is recommended that the ischemic period should not extend beyond 3 to 5 hours before therapy is begun. The combination of intravenous streptokinase followed by intracoronary streptokinase was found to lead to a significant shortening of the ischemic period when compared with intracoronary streptokinase alone. Reocclusion of the infarct vessel has been shown to occur in 10% to 30% of patients after successful reperfusion, especially in arteries with severe residual stenosis, but immediate revascularization carried out after reperfusion in such patients can bring about a substantial decrease in the 1 year mortality rate. Successful reperfusion showed particular benefit in patients with previous myocardial infarction in another area, in patients with large left ventricular perfusion defects and in patients with predominantly right ventricular infarction.

Angioplasty, Balloon↗
PubMed1987

[Thrombolysis in acute myocardial infarct. An improved long-term prognosis following balloon dilatation].

UNLABELLED: A systemic and intracoronary thrombolytic treatment was carried out in 217 patients with acute transmural myocardial infarction between March 1980 and March 1985. 141 patients were only treated with thrombolysis, and 76 were additionally treated by balloon dilation in the same session. Indications for additional balloon dilation were unsuccessful thrombolysis as well as a residual stenosis of more than 50% after primarily successful thrombolysis. Age, sex, proportion of patients with anterior and posterior wall infarction as well as with 1, 2 and 3-vessel disease did not significantly differ in the two groups. The result of therapy (complete reperfusion) was less after thrombolysis than after thrombolysis with balloon dilation (63% as compared to 88%, P less than 0.0003). The patients who were only treated with thrombolysis had a more unfavorable three-year actuarial survival than those in whom thrombolysis and balloon dilation were carried out (70% as compared to 90%, P less than 0.02). CONCLUSION: additional balloon dilation in thrombolytic treatment of acute transmural myocardial infarction improves the long-term prognosis.

Angioplasty, Balloon↗