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Biomedical subjects

P Kaufmann

Publications and source records attributed to P Kaufmann.

At least 19 recordsLinked to original sources

Reduced epicardial coronary vasodilator capacity in patients with left ventricular hypertrophy.

BACKGROUND: Enlargement of the epicardial coronary arteries occurs in left ventricular (LV) hypertrophy as an adaptation to the increased coronary blood flow. METHODS AND RESULTS: Vasodilator capacity of the epicardial coronary arteries was determined in 44 patients. The dose-response relation of intracoronary nitroglycerin was assessed in 14 patients (7 control subjects and 7 patients with aortic stenosis [study A]) using quantitative coronary angiography. In a second study (B), vasodilator capacity of the epicardial coronary arteries was determined in 15 control subjects and 15 patients with valvular heart disease. In study A, a curvilinear dose-response relation with maximal vasodilation after 90 micrograms intracoronary nitroglycerin was found in both control subjects and patients with aortic stenosis. Vasodilator capacity was reduced in those with aortic stenosis, although sensitivity to nitroglycerin was similar in both groups. In study B, coronary circumferential length at baseline was larger in those with LV hypertrophy (12.2 +/- 2.2 mm) than in control subjects (8.6 +/- 1.5 mm; P < .001); after 100 micrograms intracoronary nitroglycerin, it increased to 12.9 +/- 2.2 mm (6 +/- 5%) in those with LV hypertrophy and to 10.3 +/- 1.5 mm (21 +/- 8%; P < .001) in control subjects. An inverse relation between baseline circumferential length and its percent increase after nitroglycerin was found (r = -.71, P < .001). CONCLUSIONS: Vasodilator capacity of the epicardial coronary arteries is reduced in patients with LV hypertrophy, although sensitivity to nitroglycerin is normal. This may be due to a flow-mediated decrease in coronary vasomotor tone and/or the occurrence of vascular remodeling with an enlargement of the coronary arteries.

Adult

Angiotropic large cell lymphoma presenting as thrombotic microangiopathy (thrombotic thrombocytopenic purpura).

BACKGROUND: Angiotropic large cell lymphoma is a rare lymphoproliferative disorder that affects vessels of almost all organs. Therefore, many different signs and symptoms can be observed and may delay a rapid diagnosis in these patients. However, no association between angiotropic large-cell lymphoma and thrombotic microangiopathy (TMA) has been reported so far. METHODS: The case report describes a 69-year-old female Caucasian who presented with fever, neurologic symptoms, microangiopathic hemolytic anemia, thrombocytopenia, and hyaline thrombi within small vessels. TMA was diagnosed and intense treatment, including plasma exchange and corticosteroid therapy, was initiated. Nevertheless, the patient died 3 days after admission. A postmortem examination including immunohistochemistry and molecular studies was performed. RESULTS: Autopsy revealed angiotropic large cell lymphoma with tumor cell aggregates in small vessels of the brain, myocardium, lungs, liver, small and large intestines, mesenterium, kidneys, and lymph nodes. Immunohistochemical analysis of the tumor cells showed positive reactions with B-cell markers, but negative T-cell and epithelial cell markers. Molecular studies using polymerase chain reaction with primers for the rearranged immunoglobulin heavy chain and the T-cell receptor beta chain gene confirmed the diagnosis of a monoclonal B-cell disorder. CONCLUSION: TMA can occur in association with angiotropic large cell lymphoma and, furthermore, can be its sole clinical manifestation.

Aged

The monoclonal antibody GB 42--a useful marker for the differentiation of myofibroblasts.

The expression patterns of a variety of cytoskeletal antigens were studied in normal human tissues (placenta, umbilical cord, myometrium, colon, mammary gland, testis, skeletal muscle, myocardium) as well as in abnormal human tissues (palmar fibromatosis, fibrocystic disease of the mammary gland, mammary carcinoma). The immunohistochemical binding patterns of the monoclonal antibody GB 42 were compared to those of commercial antibodies directed against vimentin, desmin, smooth muscle myosin, pan actin, alpha-smooth muscle actin and gamma-smooth muscle actin. Methods applied comprised immunohistochemistry on cryostat sections and paraffin sections. Immunogold immunocytochemistry was performed on Lowicryl sections. The patterns of GB 42-binding were confirmed biochemically by SDS-PAGE and Western-blotting, and quantitative amino acid analysis. Our data suggest that the monoclonal antibody GB 42 recognizes an actin isoform which is identical to, or closely related to, gamma-smooth muscle actin. Unlike the commercially available antibody against gamma-smooth muscle actin, GB 42 does not cross-react with alpha-skeletal or alpha-cardiac actins. The GB 42-antigen is expressed in smooth muscle cells, myoepithelial cells and in later stages of differentiation of myofibroblasts, in all the tissues investigated. Throughout the development of smooth muscle cells and myofibroblasts, the appearance of the GB 42-antigen occurs after the expression of vimentin, desmin and alpha-smooth muscle actin, but prior to the expression of smooth muscle myosin. GB 42 is a reliable marker for higher stages of differentiation of smooth muscle cells and myofibroblasts.

Amino Acids

Coronary vasomotion during dynamic exercise: influence of intravenous and intracoronary nicardipine.

OBJECTIVES: Our aim was to evaluate the influence of a calcium channel blocking agent of the dihydropyridine group (nicardipine) on coronary vasomotion during dynamic exercise. BACKGROUND: Coronary vasomotion plays an important role in the pathophysiology of myocardial ischemia. METHODS: Twenty-nine patients with coronary artery disease were studied at rest and during bicycle exercise with the use of biplane quantitative coronary angiography. Twelve patients without pretreatment (group 1) served as control subjects. Seventeen patients (group 2) received nicardipine, either 0.2 mg by intracoronary injection (n = 9) or 2.5 mg intravenously (n = 8) before exercise. RESULTS: In the control group there was exercise-induced vasoconstriction (-29%, p < 0.001) of the stenotic segment but coronary vasodilation (+22%, p < 0.05) of the normal vessel segment. In group 2, nicardipine induced coronary vasodilation of both the normal (+16%, p < 0.001) and the stenotic vessel segment (+35%). During subsequent exercise there was some additional vasodilation of normal (+4%, p = NS) and stenotic arteries (+5%, p = NS). There was no difference between either intracoronary or intravenous nicardipine with regard to vasodilation. Application of sublingual nitroglycerin was associated with significant vasodilation of the normal vessel segment in groups 1 (+18%, p < 0.05) and 2 (+15%, p < 0.001). The stenotic vessels showed a significant increase in percent cross-sectional area after nitroglycerin in groups 1 (+12%, p = NS) and 2 (+51%, p < 0.001). Exertional angina pectoris occurred less frequently in group 2 (18%) than in group 1 (67% [p < 0.005 vs. group 2]); group 2 also had a smaller increase in mean pulmonary artery pressure (+14 vs. +21 mm Hg, p < 0.05). CONCLUSIONS: Exercise induces vasoconstriction of stenotic, but vasodilation of normal, coronary vessel segments. Intravenous and intracoronary nicardipine prevent vasoconstriction of stenotic coronary arteries during exercise and exert a significant anti-ischemic effect. The combination of two anti-ischemic drugs, nitroglycerin and nicardipine, has an additive effect on coronary vasomotion that is seen only in the stenotic vessel segment. Thus, the anti-ischemic action of nicardipine is mainly due to a primary effect on coronary vasomotor response rather than to secondary effects such as changes in loading conditions.

Aged

Transient reduction of autoantibodies against oxidized LDL in patients with acute myocardial infarction.

Fifteen consecutive patients (mean age 66 +/- 14, range 31-82) with an acute myocardial infarction (MI) suitable for thrombolytic therapy were included in this study. Autoantibodies against oxidized low-density lipoprotein (LDL) were determined by enzyme-linked immunosorbent assay (ELISA). Patients (n = 10) with marked elevation of the MB isoenzyme of creatinine kinase (CK-MB)-mass had significant decreases of oLDL-Ab during the acute phase, with a minimum after 8 h following the onset of thrombolytic therapy (within-group significance: p < .001; between groups: p = .01). Patients (n = 5) with CK-MB-mass values less than 70 ng/ml did not show this phenomenon. Furthermore, significant correlations existed between CK-MB-mass and oLDL-Ab after 6 and 8 h (n = 15; r = .72; p = .003) and the time of the highest CK-MB-mass values (after 12 h) and the time of the maximal decrease of oLDL-Ab (after 8 h) (r = .74; p = .003). Our observations provide further evidence for the release of free radicals and for increased lipid peroxidation during reperfusion after prolonged ischemia. The decrease of oLDL-Ab appears to be a marker for the severity of MI.

Adult

Elaboration of stem villous vessels in growth restricted pregnancies with abnormal umbilical artery Doppler waveforms.

OBJECTIVE: To assess the elaboration of placental stem villous vessels from pregnancies complicated by intrauterine growth restriction (IUGR) with absent end-diastolic flow velocity detected prior to delivery in the umbilical artery. DESIGN: Comparison between IUGR and control groups of the distribution, in 15 microns increments of 600 randomly chosen stem vessel profiles (post-fixation diameter 10-160 microns) identified by immunohistochemical localisation of alpha-smooth muscle actin in the vessel media. SETTING: Clinical teaching hospital and university anatomy department. SUBJECTS: Paraffin-fixed blocks obtained from placentas of eight pregnancies complicated by IUGR and eight gestational age-matched controls. RESULTS: The distribution of the stem villous vessels in the IUGR placentas, as assessed by the mean vessel diameter in each case, did not differ from the controls (mean vessel diameter 31.8 microns [SD 2.4] vs 29.6 microns [2.3]; P = 0.13). In five IUGR cases alpha-smooth muscle actin positive cells (myofibroblasts) were identified within the stroma of nonmuscularised peripheral (mature intermediate and terminal) villi, but in none of the controls. CONCLUSIONS: Our data do not support the theory that IUGR with absent end-diastolic flow velocity in the umbilical artery is due to a selective loss of small stem villous vessels. The increased impedance in this condition may be conferred more distally within the nonmuscularised capillaries of the peripheral villi.

Actins

[Thrombolytic therapy of acute myocardial infarct in advanced age (based on 2 case reports)].

The introduction of thrombolysis has reduced the mortality of acute myocardial infarction (MI) by 25%. Large-scale studies have revealed that especially patients over 65 benefit from this therapy. Nevertheless, many centers apply an age limit for thrombolytic therapy due to the higher risk of stroke or bleeding in elderly patients. In 1993 181 patients suffering from acute MI were admitted to the intensive care unit of the University Clinic of Internal Medicine, Graz, and 54 (29.4%) of them were treated with fibrinolytic drugs. In this paper we report on the successful thrombolytic management of acute MI in two male patients (87 and 88 years old) who were treated with 100 mg recombinant tissue-type plasminogen activator complex. As a sign of successful reperfusion a rapid increase in plasma creatinine kinase levels and fast amelioration of the ischemia-related ECG changes were observed. In the follow-up examination after four months the first patients showed only minimal exertional dyspnea and was otherwise well. The second patient died one month after MI following a laparotomy for ileus. We draw the conclusion that patients of advanced age also benefit from thrombolytic treatment of acute myocardial infarction, but the indications and contraindications have to be carefully observed.

Aged

The fine structure of normal and ectopic (tubal) human placental villi as revealed by scanning and transmission electron microscopy.

The aim of this study was to examine the development of chorionic villous trees during early periods of normal intrauterinal and ectopic (tubal) pregnancies, and to study the structural specializations on the free surface of mature placental villi by scanning and transmission electron microscope (SEM and TEM). In order to study the structures of placental villi between 28 and 34 days old (pc), early, 6-8 week normal and ectopic, and full term human placenta samples were obtained from legal curettage and hysterectomized cases, and spontaneous deliveries, and tissues samples were prepared for SEM and TEM. Three-dimensional configurations of the developing chorionic villous trees were observed as large main villus groups, covered with abundant microvilli of different size and diameters. It appeared that the chorionic villous trees which emerged from the chorionic plate divided gradually into branches of which ramifications originated as buds. These buds gradually grew and were transformed into shoots. The number of developing new villi appeared to increase gradually from 28 days to 9 weeks (pm) of gestation. From the 4th week onwards the massive trophoblastic sprouts were observed on the surface of main chorionic villi which transformed into primary, secondary and tertiary villous trees. When the placental villi formation in ectopic pregnancy was compared with the intra-uterinal pregnancy, an arrested development was remarkable. The configurations of ectopic placental villi seemed to be disparate, such as curved lines or compressed and wrinkled positions so that the three dimensional aspect had been wizened. The ramification and new villi formation seen as in the normal placenta were not only decreased but also infrequent. Some placental villi samples displayed a gradually thinning terminal region. Trophoblastic degenerations were frequently found on the surface of ectopic villi ultrastructurally. According to these results, we comment that in ectopic pregnancy the placental villi formation and development could have been delayed. At term, some specialized structural modifications were observed on the free surface of the mature placental villi. The presence of some dome-like balloonings and many crateriform hollows were the most striking features of the mature intermediate and terminal villi. According to the increasing physiological needs of the growing fetus, these special structures that are related to lung-like and kidney-like functions and named "nephropneumonic-like units", formed in the mature placental barrier. We have observed that these special units were showing a smooth surface similar to an inflated balloon.(ABSTRACT TRUNCATED AT 400 WORDS)

Chorionic Villi

Quantification and comparison of some natural sphingomyelins by on-line high-performance liquid chromatography/discharge-assisted thermospray mass spectrometry.

Sphingomyelins obtained from bovine brain, chicken egg yolk and bovine milk fat were analysed. Separation was performed by reversed-phase high-performance liquid chromatography utilizing a binary solvent gradient consisting of n-butanol-water-1-propanol-isooctane. Detection was accomplished by light scattering and on-line discharge-assisted thermospray (plasmaspray) ionization mass spectrometry. The positive ion mass spectra exhibit prominent ions related to the amine base structure and fragments which can be utilized for identification of molecular species. The abundance of the fragments containing the fatty acid reflects relatively well the fatty acid composition of natural sphingomyelin mixtures. Bovine brain sphingomyelin has, for example, two distinctive major molecular species composed of C24:1 and C18:0 acids as indicated by the m/z 630.6 and m/z 548.5 ions, respectively. While egg yolk exhibits ions of m/z 520.6 which indicate the presence of C16:0, bovine milk sphingomyelin has several prominent ions of m/z 632.5, 618.6 and 604.7, reflecting the proportions of C24:0, C23:0 and C22:0, respectively.

Animals

Impact of long-term hemodialysis on nutritional status in patients with end-stage renal failure.

We evaluated the way in which duration of hemodialysis treatment affects nutritional status in 96 end-stage renal failure patients. According to the length of previous hemodialysis treatment patients were divided into the groups: onset hemodialysis (ON-HD), early-stage hemodialysis (ES-HD, 1-8 months), mid-stage hemodialysis (MS-HD, 9-69 months), and advanced-stage hemodialysis (AS-HD, 70-207 months). Nutritional status was assessed by laboratory data (serum proteins, total lymphocyte count), intradermal skin antigen testing, anthropometric measurements (body mass index [BMI], infrared interactance), and records of food intake. ON-HD patients on a low-protein diet exhibited abnormally low values for serum total protein, albumin, transferrin, and total lymphocyte count and a high prevalence of anergy to skin antigens (69%). In the ES-HD and MS-HD groups values for serum proteins and total lymphocyte count were in the normal range and significantly higher than in ON-HD patients. In addition, a lower proportion of cutaneous anergy was observed (50% and 27%, respectively). Long-term hemodialysis therapy for 6-17 years (AS-HD) was associated with normal levels for all measured serum proteins. Subnormal levels of total lymphocyte count, significantly lower than in MS-HD patients, were associated with an increase in anergy to skin antigens (46%). Serum prealbumin, complement C3c, BMI, body fat, and lean body mass exhibited normal values in all patients and showed no differences between groups. These results indicate that diminished visceral protein stores, lymphopenia, and anergy to skin antigens are widespread in undialyzed uremic patients with end-stage renal failure but become uncommon after the initiation of regular hemodialysis therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Immunohistochemistry of carbonic anhydrase in human placenta and fetal membranes.

The localization of human carbonic anhydrase (CA) isoenzymes HCA I, HCA II, and rat CA II have been studied in human umbilical cord, chorion laeve including amnion and placenta from first and second trimester and also from term pregnancies. Detection techniques of immunofluorescence and immunoperoxidase were used in cryostat and paraffin sections. Both isoenzymes were found in the villous syncytiotrophoblast throughout pregnancy. HCA I staining patterns in the villous endothelium were highly variable whereas increasing immunoreactivity levels of endothelial HCA II were detected as pregnancy advances. The extravillous cytotrophoblast showed generally weaker levels of immunoreactivity. In amnionic epithelium of membranes, chorionic plate and umbilical cord, higher activities for HCA I, HCA II and rat CA II were found than in all other localizations. Our findings emphasize the importance of enzyme mediated bicarbonate/CO2 removal from the feto-placental unit as opposed to simple bicarbonate diffusion or carrier mediated transport. As effective transfer routes should be considered not only umbilical cord--placental villi--intervillous space, but also fetal kidney--amnionic fluid--amnion--uterine vessels.

Amnion

Insulin receptors in syncytiotrophoblast and fetal endothelium of human placenta. Immunohistochemical evidence for developmental changes in distribution pattern.

The localisation of insulin receptors (IR) was investigated on cryosections of human non-pathologic first trimester and full term placentae by indirect immunohistochemistry with three different monoclonal antibodies (MABS). In placentae from 6 to 10 weeks postmenstruation (p-m.), only syncytiotrophoblast was stained, predominantly that of mesenchymal villi and syncytial sprouts, which are areas of high proliferative activity. In placentae from 11 to 14 weeks p-m., endothelial cells commenced to react with the IR MABS and the syncytiotrophoblast was less intensely labelled than at weeks 6 to 10 p-m. In term placentae, the microvillous membrane of the syncytiotrophoblast showed only patches of weak immunoreactivity. In contrast, the endothelial cells in the placenta but not in the umbilical cord were strongly stained. The amniotic epithelium in the chorionic plate and fibroblasts in the stroma were conspicuously labelled. The data indicate: (1) the receptor density on villous syncytiotrophoblast decreases and that of fetal endothelium increases' throughout gestation; (2) syncytiotrophoblast of human term placentae expresses a low level per unit area of surface IR; and (3) the majority of IR in human term placentae is located in fetal endothelium. Apart from yet unknown functional effects of maternal and fetal insulin at the placental barrier, the results suggest a growth promoting effect on the trophoblast of maternal insulin in first trimester as well as developmental effects of fetal insulin on the feto-placental vessels at term.

Antibodies, Monoclonal

Serum prolactin response to repetitive epileptic seizures.

We measured postictal prolactin (PRL) levels during repetitive seizures in 14 patients (10 men and 4 women) suffering from epilepsy with focal and/or secondarily generalized seizures. Between two and six seizures occurred per patient (mean 2.7). The interveral between seizures was 15 min and 8 h 40 min (mean 3 h 32 min). Five of the 14 patients showed a marked postictal PRL rise after each seizure (i.e. concentrations above 700 microU/ml for women, 500 microU/ml for men). In the remaining 9 patients there was no detectable rise in PRL. A decrease in PRL did not occur in any of the 14 patients. In those patients who had shown a marked PRL increase after the first seizure, the PRL continued to rise in subsequent seizures. Unlike previous investigations, these results show that repetitive epileptic seizures are not necessarily followed by a decrease in postictal PRL levels. A decrease in PRL response is known to occur if there is progression to status epilepticus.

Adolescent

Placental structure: in a comparative aspect.

The outstanding structural diversity of the placenta among mammals, i.e. horse, pig, domestic ruminants, cat. Guinea pig and human, has been studied in a comparative manner using terms of classification such as: type of placental membranes, placental shape, placental maternofetal interdigitation, layers of the placental interhemal barrier, trophoblast invasiveness and decidual cell reaction, formation of syncytiotrophoblast, maternofetal blood flow interrelationships, and placental separation at birth. These terms, originating partly from classical acquirements of knowledge and partly from recent research, are presented and new aspects discussed; thus helping towards a better understanding of the structure and function of the different placental types.

Animals

Immunohistochemistry of two different types of placental fibrinoid.

The structure and composition of human placental fibrinoid were studied on cryostat and paraffin sections and by transmission electron microscopy as well as immunohistochemistry using antibodies directed against fibrin, fibronectin isoforms, collagens IV and VI, laminin and tenascin. The findings suggest two structurally and immunohistochemically different subtypes of fibrinoid: fibrin-type fibrinoid and matrix-type fibrinoid. Fibrin-type fibrinoid was characterized by immunoreactivity for fibrin and cellular fibronectin, including the ED-A sequence. Immunostaining for all other extracellular matrix molecules was negative. Ultrastructurally, this fibrinoid subtype consisted of a meshwork of fibers with 20-nm cross striation typical of fibrin. Fibrin-type fibrinoid never contained extravillous trophoblast cells. It is therefore primarily a blood clot product derived from maternal and fetal blood. In contrast, matrix-type fibrinoid showed virtually no evidence of fibrin; it was immunopositive for extracellular matrix molecules such as the fibronectins, particularly oncofetal fibronectin (containing the ED-B sequence), collagen IV, laminin and tenascin. Oncofetal fibronectin, which was neither expressed in fibrin-type fibrinoid nor in the villous stromal core, seemed to be a specific marker for matrix-type fibrinoid. Single or clustered nonproliferative extravillous trophoblast cells were embedded within the matrix molecules. It is very likely that these cells secrete the matrix in a non-polarized fashion. Fibrin-type fibrinoid would appear to be involved in shaping the intervillous space and in replacing damaged syncytiotrophoblast acting as a transport and immune barrier. Matrix-type fibrinoid, as a secretory product of the extravillous trophoblast, should be discussed in context with the invasive properties of this cell population.

Cell Adhesion Molecules, Neuronal