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Biomedical subjects

M Hofmann

Publications and source records attributed to M Hofmann.

At least 37 records · Page 2Linked to original sources

Intraoperative radiofrequency maze ablation for atrial fibrillation: the Berlin modification.

BACKGROUND: The Cox-maze procedure combined with an operation for organic heart disease is highly successful in the elimination of chronic atrial fibrillation. However, it prolongs significantly the aortic cross-clamp and operating time. In this study, a simplified left atrial maze procedure, which is a short procedure performed using a surgical radiofrequency ablation probe, is added to elective open heart procedures in patients with atrial fibrillation. METHODS: Forty-eight adults with atrial fibrillation (duration, 6 months to 36 years) underwent elective open heart operations (isolated valve procedures or coronary artery bypass grafting, n = 27 patients; combined procedures, n = 21 patients) combined with intraoperative radiofrequency ablation of the left atrium. The postoperative follow-up period ranged from 1 to 11 months (mean, 4 months). Possible predictors for persistent postoperative atrial fibrillation were determined among 40 variables by univariate and multivariate analyses. RESULTS: Intraoperative radiofrequency ablation prolonged the aortic cross-clamp time for 6 to 14 minutes (mean, 11 minutes). Freedom from atrial fibrillation was 100% intraoperatively, 25% at 1 week after operation (12 of 48 patients), 59% at 1 month postoperatively (16 of 27 patients), 64% at 3 months postoperatively (16 of 25 patients), and 92% at 6 months postoperatively (12 of 13 patients). The only predictor of postoperative atrial fibrillation was the presence of coronary artery disease (odds ratio, 7.5; 80% confidence interval, 2.24-25.13). CONCLUSIONS: Intraoperative radiofrequency ablation of the left atrium combined with an operation for organic heart disease effectively eliminates atrial fibrillation without significant prolongation of the aortic cross-clamp and operative time. The presence of coronary artery disease decreases the success rate during the first 6 postoperative months.

Adult↗

LUV's lipid composition modulates diffusion of bile acids.

Large unilamellar vesicles were prepared from phosphatidylcholine (PC), sphingomyelin (SM), cholesterol (Chol) and cardiolipin (CL) by an extrusion technique (LUVETs). Diffusion of the more hydrophobic lithocholic acid (LCA) and the less hydrophobic chenodeoxycholic acid (CDCA) was investigated by using the pyranine fluorescence method. Membrane permeability was studied by measuring the inclusion of carboxyfluoresceine (CF) into the lipid vesicles, and membrane fluidity was determined with diphenylhexatriene (DPH) and trimethylammonium-diphenylhexatriene (TMA-DPH). All results indicate that, CDCA compared to LCA, exhibits a significantly better penetration into vesicles containing SM. LCA penetrates better into vesicles containing cholesterol. Small amounts of CL influenced the diffusional properties of CDCA more than those of LCA. Since Lamcharfi et al. (1997a) Euro. Biophys. 25, 285-291 have observed differences in the conformational forms of CDCA and LCA in solution, it is suggested that the diffusion rate of bile acids through (model-)membranes is not only dependent on hydrophobicity, but also on bile acid di-(poly-)meric associations and on membrane-lipid composition.

Bile Acids and Salts↗

Effect of alpha-lipoic acid on the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus: an exploratory study.

Oxidative stress plays a central role in the pathogenesis and progression of late microangiopathic complications (diabetic nephropathy) in diabetes mellitus. Previous studies suggested that treatment of diabetic patients with the antioxidant alpha-lipoic acid reduce oxidative stress and urinary albumin excretion. In this prospective, open and non-randomized study, the effect of alpha-lipoic acid on the progression of endothelial cell damage and the course of diabetic nephropathy, as assessed by measurement of plasma thrombomodulin and urinary albumin concentration (UAC), was evaluated in 84 patients with diabetes mellitus over 18 months. Forty-nine patients (34 with Type 1 diabetes, 15 with Type 2 diabetes) had no antioxidant treatment and served as a control group. Thirty-five patients (20 with Type 1 diabetes, 15 with Type 2 diabetes) were treated with 600 mg alpha-lipoic acid per day. Only patients with an urinary albumin concentration <200 mg/l were included into the study. After 18 months of follow up, the plasma thrombomodulin level increased from 35.9+/-9.5 to 39.7+/-9.9 ng/ml (P<0.05) in the control group. In the alpha-lipoic acid treated group the plasma thrombomodulin level decreased from 37.5+/-16.2 to 30.9+/-14.5 ng/ml (P<0.01). The UAC increased in patients without alpha-lipoic acid treatment from 21.2+/-29.5 to 36.9+/-60.6 ng/l (P<0.05), but was unchanged with alpha-lipoic acid. It is postulated that the significant decrease in plasma thrombomodulin and failure of UAC to increase observed in the alpha-lipoic acid treated group is due to antioxidative effects of alpha-lipoic acid, and if so that oxidative stress plays a central role in the pathogenesis of diabetic nephropathy. Furthermore, progression of the disease might be inhibited by antioxidant drugs. A placebo-controlled study is needed.

Albuminuria↗

CD44 is the principal mediator of hyaluronic-acid-induced melanoma cell proliferation.

Interactions of the extracellular matrix component hyaluronic acid and its cellular receptors CD44 and RHAMM/IHABP have been linked to tumor progression and metastasis formation. We investigated the expression and hyaluronic-acid-dependent functions of CD44 and RHAMM/IHABP in human melanoma. Immunohistochemistry of tumor specimens at different stages of melanoma progression revealed an increased expression of CD44 and RHAMM/IHABP. High mRNA expression of CD44 was found in three highly tumorigenic melanoma cell lines compared with less tumorigenic melanoma cells or nontransformed melanocytes. RHAMM/IHABP expression was upregulated in all cell lines analyzed but not in melanocytes. In contrast to the cell surface localization of CD44, RHAMM/IHABP was detected exclusively within the cytoplasm of melanoma cells. Binding and adhesion of melanoma cells to hyaluronic acid is mainly CD44 dependent as it was inhibited to 60%--80% by an anti-CD44 monoclonal antibody whereas anti-RHAMM/IHABP sera had no effect. Culture of melanoma cells in the presence of hyaluronic acid resulted in a dose-dependent, CD44-mediated increase of melanoma cell proliferation and enhanced release of basic fibroblast growth factor and transforming growth factor beta 1. We conclude that (i) the expression of CD44 and RHAMM/IHABP is increased during melanoma progression, (ii) CD44 is the principal hyaluronic acid surface receptor on melanoma cells, and (iii) the hyaluronic-acid-induced increase of the proliferative capacity of melanoma cells is mainly dependent on CD44--hyaluronic acid interactions.

Antigens, Surface↗

[Beyond "successful aging: Rembrandt in his self-portraits].

The process of aging has been generally associated with cognitive dedine. However, some complex cognitive abilities, such as wisdom and judgement, have been suggested to improve with age. In the current study, the development of an advanced artistic ability is examined over the life span of Rembrandt H. van Rijn. Analysis of the paintings revealed the development of an old-age-style in the last portrait, characterised by uniformity of texture, facture, and lighting. The self-portrait painted in the last year of Rembrandt's life reflects a high degree of integration of artistic skill and experience gathered in the course of life, and hence reflects features of wisdom in the sence suggested by Baltes. The development of a mature "late" style can help to characterise the emergence of qualitatively different and advanced cognitive abilities in old age.

Aging↗

[Endometrial carcinoma in patients with diabetes mellitus].

OBJECTIVE: The purposes of this study were to analyze the relationship between clinical and pathological risk factors in endometrial cancer and additional diabetes mellitus and to clarify the correlation between additional diabetes mellitus and survival of patients with this disease. - MATERIAL AND METHODS: This analyze included 181 patients with endometrial carcinoma who were treated between 1985 and 1995 at the University hospital Mainz. Patients with sarcoma were excluded. For statistical analysis a chi(2)-test was performed for univariat analysis. A Kaplan-Meier procedure was performed for over all survival and disease free interval and COX-Regression for multivariate analysis of independence. - RESULTS: The mean follow-up period was 49 months. The mean age was 65 years. 21.8 % of the patients had an additional diabetes mellitus. These patients had a significantly deeper infiltration of the Myometrium (p-value = 0.004) and were more likely to have lymphonode metastasis (p-value = 0.02). - CONCLUSION: Our results show a correlation between Diabetes mellitus and adverse prognostic factors witch affects by the rate of lymphonode spread and overall survival.

Aged↗

Signals from 'crabworld': cuticular reflections in a fiddler crab colony.

Fiddler crabs inhabit intertidal sand- and mudflats, where they live in dense colonies and are active on the surface during low tide. They exhibit a rich behavioural repertoire, with frequent interactions between animals in the context of territorial and mating activities. Male fiddler crabs have one massively enlarged and conspicuously coloured claw, which they use in waving displays and in fights with other males. The crabs carry their eyes on long, vertically oriented stalks high above the body and, as a consequence, see the bodies of conspecifics in the ventral visual field, below the local visual horizon, and against the mudflat surface as background. We filmed events in a colony of Uca vomeris with a normal video camera and an ultraviolet-sensitive camera placed at the eye height of an average crab, approximately 2-3 cm above ground. We also used a spectrographic imager and linear polarized filters to analyse the cues potentially available to the animals for detecting, monitoring and possibly identifying each other. Areas of high contrast in mudflat scenes include specular reflections on the wet cuticle of crabs that are horizontally polarised. Besides specular reflections, some parts of the cuticle generate high-contrast signals against the mudflat background, both at wavelengths between 400 and 700 nm, and in the ultraviolet region between 300 and 400 nm. Uca vomeris can be very colourful: the different parts of the large claw of the male are white, orange or red. The carapace colours of both males and females can range from a mottled yellowish green brown, to a brilliant light blue. White and blue colours contrast starkly with the mudflat background, especially in the ultraviolet wavelengths. Under stress, the blue and white colours can change within minutes to a duller and darker blue or to a dull white.

Animal Communication↗

11 beta-hydroxysteroid dehydrogenase (11 beta-HSD-II) activity in human placenta: its relationship to placental weight and birth weight and its possible role in hypertension.

It has been assumed that low birth weight and high placenta weight were key factors for predicting hypertension in human adulthood. A deficiency in placental 11 beta-HSD-II enzyme activity was supposed to be the underlying cause. To possibly establish 11 beta-HSD-II as a leading factor, we determined 11 beta-HSD-II activities in 133 healthy pregnancies, 21 proteinuric pregnancies complicated by pregnancy-induced hypertension (PIH), 26 non proteinuric PIH pregnancies and 15 pregnancies complicated by fetal growth restriction (32nd-41st gestational week). We could not identify differences in 11 beta-HSD-II activity between pregnancies with the rare combination of small babies with big placentas and others (p = 0.59; Kruskal-Wallis test). And although there was no correlation between 11 beta-HSD-II activity and birth weight, in the control gestational age correlated with 11 beta-HSD-II activity (r = 0.22; p < 0.05; Spearman). 11 beta-HSD-II activity in the proteinuric PIH group was significantly higher than in the controls (11.7 pmol/min/mg prot.; range 10-13.2 vs. 7.9; range 7.0-9.1; p < 0.05). The lowest, but not significant, enzyme activities were in the IUGR group (5.8 pmol/min/mg prot.; range 4.0-9.2). In this group, analysis of variance detected a correlation between enzyme activity and placental weight. In conclusion, we could not confirm that placental 11 beta-HSD-II deficiencies act as an indicator for the risk of adult hypertension in small fetuses with large placentas. However, in growth restriction 11 beta-HSD-II activity might play a role. To clarify the influence in this group, further research is needed. Increased 11 beta-HSD-II activities with gestational age in the control may serve to sustain fetal adrenal steroid genesis and to prepare the fetus for autonomic life.

11-beta-Hydroxysteroid Dehydrogenases↗

Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB.

Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short and transient activation of NF-kappaB in vitro, we observed a long-lasting sustained activation of NF-kappaB in the absence of decreased IkappaBalpha in mononuclear cells from patients with type 1 diabetes. This was associated with increased transcription of NF-kappaBp65. A comparable increase in NF-kappaBp65 antigen and mRNA was also observed in vascular endothelial cells of diabetic rats. As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-beta peptide (Abeta) to the transmembrane receptor for AGE (RAGE) results in protein synthesis-dependent sustained activation of NF-kappaB both in vitro and in vivo. Infusion of AGE-albumin into mice bearing a beta-globin reporter transgene under control of NF-kappaB also resulted in prolonged expression of the reporter transgene. In vitro studies showed that RAGE-expressing cells induced sustained translocation of NF-kappaB (p50/p65) from the cytoplasm into the nucleus for >1 week. Sustained NF-kappaB activation by ligands of RAGE was mediated by initial degradation of IkappaB proteins followed by new synthesis of NF-kappaBp65 mRNA and protein in the presence of newly synthesized IkappaBalpha and IkappaBbeta. These data demonstrate that ligands of RAGE can induce sustained activation of NF-kappaB as a result of increased levels of de novo synthesized NF-kappaBp65 overriding endogenous negative feedback mechanisms and thus might contribute to the persistent NF-kappaB activation observed in hyperglycemia and possibly other chronic diseases.

Adult↗

[Follow-up of differentiated thyroid cancer patients using rhTSH--preliminary results].

AIM: In the follow-up of patients with advanced stage thyroid cancer radioiodine scintigraphy, F-18-FDG PET and tumormarker hTg using stimulation with recombinant human TSH (rhTSH) were compared to the results of same diagnostic procedures during TSH-suppression or endogenous TSH-stimulation. METHODS: 30 patients were investigated in hypothyroidism and after application of rhTSH regarding the serum hormone concentrations, hTg, radioiodine scans and FGD-PET scans. RESULTS: Radioiodine avidity and FDG uptake were significantly higher in 7/30 and 3/5 patients, respectively, compared to endogenous stimulation or TSH-suppression. In about one third of patients hTg increased more than 30%. CONCLUSION: Our preliminary results indicate a sufficient feasibility and sensitivity of rhTSH not only in the follow-up by hTg and radioiodine scan but also in FDG-PET.

Adult↗

PET imaging of somatostatin receptors using [68GA]DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas.

UNLABELLED: Imaging of somatostatin receptors (SSTRs) using [111In]diethylenetriaminepentaacetic-acid-octreotide (DTPAOC) has proven to be helpful in the differentiation of meningiomas, neurinomas or neurofibromas, and metastases as well as in the follow-up of meningiomas. A drawback of the SPECT method is its limited sensitivity in detecting small meningiomas. Because of PET's increased spatial resolution and its ability to absolutely quantify biodistribution, a PET tracer for SSTR imaging would be desirable. METHODS: 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic-acid-D-Phe1-Tyr3-octreotide (DOTATOC) was labeled using the positron-emitting generator nuclide 68Ga. We acquired dynamic PET images over 120 min after intravenous injection of 175 MBq [68Ga]DOTATOC in 3 patients suffering from 8 meningiomas (WHO I degrees; 7- to 25-mm diameter). Patients' heads had been fixed using individually shaped fiber masks equipped with an external stereotactic localizer system to match PET, CT, and MRI datasets. RESULTS: [68Ga]DOTATOC was rapidly cleared from the blood (half-life alpha, 3.5 min; half-life beta, 63 min). Standardized uptake values (SUVs) of meningiomas increased immediately after injection and reached a plateau 60-120 min after injection (mean SUV, 10.6). No tracer could be found in the surrounding healthy brain tissue. All meningiomas (even the 3 smallest [7- to 8-mm diameter]) showed high tracer uptake and could be visualized clearly. Tracer boundaries showed a good correspondence with the matched CT and MRI images. PET provided valuable additional information regarding the extent of meningiomas located beneath osseous structures, especially at the base of the skull. CONCLUSION: According to our initial experiences, [68Ga]DOTATOC seems to be a very promising new PET tracer for imaging SSTRs even in small meningiomas, offering excellent imaging properties and a very high tumor-to-background ratio.

Gallium Radioisotopes↗

Potential live vaccines for HIV.

Potential live vaccines for HIV were developed using an Lpp-OmpA system to target an HIV antigen, reverse transcriptase, or an immunodominant epitope of this enzyme, to the outer membrane of an attenuated strain of Salmonella SL3261. These live vaccines were administered orally to mice, and fecal IgA and helper T cell responses were measured. Results indicated a fecal IgA response specific to HIV reverse transcriptase, as well as a reverse transcriptase-specific helper T cell response, as measured by proliferation assays. Additionally, tests with the epitope vaccines showed a selective cytotoxic CD8 T cell response. These results suggest that this method of antigen targeting to the outer membrane of attenuated bacterial vectors is very promising not only for HIV vaccine development, but also for antigens from other viral or bacterial pathogens, which could be inserted into the Lpp-OmpA protein construct, to elicit mucosal IgA and T cell responses.

AIDS Vaccines↗

Classical swine fever virus: a second ring test to evaluate RT-PCR detection methods.

Six laboratories participated in a study to compare the sensitivity and specificity of RT-PCR tests for the detection of classical swine fever virus (CSFV). Sets of coded samples were prepared by serial dilution of positive samples and then distributed to each of the laboratories. One set comprised 25 samples of random primed cDNA, synthesised from viral RNA representative of different pestiviruses. The other set comprised samples of blood and serum obtained from virus-free or CSFV-infected pigs. Each laboratory tested the samples using PCR/RT-PCR according to a set of standardised protocols that specified the exact conditions and requirements for inclusion of control samples. Two types of test were evaluated. One amplified a part of the 5'-non coding region of the pestivirus genome by means of a closed, one-tube RT-nested PCR. The other amplified a part of the NS5B gene using non-nested RT-PCR. The results of the laboratories were compared with one another, and with those obtained earlier when similar samples were tested by the same laboratories using non-standardised methods [Paton et al., Classical swine fever virus: a ring test to evaluate RT-PCR detection methods, Vet. Microbiol., in press]. Standardisation of the protocols resulted in a more consistent test sensitivity. Three laboratories avoided significant false positive results. Others that did not, could nevertheless recognise that test specificity was inadequate from the results obtained with the control samples. Minimum requirements for the inclusion of adequate controls and periodic proficiency testing are proposed.

Animals↗

Serum iron and ferritin in acute neuroleptic akathisia.

Acute akathisia is a common and disturbing side effect of classic antipsychotic medication. Some evidence suggests a role for iron deficiency in chronic and tardive akathisia. In acute akathisia, however, the data are contradictory. Serum iron and ferritin levels of 33 inpatients with acute akathisia during classic neuroleptic medication were compared with those of 23 patients on classic neuroleptics without this side effect. Akathisia was rated by means of the Hillside Akathisia Scale. The groups were balanced for age (mean 38.5+/-14.5), medication (butyrophenone- and phenothiazine-derived neuroleptics) and diagnosis (schizophrenia, schizoaffective disorder, psychotic affective disorder). Patients with acute akathisia had significantly lower serum ferritin levels than the patients in the control group. However, the ferritin (56. 94+/-39.54 ng/ml) and iron (88.52+/-40.0 mg/dl) levels in these patients were within the normal range (ferritin 30-300 ng/dl, iron 80-180 mg/dl). No correlations between serum iron or ferritin and akathisia ratings could be found. Although some reduction in serum ferritin was found in patients with acute akathisia compared to patients without akathisia, the difference was small and the ferritin levels were within the range of the normal population. These findings suggest a minor role for iron deficiency in acute akathisia.

Adult↗

The structure of arachno-[B6H11]-, at -25 degrees C in (CD3)2O, is resolved via the ab initio/IGLO-GIAO/NMR procedure.

The arachno-[B6H11]- solution structure at -25 degrees C was clarified as fluxional compound 2 by applying the ab initio/IGLO/NMR method. The anion 2 can be derived from arachno-B6H12, 1, by the removal of the B2/B3 bridging hydrogen (2). No minimum on the potential energy surface could be found for an asymmetric complex, a, between [B5H8]- and BH3, which had been proposed originally. A Cs-symmetric [mu-(BH3)B5H8]- complex, A, only 3.2 kcal mol-1 higher in energy than 2, is the intermediate in the fluxional rearrangement observed on the NMR time scale. The transition structure [D] connecting 2 (Erel = 0.0) and A (Erel = 3.2) has a relative energy of 9.7 kcal mol-1. The elimination of both a and A as "most stable structure" candidates of arachno-[B6H11]- reinforces the early geometrical bonding systematics for boranes and carboranes.

Journal Article↗

Orientational ordering of N2O molecules adsorbed on graphite (0001): A novel commensurate pinwheel structure

The structure and orientational ordering of N2O molecules physisorbed on graphite (0001) is investigated applying x-ray, neutron, and low-energy electron diffraction techniques. Combining the results of the three techniques, we find that N2O forms a highly ordered, hexagonal, commensurate (sqrt[21]xsqrt[21])R10.89 degrees phase. The unit cell contains seven molecules which are arranged in a seven-sublattice pinwheel structure, unexpected for linear molecules on a hexagonal lattice. Potential energy calculations corroborate these results.

Journal Article↗

Aerobic training in a patient with nonsevere aplastic anemia: a case report.

This case report examined whether a 26-year-old man with a 5-year history of nonsevere aplastic anemia could perform aerobic training and whether exercise was beneficial. Testing was performed at baseline and at 8 and 16 weeks and included complete blood tests, graded exercise tests with breath-by-breath gas analyses, and health status assessment with the Medical Outcomes Survey SF-12 health survey. Training consisted of treadmill walking for 25 minutes, 3 days a week for 16 weeks, at 75% of maximal heart rate. The patient successfully completed 16 weeks of training and had no adverse effects from testing or training. Training did not produce changes in disease-related measures (hematologic values) or impairment measures (cardiopulmonary measures of fitness). The mental component of the SF-12 improved from below 2 standard deviations from the population mean to within 1 standard deviation of the population mean. The benefits of aerobic training for this person with aplastic anemia were that he showed that he could participate in aerobic-type activities and that training appeared to improve his mental health.

Adult↗