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Biomedical subjects

M Vogt

Publications and source records attributed to M Vogt.

At least 73 records · Page 4Linked to original sources
PubMed1998

Efficacy, safety, and tolerance of piperacillin/tazobactam compared to co-amoxiclav plus an aminoglycoside in the treatment of severe pneumonia.

An open, randomized, multicenter study was conducted to compare the efficacy and safety of piperacillin/tazobactam and co-amoxiclav plus aminoglycoside in the treatment of hospitalized patients with severe community-acquired or nosocomial pneumonia. Of the 89 patients who entered the study, 84 (94%) were clinically evaluable. A favorable clinical response was observed in 90% of the piperacillin/ tazobactam group and in 84% of the co-amoxiclav/aminoglycoside group (not significant). The bacteriological efficacy was comparable in both groups (96% vs. 92%; not significant). There was only one fatal outcome in the piperacillin/tazobactam group compared to six in the co-amoxiclav/aminoglycoside group regimen (P=0.058). The adverse event rate was non-significantly lower in the piperacillin/ tazobactam group compared to the co-amoxiclav/aminoglycoside group (2% vs. 7%; P=0.32). Piperacillin/tazobactam is safe and highly efficacious in the treatment of serious pneumonia in hospitalized patients. It compares favorably with the combination of co-amoxiclav/aminoglycoside.

Aged↗
PubMed1998

[100 MHz ultrasound of psoriasis vulgaris plaque].

PURPOSE: 20 MHz sonography of inflammatory diseases has concentrated on the evaluation of the echo-poor area in the upper dermis. With regard to higher resolution, this study focuses on the alterations of the epidermis and upper dermis skin using 100 MHz sonography. METHOD: 70 fully developed psoriasis vulgaris plaques of 20 patients were examined using our 100 MHz ultrasound equipment after application of salicylic acid in petrolatum for 24 h. After informing the patient about the aims of the study, a small knife biopsy was taken from 11 plaques. RESULTS: All psoriasis plaques exhibited, in comparison with normal skin, a significant widening of the skin entry echo (p < 0.001). Focally, this echo-rich line broke up into two thinner lines. Correlating histology exhibited in these areas an orthohyperkeratosis and focal parakeratosis. The upper dermis showed an echo-poor, band-shaped area which corresponded histologically to an acanthosis, elongation of rete ridges, and widening of the stratum papillare. The mean grey level of the echo-poor area and of the dermis beneath was significantly lower (p < 0.001) than the normal adjacent dermis. The thickness of the echo-poor area correlated with the thickness of the sum of the acanthosis and the inflammatory infiltrate in the histological sections (r = 0.94). CONCLUSION: Using 100 MHz sonography changes of the skin entry echo and the upper dermis can be visualized and quantified.

Adult↗
PubMed1998

Expression of fos and jun genes in human skeletal muscle after exercise.

It is believed that the induction of the fos and jun gene family of transcription factors might be at the origin of genetic events leading to the differential regulation of muscle-specific genes. We have investigated the effect of a 30-min running bout in untrained subjects on the expression of the mRNAs of all members of the fos and jun gene families, including c-fos, fosB, fosBdel, fra-1, and fra-2 as well as c-jun, junB, and junD. While the fos family members were transiently upregulated 10- to 20-fold (an exception being fra-2) the induction of the jun family members was up to 3-fold only. The induction of c-fos could also be demonstrated at the protein level. Both c-fos and c-jun mRNAs were coinduced in muscle fiber nuclei. The induction was not restricted to a particular fiber type, as expected from established muscle fiber recruitment schemes, but followed a "patchy" pattern confined to certain regions of the muscle. The signals leading to the expression of these immediate early genes are therefore unclear.

Adult↗
PubMed1998

Independent induction of senescence by p16INK4a and p21CIP1 in spontaneously immortalized human fibroblasts.

In this work, we address the question of whether replicative senescence can be induced in immortal nontumorigenic human fibroblasts. The immortal fibroblasts used in this study were derived from two Li-Fraumeni (LF) patients who carry in their germ line one wild-type and one mutant p53 allele. Both immortal lines have lost the wtp53 allele and express no detectable p16INK4a protein, although they carry the p16INK4a gene. In contrast to immortal human fibroblasts, senescent human fibroblasts have a low content of 5-methyl-cytosine in their DNA. This observation suggested the possibility that a demethylating agent could revert the immortal phenotype and induce replicative senescence in the immortal cell lines. Cells of the two LF lines were exposed to the demethylating agent 5-aza-2'-deoxycytidine. Within 6 days, all cells were growth arrested and showed the enlarged and flat morphology characteristic of senescent cells, an accumulation of lipofuscin granules and senescence-associated beta-galactosidase activity at pH6, both biomarkers for senescence. Immunoblots of 5-aza-2'-deoxycytidine-treated cells showed a greatly increased expression of p16INK4a protein but no detectable change in the expression of p21CIP1, a gene known to be strongly expressed in senescent normal human fibroblasts. In two other experimental series, cells of the two LF lines were infected with retroviral constructs encoding either p16INK4a or p21CIP1. Each of the transduced genes induced senescence without affecting the expression of the other endogenous gene. The results show that induction of senescence in immortal LF fibroblasts can occur by different pathways: (a) by demethylation-dependent pathways that induce the expression of p16INK4a; and (b) by demethylation-independent pathways involving the expression of p21CIP1. The induction of senescence by p16INK4a and p21CIP1 occurred equally in the two human immortal fibroblast lines, which differed in the length of their telomeres and the activity of their telomerase.

5-Methylcytosine↗
PubMed1997

Characterization and cell cycle regulation of the related human telomeric proteins Pin2 and TRF1 suggest a role in mitosis.

Telomeres are essential for preserving chromosome integrity during the cell cycle and have been specifically implicated in mitotic progression, but little is known about the signaling molecule(s) involved. The human telomeric repeat binding factor protein (TRF1) is shown to be important in regulating telomere length. However, nothing is known about its function and regulation during the cell cycle. The sequence of PIN2, one of three human genes (PIN1-3) we previously cloned whose products interact with the Aspergillus NIMA cell cycle regulatory protein kinase, reveals that it encodes a protein that is identical in sequence to TRF1 apart from an internal deletion of 20 amino acids; Pin2 and TRF1 may be derived from the same gene, PIN2/TRF1. However, in the cell Pin2 was found to be the major expressed product and to form homo- and heterodimers with TRF1; both dimers were localized at telomeres. Pin2 directly bound the human telomeric repeat DNA in vitro, and was localized to all telomeres uniformly in telomerase-positive cells. In contrast, in several cell lines that contain barely detectable telomerase activity, Pin2 was highly concentrated at only a few telomeres. Interestingly, the protein level of Pin2 was highly regulated during the cell cycle, being strikingly increased in G2+M and decreased in G1 cells. Moreover, overexpression of Pin2 resulted in an accumulation of HeLa cells in G2+M. These results indicate that Pin2 is the major human telomeric protein and is highly regulated during the cell cycle, with a possible role in mitosis. The results also suggest that Pin2/TRF1 may connect mitotic control to the telomere regulatory machinery whose deregulation has been implicated in cancer and aging.

Amino Acid Sequence↗
PubMed1997

Activation of transcription factor NF-kappaB and p38 mitogen-activated protein kinase is mediated by distinct and separate stress effector pathways.

Mitogen-activated protein (MAP) kinases are important mediators of the cellular stress response. Here, we investigated the relationship between activation of the MAP kinase p38 and transcription factor NF-kappaB. Different forms of cellular stress were found to preferentially trigger either p38 or NF-kappaB. Arsenite or osmotic stress potently activated p38 but were ineffective in inducing NF-kappaB activation. Tumor necrosis factor-alpha and hydrogen peroxide, in contrast, led to NF-kappaB activation but only modestly stimulated p38. The activation of NF-kappaB was strongly abolished by antioxidants, while the activity of p38 and transcription factor AP-1 were increased. Inhibition of small GTPases including Rac and Cdc42 prevented p38 and AP-1 activation without interfering with NF-kappaB. In addition, inhibition of p38 by a pharmacological inhibitor or a dominant-negative mutant of MAP kinase kinase-6, an activator of the p38 pathway, interfered with NF-kappaB-dependent gene expression but not its DNA binding activity. Our results indicate that activation of p38 and NF-kappaB are mediated by separate pathways, which may converge further downstream in the cell nucleus. Different forms of cellular stress, however, initially trigger distinct signaling cascades involving either oxidative stress or GTPase-coupled pathways.

Activating Transcription Factor 2↗
PubMed1997

Cardiac surgery in a high-risk group of patients: is prolonged postoperative antibiotic prophylaxis effective?

OBJECTIVE: In a prospective, randomized study, postoperatively prolonged antibiotic prophylaxis is evaluated in a high-risk group of patients undergoing cardiac operations. These patients had postoperative low cardiac output necessitating inotropic support and intraaortic balloon pumping. METHODS: Between January 1991 and 1994, 53 patients were enrolled in the study (42 men, mean age 65 years). All patients received the usual perioperative (24 hours) cefazolin prophylaxis. In the study group (n = 28) a prolonged regimen of prophylaxis with ticarcillin/clavulanate was performed for 2 days and vancomycin was added in a low dose until removal of the intraaortic balloon pump. The control group (n = 25) did not receive a prolonged regimen of prophylaxis. Follow-up ended at hospital discharge. RESULTS: Early mortality was 7 of 28 patients (25%) in the prophylaxis group and 8 of 25 patients (32%) in the control group (p = 0.397). Defined infections (pneumonia, n = 22; sepsis, n = 8; deep sternal wound infection, n = 2) occurred in 50% of the study group and 68% of the control group (p = 0.265). In all patients with septicemia, only coagulase-negative staphylococci could be isolated from the bloodstream (5 patients in the prophylaxis group vs 3 in the control group). Infectious parameters were controlled daily and did not differ significantly between groups. A total of 1158 bacteriologic tests were performed (blood cultures, n = 389; intravascular catheters, n = 208; bronchial aspirates, n = 411; intraaortic balloon pumps, n = 42; wound secretions, n = 108) showing bacterial growth in 322 (28%) without a significant difference between the groups. In the prophylaxis group, 13 intravascular catheters and intraaortic balloon pumps showed bacterial growth versus 11 in the control group. No side effects were seen. CONCLUSIONS: In a high-risk group of patients undergoing cardiac operations, infectious outcome could not be effectively influenced by an additional and prolonged postoperative prophylaxis regimen with low-dose vancomycin and ticarcillin/clavulanate. Low-dose vancomycin did not reduce the rate of infections or colonizations of intravascular catheters with gram-positive organisms.

Aged↗
PubMed1997

Evidence for reduced coronary flow reserve in patients with insulin-dependent diabetes. A possible cause for diabetic heart disease in man.

UNLABELLED: In diabetic heart disease myocardial, interstitial, coronary and neural structures are often involved. Coronary microangiopathy is supposed to contribute an essential part, which has not yet been clearly analysed. METHODS: In 9 normotensive patients with insulin-treated diabetes (DP) with clinically suspected coronary heart disease but normal epicardial coronary arteries, coronary microcirculation was studied. Coronary flow was determined as the quotient of base line and minimal coronary resistance after dipyridamole (0.5 mg/kg i.v.), using the argon-gas-chromatography method. Systolic left ventricular function was analysed by ventriculography, diastolic function by M-Mode-echocardiography and Doppler-echocardiograhy. Twelve normotensive subjects served as control group (CON). RESULTS: In diabetic patients maximal coronary flow was significantly reduced (172 +/- 5 versus 395 +/- 103 ml/min x 100 g, p < or = 0.001) and minimal coronary resistance increased (0.6 +/- 0.19 versus 0.24 +/- 0.06 mmHg x min x 100 g/ml, p < 0.001). Coronary reserve in diabetics was markedly reduced (1.84 +/- 0.39 versus 4.23 +/- 0.52, p < or = 0.001). Global systolic function was normal in all patients (EF: DP: 72 +/- 13 versus CON: 77 +/- 12%, n.s.; cardiac index: DP: 3.2 +/- 0.8 versus CON: 3.3 +/- 1.2 1/ min x m2, n.s.). Diastolic function was impaired in diabetics with an increased relaxation time index (97 +/- 23 versus 45 +/- 18 msec, p < or = 0.01) and an impaired diastolic inflow pattern, indicated by the E/A-ratio (0.75 +/- 0.14 versus 1.66 +/- 0.13, p < or = 0.05). CONCLUSIONS: The reduced coronary flow reserve in patients with insulin-treated diabetes mellitus may play a crucial role in the pathophysiology of diabetic cardiopathy, causing myocardial ischaemia due to a disturbance of coronary microcirculation leading to diastolic dysfunction and progressing assumably to systolic failure.

Cholesterol↗
PubMed1997

Severin classification system for evaluation of the results of operative treatment of congenital dislocation of the hip. A study of intraobserver and interobserver reliability.

The Severin classification system frequently is used to evaluate the radiographic results of operations performed for the treatment of congenital dislocation of the hip. However, the reliability of this classification scheme has not been established, to our knowledge. Ideally, a classification system should be validated before it is used to promote therapeutic guidelines or to compare results of treatment; the purpose of the present study was to establish the intraobserver and interobserver reliability of the Severin classification system. Four blinded raters and the operating surgeon independently used the Severin system to evaluate the most recent radiographs of thirty-seven children (fifty-six hips) who had been managed, an average of nine years previously, with a medial open reduction for congenital dislocation of the hip. Three of the raters evaluated the same radiographs again under similar testing circumstances eight weeks later. Ten paired interobserver and three intraobserver comparisons then were analyzed with use of the Cohen kappa coefficient (kappa). The average kappa coefficient for the six pairwise comparisons between the four blinded raters was 0.15 (range, -0.05 to 0.42) when all Severin classes were analyzed independently. The average kappa coefficient for the four pairwise comparisons between the blinded raters and the operating surgeon was even lower (0.02). The kappa coefficients for the three intraobserver comparisons were 0.20, 0.38, and 0.44 (average, 0.34). Kappa analysis demonstrated variable and low levels of agreement when the Severin system was used to rate the results of operations performed for the treatment of congenital dislocation of the hip. We believe that the unadjusted kappa coefficient should indicate excellent agreement (kappa > 0.75) for all comparisons if this system is to be used for the evaluation of clinical results. The unacceptably low levels of intraobserver and interobserver reliability call into question the clinical conclusions of reports in which the Severin system has been used as the basis of proof.

Child, Preschool↗
PubMed1997

Impaired coronary flow reserve in NIDDM: a possible role for diabetic cardiopathy in humans.

Diabetic cardiopathy represents a cardiac disorder with involvement of myocardial, interstitial, coronary, and neural structures. One of the main manifestations refers to coronary microangiopathy, which has not yet been clearly identified. Coronary hemodynamics, including the determination of coronary flow reserve, were therefore analyzed in normal subjects and in nine patients with NIDDM and clinically suspected coronary heart disease but normal coronary arteriogram. Coronary flow reserve was determined as the quotient of baseline and minimal coronary resistance after dipyridamole (0.5 mg/kg i.v.). Coronary blood flow was measured quantitatively by the argon method. Systolic left ventricular function was analyzed by ventriculography and diastolic function by M-mode and Doppler echocardiography. Twelve healthy normotensive subjects served as the control group (CON). In the diabetic patients, maximal coronary flow was significantly reduced (172 +/- 50 vs. 395 +/- 103 ml/min x 100 g; P < 0.001), and minimal coronary resistance was increased (0.60 +/- 0.19 vs. 0.24 +/- 0.06 mmHg x min x 100 g/ml; P < 0.001). Coronary reserve in the diabetic subjects was markedly reduced (1.84 +/- 0.39 vs. 4.23 +/- 0.52; P < 0.001). No difference existed with respect to myocardial oxygen consumption (12.4 +/- 2.3 vs. 11.8 +/- 2.8 ml O2/100 g x min; NS). Global systolic function was normal in all patients (ejection fraction: NIDDM 72 +/- 13 vs. CON 77 +/- 12%, NS; CI: NIDDM 3.2 +/- 0.8 vs. CON 3.3 +/- 1.2 l/min x m2, NS). Diastolic function was impaired in diabetic patients with an increase in relaxation time index (97 +/- 23 vs. 45 +/- 18 ms; P < 0.01) and an impaired diastolic inflow pattern, indicated by the ratio between early and late transmitral flow (0.75 +/- 0.14 vs. 1.66 +/- 0.13; P < 0.05). We conclude that the markedly reduced coronary flow reserve in diabetic patients may play a key role in the induction and perpetuation of coronary insufficiency in myocardial ischemia, in diastolic and systolic dysfunction, and in the initiation of diabetic cardiopathy.

Aged↗
PubMed1997

Oxidative stress and signal transduction.

Reactive oxygen intermediates (ROIs) are an evolutionarily ancient threat to all organisms. Both prokaryotic and higher eukaryotic cells are able to alter their genetic program in response to changes in the intracellular levels of ROIs. In bacteria and yeast, this response leads to the new synthesis of proteins that protect cells from the consequences of oxidative damage, such as DNA strand breaks, lipid peroxidation and oxidative damage of proteins. Intriguingly, higher organisms have also evolved cellular mechanisms to actively produce ROIs. There is increasing evidence that ROIs fulfil an important role as second messengers involved in signal transduction. We have proposed that ROIs have been conserved throughout evolution as universal pathogen messengers turning on genes with important functions in the immune response and cell proliferation. The higher eukaryotic transcription factors NF-kappa B and AP-1 will be described as proteins which are regulated by ROIs under a great variety of pathogenic conditions and initiate the new expression of genes with important roles in immune, inflammatory and other pathogen-related genetic responses.

Humans↗
PubMed1997

[Criteria for successful outcome of external fetal version from breech presentation to cephalic presentation].

The technique of external version of breech presentations has been proposed as a tool to reduce morbidity of fetus and mother. 79 cases of a 3 year period were evaluated aiming at identification of risk factors improving the success rate of the intervention. A total of 48% of attempts was successful. The most frustrating single factor was identified to be the oligohydramnion. Posterior implantation of the placenta improved the rate to 61%. The umbilical cord being localized by coloured Doppler had little influence even if positioned around the neck as neither success nor complications were predictable in this case. Maternal adipositas had a negative influence on the success rate. Perinatal morbidity war not increased in the group of external versions.

Breech Presentation↗
PubMed1996

[Aggressive behavior, increasing loss of independence in mentally retarded patient].

Morbus Wilson is a rare autosomal recessive inborn error of metabolism which leads to an excessive deposition of copper many tissues. There are three types of presentation, an asymptomatic, a hepatic and a neurologic one. In this case report we present a 24-year-old man with mental retardation who showed changes in behaviour and slowness. Clinical and laboratory investigations confirmed the diagnosis of Morbus Wilson. We briefly review typical aspects of this rare disease.

Adult↗
PubMed1996

[Candidiasis of the liver following successful chemotherapy of acute myeloid leukemia (Fab type 6) and recovery with oral fluconazole therapy].

The spectrum of disseminated candidiasis includes both an acute and chronic presentation. In contrast to the acute form, chronic disseminated candidiasis (hepatosplenic candidiasis) often occurs late after granulocytopenic episodes in patients undergoing chemotherapy, usually for acute leukemia. We discuss a female patient who underwent extensive successful chemotherapy for acute myelogenous leukemia (FAB type 6) and who developed chronic hepatosplenic candidiasis 19 months later. Therapy with amphotericin B and flucytosine was not successful and a cure was effected only after long-term oral fluconazole treatment. Diagnostic problems, possible reasons for the observed failure of amphotericin B treatment, and the current use of fluconazole in disseminated candidiasis are discussed.

Aged↗
PubMed1996

The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB.

Opportunistic infections, such as aspergillosis, are among the most serious complications suffered by immunocompromised patients. Aspergillus fumigatus and other pathogenic fungi synthesize a toxic epipolythiodioxopiperazine metabolite called gliotoxin. Gliotoxin exhibits profound immunosuppressive activity in vivo. It induces apoptosis in thymocytes, splenocytes, and mesenteric lymph node cells and can selectively deplete bone marrow of mature lymphocytes. The molecular mechanism by which gliotoxin exerts these effects remains unknown. Here, we report that nanomolar concentrations of gliotoxin inhibited the activation of transcription factor NF-kappaB in response to a variety of stimuli in T and B cells. The effect of gliotoxin was specific because, at the same concentrations, the toxin did not affect activation of the transcription factor NF-AT or of interferon-responsive signal transducers and activators of transcription. Likewise, the activity of the constitutively DNA-binding transcription factors Oct-1 and cyclic AMP response element binding protein (CREB), as well as the activation of protein tyrosine kinases p56lck and p59fyn, was not altered by gliotoxin. Very high concentrations of gliotoxin prevented NF-kappaB DNA binding in vitro. However, in intact cells, inhibition of NF-kappaB did not occur at the level of DNA binding; rather, the toxin appeared to prevent degradation of IkappaB-alpha, NF-kappaB's inhibitory subunit. Our data raise the possibility that the immunosuppression observed during aspergillosis results in part from gliotoxin-mediated NF-kappaB inhibition.

Cells, Cultured↗