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Biomedical subjects

M Roth

Publications and source records attributed to M Roth.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Nutritional deficiencies and complications in chronic inflammatory bowel diseases].

BACKGROUND: Deficiencies of vitamins and trace elements are frequent in inflammatory bowel disease. Aim of this study was to evaluate retrospectively the prevalence of these deficiencies and of liver complications in a large population. PATIENTS AND METHODS: The records from 392 out-patients, 279 with Crohn's disease (160 female, 119 male) and 113 with ulcerative colitis (56 female, 57 male) were analyzed. RESULTS: Deficiencies were found in 85% of patients with Crohn's disease vs 68% with ulcerative colitis during the course of the disease, predominantly a deficiency of iron and of calcium. Less frequently deficiencies of zinc, protein, cyanocobalamin, and folic acid were found. Elevated liver enzymes were seen in 38% of patients with Crohn's disease vs 27% with ulcerative colitis. In order of frequency: gamma-glutamyl-transferase, ALAT, AP, ASAT, and bilirubin. Gallstones were present in 12% of patients with Crohn's disease and 4% with ulcerative colitis. 6% of patients with Crohn's disease and 4% with ulcerative colitis had kidney stones. CONCLUSIONS: In view of the high frequency of deficiencies in patients with inflammatory bowel disease it seems to be important to check frequently for extraintestinal complications.

Adolescent↗
PubMed1998

Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells.

The vascular endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial cells and enhances vascular permeability and edemagenesis. VEGF is also a major regulator of angiogenesis and may be a key target for inhibiting angiogenesis in angiogenesis-associated diseases. Among the extensively studied angiostatic compounds are several corticosteroids when used alone or in combination with heparin. In this study we present evidence for an additional mechanism of action of hydrocortisone, cortisone and dexamethasone in inhibiting edemagenesis or angiogenesis. In cultures of aortic human vascular smooth muscle cells these corticosteroids (1 x 10(-8) to 1 x 10(-12) M) abolished the platelet-derived growth factor-induced (PDGF) expression of the VEGF gene in a dose-dependent manner. In contrast, two precursors of corticosteroids, desoxycorticosterone or pregnenolone, did not affect PDGF-induced VEGF expression. Our findings indicate that the capacity of corticosteroids to reduce edema or to prevent new blood vessel formation may be attributed, at least in part to the ability of these agents to abolish the expression of VEGF.

Anti-Inflammatory Agents↗
PubMed1998

Late paraphrenia: a variant of schizophrenia manifest in late life or an organic clinical syndrome? A review of recent evidence.

A large amount of research has been devoted during the past 15 years to the clinical and neurobiological aspects of the disorder named as 'late paraphrenia' (LP) in 1955. The symptomatology and diagnosis of the disorder, its prognosis, the cognitive functioning of those affected, the structural changes in the brain as revealed by modern techniques of brain imaging and its postmortem neuropathology have all been submitted to investigation. The results have been widely regarded as consistent with the concept of LP as an organic disease of the brain, but increased knowledge of the neurobiology of schizophrenia and of the age-related changes that occur in the brains of elderly people casts doubt on the validity of this interpretation. The findings are consistent with the view that LP is the form in which schizophrenia is manifest in old age. The proposal that LP has a closer kinship with affective disorder than with schizophrenia is part of a general theory of the sex differences in schizophrenia. In LP it becomes entangled with the organicity hypothesis, suggesting that neither of these explanations is adequate, and most of the evidence points to a unitary concept which views LP as a variant of a single disorder, namely schizophrenia, which, however, requires a broad definition. This concept has implications for fresh paths of enquiry.

Aged↗
PubMed1998

The differential distribution of hyaluronic acid in the layers of human atheromatic aortas is associated with vascular smooth muscle cell proliferation and migration.

Vascular smooth muscle cells (VSMC), under conditions of induced proliferation, similar to those involved in atherosclerosis, secrete an acidic glycan, 82% of which exhibits structural homology with hyaluronic acid (HA), has a molecular mass of 340 kDa (HA-340) and inhibits VSMC proliferation in vitro. In this study, the expression of glycans was investigated in human atheromatic aortas and evidence is presented that a HA molecule, similar to HA-340, is distinctly expressed in all aortic layers. The isolation of the glycans from human aortas was performed after homogenization of the individual aortic layers (atheromatic plaque, tunica intima, tunica media and tunica adventitia), by lipid extraction and extensive digestion with pronase and DNase. The total glycans were purified from the digestion products by gel filtration on Sephadex G-25 and fractionated on a Superose 6 column. Enzymatic treatment of the ensuing glycan fractions with all known glycosaminoglycan-degrading enzymes, followed by electrophoresis on polyacrylamide gradient gels and cellulose acetate membranes, revealed that, in addition to HA, the tunica intima and the atheromatic plaque also contained dermatan sulfate, while the tunica media and the tunica adventitia also contained chondroitin sulfates and heparan sulfate. The highest concentration of the human aorta HA was found in the tunica media, exhibiting a negative concentration gradient from the tunica media to the atheromatic plaque. Investigation of the biological function of the human aorta HA revealed that this molecule acts as a negative regulator on the PDGF-induced VSMC proliferation and as a positive regulator on the PDGF-induced VSMC migration. The differential expression of HA within the aortic layers correlates with the biological function attributed to this acidic glycan and associates it with key events in the progression of atherogenesis.

Adult↗
PubMed1998

The cellular immune responses induced in the follow-up of interferon-alpha treated patients with chronic hepatitis C may determine the therapy outcome.

BACKGROUND/AIMS: To study whether the host's immune response determines viral clearance in chronic hepatitis C, virological markers and antigen-specific T cell reactions were analysed in 30 chronic HCV carriers followed up during interferon-alpha therapy, 11 untreated anti-HCV positive individuals and 10 healthy controls. METHODS: Proliferative T helper cell responses to recombinant HCV core and non-structural antigens were monitored by 3H-thymidine uptake assay and compared to quantitative viraemia levels and HCV genotypes. RESULTS: Of the 30 treated patients, six had sustained complete responses (20%), another six were transient therapy responders (20%) and 18 were non-responders (60%). Viral clearance was associated with the HCV genotype 3 and low pretreatment viral load. In a substantial proportion of complete and transient therapy responders, increased NS3-, helicase- and NS4-antigen-specific T cell responses were observed during interferon-alpha therapy. In non-responders and in the later clinical courses of transient therapy responders, core and NS5-specific T cell responses dominated. In addition, 11 untreated anti-HCV antibody positive individuals were studied. Two HCV-RNA negative patients who might have recovered from HCV infection showed strong persistent lymphoproliferative responses to NS3, helicase and NS4 antigens, whereas seven of the nine viraemic patients reacted with HCV core or NS5 antigens. CONCLUSIONS: Interferon-alpha treatment enhances NS3-, helicase- and NS4-antigen-specific T helper cell responses in patients with viral clearance, whereas viral persistence was associated with increased T cell reactivities against core and NS5 antigens. Immunogenetical, immunological and virological factors that may influence differential T cell induction in chronic hepatitis C are discussed.

Adult↗
PubMed1998

Compartmentalization of pro-inflammatory cytokines in tuberculous pleurisy.

Increased levels of interleukin-6 (IL-6) and IL-8 are found in various immunologically mediated inflammatory disorders. Concentrations of IL-6, IL-8 and the soluble form of the IL-6 receptor (sIL-6R) were determined in serum and effusion fluid of 25 patients with tuberculous pleurisy utilizing enzyme linked immunosorbent assays (EIA). Serum IL-6 levels were only slightly increased in patients with tuberculous pleurisy in comparison to controls (11.1 +/- 2.1 vs 7.3 +/- 1.0 pg ml-1). IL-8 could not be detected in the serum of tuberculosis patients, but it was detected in the serum of healthy controls (8.0 +/- 1.5 pg ml-1). In comparison to serum, IL-6 and IL-8 were found in high concentrations in pleural effusions (IL-6: 932 +/- 70 vs 11.1 +/- 2.1 pg ml-1, P < 0.0001; IL-8: 450 +/- 85 vs 0 +/- 0 pg ml-1). In contrast, sIL-6R concentrations were much higher in serum compared to pleural effusion levels [30,477 +/- 1905 vs 9881 +/- 1177 pg ml-1, P < 0.0001 (mean +/- SEM)]. The authors conclude that elevated levels of IL-6 and IL-8 in pleural effusions are compartmentalized at the site of active disease. The low levels of sIL-6R in the presence of high levels of IL-6 in pleural effusions, and the high levels of sIL-6R in the presence of low levels of IL-6 in serum suggest that the expression or shedding of sIL-6R may be downregulated in the presence of excessive amounts of IL-6.

Adult↗
PubMed1998

Parenteral nutrition facilitates activation of coagulation but not of fibrinolysis during human endotoxemia.

Venous thrombosis and bacterial infections are common complications of parenteral nutrition. To test the hypothesis that infection facilitates activation of coagulation during parenteral nutrition, healthy subjects were intravenously injected with endotoxin (2 ng/kg) after they had received either 1 week of standard parenteral nutrition (n = 7) or normal enteral feeding (n = 8). Compared with enteral feeding, parenteral nutrition was associated with a selectively enhanced activation of the coagulation system (plasma levels of thrombin-antithrombin III complexes) during endotoxemia. Activation of the fibrinolytic system (plasminogen activator activity, tissue-type plasminogen activator, plasminogen activator inhibitor type 1) proceeded similarly in both study groups. In patients receiving parenteral nutrition, one common complication (bacterial infection) may facilitate the occurrence of another common complication (venous thrombosis) by synergistic stimulation of the coagulation system.

Adult↗
PubMed1998

A 340 kDa hyaluronic acid secreted by human vascular smooth muscle cells regulates their proliferation and migration.

The formation of atherosclerotic lesions is characterized by invasion of vascular smooth muscle cells (VSMC) into the tunica intima of the arterial wall and subsequently by increased proliferation of VSMC, a process apparently restricted to the intimal layer of blood vessels. Both events are preceded by the pathological overexpression of several growth factors, such as platelet-derived growth factor (PDGF) which is a potent mitogen for VSMC and can induce their chemotaxis. PDGF is generally not expressed in the normal artery but it is upregulated in atherosclerotic lesions. We have previously shown that PDGF-BB specifically stimulates proliferating VSMC to secrete a 340 kDa hyaluronic acid (HA-340). Here, we present evidence regarding the biological functions of this glycan. We observed that HA-340 inhibited the PDGF-induced proliferation of human VSMC in a dose-dependent manner and enhanced the PDGF-dependent invasion of VSMC through a basement membrane barrier. These effects were abolished following treatment of HA-340 with hyaluronidase. The effect of HA-340 on the PDGF-dependent invasion of VSMC coincided with increased secretion of the 72-kDa type IV collagenase by VSMC and was completely blocked by GM6001, a hydroxamic acid inhibitor of matrix metalloproteinases. HA-340 did not exert any chemotactic potency, nor did it affect chemotaxis of VSMC along a PDGF gradient. In human atheromatic aortas, we found that HA-340 is expressed with a negative concentration gradient from the tunica media to the tunica intima and the atheromatic plaque. Our findings suggest that HA-340 may be linked to the pathogenesis of atherosclerosis, by modulating VSMC proliferation and invasion.

Aorta↗
PubMed1998

HBW 023 (recombinant hirudin) for the acceleration of thrombolysis and prevention of coronary reocclusion in acute myocardial infarction: results of a dose-finding study (HIT-II) by the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte.

OBJECTIVE: To define an optimal dose of hirudin that would improve early coronary artery Thrombolysis in Myocardial Infarction grade 3 (TIMI 3) patency and prevent reocclusions in patients with acute myocardial infarction treated with front-loaded recombinant tissue-type plasminogen activator (rt-PA). METHODS: Recombinant hirudin (HBW 023) was tested in a sequential dose-escalating study as adjunct to front-loaded rt-PA in 143 patients with acute myocardial infarction. The sequential model was assigned two 'decision boundaries': it triggered an increase in dosage if the 60-min TIMI 3 flow rate in a dosage group was statistically not consistent with a target patency rate of 75%, or if the deterioration in coronary blood flow (of at least one TIMI grade, from TIMI 2 or 3, from one angiography to the next) exceeded 5%. RESULTS: The decision boundary for TIMI 3 flow grade at 60 min was crossed when 18 patients were treated with 0.1/0.06 mg/kg (bolus/infusion per hour over 48 h) r-hirudin (dosage group I), 42 patients treated with 0.2/0.1 mg/kg (dosage group II), and 83 patients with 0.4/0.15 mg/kg (dosage group III). TIMI 3 flow at 60 min was 50%, 58%, and 63% in dosage groups I-III, respectively (P = 0.15). Early, complete, and sustained patency (TIMI 3 flow at 60 min, 90 min and 48 h) were 44%, 55% and 64% (P = 0.07). Reocclusion between 90-min and 48-h angiograms or reinfarction occurred in 0 to 15, two of 36, and one of 72 patients, respectively (P = 0.5). Four patients (2.8%) died in hospital and 14 patients suffered a major bleeding event, but no intracranial bleeding was encountered. CONCLUSIONS: With increasing doses of hirudin, there was a trend towards greater early and complete patency, but no clear dose--response relationship was observed. A borderline significant effect was observed with respect to early, complete, and sustained patencies. In all groups, reocclusions or reinfarctions were rare. Neither clinical nor laboratory data predicted the imbalance in haemorrhagic events observed in a subsequent, prematurely terminated, phase III trial with hirudin and rt-PA.

Adult↗
PubMed1998

Serum concentration of calcium, 1,25 vitamin D and parathyroid hormone are not correlated with coronary calcifications. An electron beam computed tomography study.

BACKGROUND: The amount of coronary artery calcification, measured using electron beam computed tomography, is correlated with the volume of coronary artery atherosclerotic plaque, the severity of stenosis by angiography, and with the likelihood of future cardiovascular events. The deposition of calcium in atherosclerotic plaques may also be influenced by determinants of calcium metabolism, thus contributing to the variance of the relation between coronary artery calcification and extent of atherosclerosis. Our objective was to determine whether this variance could be explained by differences in the parameters of calcium metabolism. DESIGN AND METHODS: We measured serum concentrations of calcium, 1,25(OH)2 vitamin D and parathyroid hormone (PTH) in 50 subjects undergoing angiography for clinical indications, and evaluated the correlations between these concentrations and calcium deposition in the coronary arteries, and the ratio of calcium deposition to extent of atherosclerosis using coronary angiography. RESULTS AND CONCLUSIONS: Serum concentrations of calcium 1,25(OH)2 vitamin D and PTH were not correlated with coronary calcification or the ratio of coronary calcification to the extent of coronary stenosis. We conclude that, in subjects undergoing coronary angiography, the variance of the relationship between coronary atherosclerosis and coronary calcium is not a result of differences in serum concentrations of calcium, 1,25(OH)2 vitamin D or PTH.

Aged↗
PubMed1998

Proinflammatory cytokine levels in patients with lung cancer and carcinomatous pleurisy.

Increased levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have been reported in various diseases, including lung cancer. The role of the soluble form of the IL-6 receptor (sIL-6R) remains to be explored. We therefore measured IL-6, IL-8 and sIL-6R in effusion fluid and blood serum of 10 lung cancer patients with carcinomatous pleurisy (5 men, 5 women, age 64.3 +/- 4.4 years) by enzyme-linked immunosorbent assays. Serum levels of healthy individuals served as control. Concentrations of sIL-6R were much higher in serum compared to pleural effusion fluids of tumor patients (25,698 +/- 1,993 vs. 9,438 +/- 1,407 pg/ml: p < 0.0001). In contrast, IL-6 and IL-8 were found at high concentrations in carcinomatous pleural effusions in comparison to serum (IL-6: 964 +/- 176 vs. 10.2 +/- 1.3 pg/ml, p < 0.0001; IL-8: 319 +/- 85 vs. 9.6 +/- 9.6 pg/ml, p < 0.0001). The serum concentrations of IL-6 were not significantly increased in lung cancer patients (10.2 +/- 1.3 pg/ml) in comparison to controls (7.3 +/- 1.0 pg/ml). IL-8 was detected in the serum of only 1 patient and in low levels in the serum of controls (8.0 +/- 1.5 pg/ml; all values are mean +/- SEM). We conclude from this study that decreased levels of sIL-6R, but increased levels of IL-6 and IL-8, are found in pleural effusion fluid of patients with lung cancer and carcinomatous pleurisy. The low sIL-6R levels in the presence of high IL-6 levels in pleural effusions and the high sIL-6R levels in the presence of low IL-6 levels in serum may suggest a downregulation of sIL-6R expression of sIL-6R shedding in the presence of excessive amounts of IL-6.

Aged↗
PubMed1998

Hypoxia-induced interleukin-6 and interleukin-8 production is mediated by platelet-activating factor and platelet-derived growth factor in primary human lung cells.

Hypoxia has been shown to induce the expression of different growth factors, cytokines, and proinflammatory mediators, including platelet-derived growth factor (PDGF), interleukin-6 (IL-6), interleukin-8 (IL-8), and platelet-activating factor (PAF) in animal models. PAF and PDGF are thought to play important roles in vascular remodeling and have been shown to induce expression of IL-6 and IL-8 genes under normoxic conditions. We hypothesize that de novo synthesis of IL-6, IL-8, and cell proliferation is enhanced in human pulmonary cells under hypoxic cell culture conditions. We further assumed an important role of PAF and/or PDGF in hypoxia-induced cell activation. Using cultures of primary human pulmonary fibroblasts and pulmonary vascular smooth muscle cells (VSMC) we show that hypoxia (3% O2) induced transcription and translation of IL-6 (4- to 5-fold) and IL-8 (5- to 6-fold) in both cell types. Hypoxia-induced expression of IL-6 was suppressed by 50% to 60% in the presence of the PAF antagonist WEB2170, or neutralizing anti-PDGF antibodies. In addition, we demonstrate that hypoxia induces a threefold increase of cell proliferation of fibroblasts and a twofold increase of VSMC proliferation. Similar to the effect on IL-6 and IL-8 synthesis, WEB2170 or neutralizing anti-PDGF antibodies downregulated hypoxia-induced proliferation of fibroblasts and VSMC by 50%. Our data show that PAF and PDGF are important mediators for hypoxia-induced cell activation and cytokine release in the human lung. We therefore hypothesize that IL-6 and IL-8 contribute to the progression of lung diseases associated with hypoxia, and that both proinflammatory factors, PAF and PDGF, are involved in hypoxia-dependent expression of IL-6 and IL-8 in human pulmonary fibroblasts and VSMC.

Cell Division↗
PubMed1998

Proliferation of human non-small-cell lung cancer cell lines: role of interleukin-6.

Interleukin-6 (IL-6) is involved in regulation of the immune response, acute phase reaction, and cell proliferation. The aim of this study was to investigate whether IL-6 is implicated in cell proliferation of human non-small-cell lung cancer (NSCLC) cell lines. We analyzed IL-6 messenger RNA (mRNA) and protein expression in eight NSCLC cell lines: A549, Calu3, Calu6, H23, H522, H810, H1155, and H1299. The A549, Calu3, Calu6, and H23 cell lines expressed IL-6 mRNA and protein. In these cell lines, fetal calf serum (FCS) significantly increased cell proliferation as assessed by thymidine incorporation. In the presence of IL-6 antisense oligonucleotides, both proliferation and IL-6 synthesis were downregulated. In contrast, IL-6 mRNA and protein could not be detected in the NSCLC cell lines H522, H810, H1155, and H1299. In these NSCLC cell lines, FCS only marginally increased cell proliferation and IL-6 antisense oligonucleotides did not affect cell proliferation. The addition of neither exogenous IL-6 nor neutralizing anti-IL-6 antibodies affected cell proliferation in any of the experiments. Our data thus provide evidence that intracellular IL-6 is required in the control of cell proliferation in a subset of human NSCLC cell lines. We suggest the existence of two subtypes of NSCLC, an IL-6-dependent and an IL-6-independent type.

Antibodies↗
PubMed1998

Revision endoscopic sinus surgery: the Thomas Jefferson University experience.

Since its introduction, functional endoscopic sinus surgery (FESS) has demonstrated success rates of 76% to 98%. A small group of the patients in whom initial FESS and optimal medical therapy fail require revision endoscopic sinus surgery (RESS). This group has recently been studied by several authors, and we have evaluated a group of 90 RESS patients selected from 753 consecutive primary FESS patients. Patients were followed for a mean of 22.8 months. Extent of disease, history of polyps, allergy, previous traditional endonasal sinus surgery, male gender, chronic steroid use, and the presence of a deviated septum all appeared to adversely affect RESS outcome. The surgeon's knowledge of the sinus anatomy is critical, especially in revision sinus cases in which landmarks are distorted or absent. In our review, RESS was associated with a 1% major complication rate and was successful in 67% of patients. Computer-assisted endoscopic sinus surgery integrates preoperative imaging with realtime endoscopic visualization, augments the surgeon's knowledge of anatomy, and helps to minimize patient risk.

Adult↗
PubMed1998

[Depersonalization experiences in adolescents].

OBJECTIVES: The present study examined how widespread experiences of depersonalization are in adolescence and how they are connected to self-esteem and self-awareness. METHODS: We tested 352 adolescents aged 12 to 16 years by means of standardized questionnaires. RESULTS: The results show: (1) that the majority of adolescents has had few experiences of depersonalization. (2) We observed clear sex differences in the course of age. Among female adolescents the number of experiences of depersonalization increased with age, whereas among male adolescents the number began to decrease in mid-adolescence. (3) Adolescents whose experiences of depersonalization are intense do not differ from their counterparts in the study with regard to self-esteem; however, their sense of self-awareness is heightened. The results are discussed in respect to the formation of identity in adolescence.

Adolescent↗