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Biomedical subjects

M Hartmann

Publications and source records attributed to M Hartmann.

At least 73 records · Page 4Linked to original sources
PubMed2002

Dermatological diseases and signs of HIV infection.

Therapy of HIV infection has undergone significant changes since the introduction of highly-active antiretroviral therapy (HAART). Mortality and the appearance of opportunistic infections have significantly been reduced. Diseases of the skin and adjacent mucous membranes often provide the first signs for HIV infection. The spectrum of dermatologic findings related to HIV includes a variety of cutaneous and mucocutaneous disorders. The most frequent diagnoses are oral candidiasis, mollusca contagiosa, oral hairy leuokoplakia, herpes zoster and herpes simplex, seborrheic dermatitis, and Kaposi's sarcoma. Incompatibility reactions to drugs are observed on a strikingly frequent basis in HIV infection. Such severe incompatibility reactions are much more frequent in HIV patients than in the normal population. Inducers often include sulfonamides, cotrimoxazole, tuberculostatics as well as nucleoside-type reverse transcriptase inhibitors.

Drug Eruptions↗
PubMed2002

Evolution of gas-filled nanocracks in crystalline solids.

In this work, the evolution of gas-filled cracks under gas implantation and subsequent annealing is studied on the basis of an elastic continuum approach. The observed growth limitation of He-filled nanocracks in SiC is attributed to their stabilization by the formation of circular dislocation dipoles. The formation and Ostwald ripening of bubble-loop complexes at elevated temperatures is modeled in terms of gas atom exchange between such complexes coupled with local matrix atom exchange between bubbles and loops of the same complex. The scaling laws derived for the time dependence of bubble and loop sizes are found to be in good agreement with experimental data.

Journal Article↗
PubMed2002

Correlations between light penetration into skin and the therapeutic outcome following laser therapy of port-wine stains.

For several years the flashlamp-pumped pulsed dye laser (FPDL) has been the favoured method for the treatment of port-wine stains (PWS). The therapeutic outcome of FPDL laser therapy depends on the anatomical location of the PWS and is mainly attributed to morphological parameters such as size and depth of the PWS blood vessels. The aim of this study was to show a correlation between the therapeutic outcome following FPDL therapy and the optical properties of the skin overlying the PWS vessels. For this purpose the therapeutic outcome following FPDL treatment (585 nm; 0.45 ms) of 884 PWS situated on different body sites was evaluated by judging the grade of fading of PWS colour. On the other hand the light penetration into 123 skin samples (thickness 0.10-1.35 mm) was determined between 450 nm and 1030 nm and compared with the PWS laser therapy outcome for equal locations by statistical analysis. PWS on the neck, trunk, arms or legs yielded a higher mean grade of fading as compared to PWS on the head. Within the face, a wide range of fading was evident. The light penetration into skin increased linearly with increasing wavelength and location-dependent differences were found. The attenuation coefficient was 22.8+/-5.3 mm(-1) at 585 nm. No significant or strong correlation was observed between the therapeutic outcome of PWS laser therapy and the light penetration into skin. However, a correlation was obvious by plotting the respective profile plots. Therefore, among other effects, in particular morphological parameters of PWS vessels, the optical properties of the skin contribute to a small extent to the clinical outcome of PWS laser therapy.

Adolescent↗
PubMed2002

[Is there a temporal correlation between substance abuse and psychosis in adolescents?].

OBJECTIVES: The temporal relationship between substance abuse and symptoms of psychosis in adolescent patients was examined. METHODS: The hospital records of all adolescent inpatients admitted to the Central Institute of Mental Health in Mannheim during the period from 1976-1997 with a first-time diagnosis of psychosis were examined retrospectively for evidence of co-morbid substance abuse. RESULTS: In 18 of a total of 165 psychotic patients, co-morbid substance abuse was present, whose frequency rose after 1988, with a renewed increase since 1996. Two of the 18 adolescents began taking drugs only after the appearance of the first symptoms of psychosis, in 13 others the abuse was already well established, while for the final three patients the onset of psychotic symptoms and substance abuse was congruent, occurring within the same month. A close temporal correlation between symptoms of psychosis and substance abuse was established for amphetamines (including ecstasy), LSD and excessive abuse of cannabis. CONCLUSIONS: Substance abuse constitutes a risk factor for the development of psychoses without, however, necessarily being a direct trigger of psychosis.

Adolescent↗
PubMed2002

Elevated expression of extracellular matrix metalloproteinase inducer (CD147) and membrane-type matrix metalloproteinases in venous leg ulcers.

BACKGROUND: Matrix metalloproteinases (MMPs) contribute to matrix remodelling in venous leg ulcers. Extracellular MMP inducer (EMMPRIN; CD147) has been reported to increase MMP expression, and membrane type 1 MMP (MT1-MMP) has been implicated in the activation of MMPs. OBJECTIVES: To examine whether and to what degree EMMPRIN, MMP-2, MT1-MMP and membrane type 2 MMP (MT2-MMP) are expressed in venous leg ulcers as well as the association with MMP activity. METHODS: EMMPRIN, MMP-2, MT1-MMP and MT2-MMP were analysed by zymography and immunohistochemistry in biopsies from healthy skin and lesional tissue from venous leg ulcers. RESULTS: Zymography provided direct evidence of increased proteolytic activity of MMP-2 in lesional skin in comparison with healthy controls. Immunostaining showed intense expression of EMMPRIN, MMP-2, MT1-MMP and MT2-MMP in dermal structures of venous leg ulcers, whereas only EMMPRIN and MMP-2 showed elevated expression in perivascular regions. Our findings indicate that venous leg ulcers are characterized by elevated expression of EMMPRIN, MMP-2, MT1-MMP and MT2-MMP. The immunohistological findings of skin alterations reflect the dynamic process of activation of soluble and membrane-bound MMPs, which may be highly induced by EMMPRIN. CONCLUSIONS: These data suggest for the first time that membrane-bound MMPs may favour enhanced turnover of the extracellular matrix and support unrestrained MMP activity in venous leg ulcers.

Antigens, CD↗
PubMed2002

[Functional MRI procedures in the diagnosis of brain tumors: Perfusion- and diffusion-weighted imaging].

Despite the increased diagnostic accuracy of contrast material enhanced MR imaging, specification and grading of brain tumors are still only approximate at best: neither morphology, nor relaxation times or contrast material enhancement reliably predict tumor histology or tumor grade. As histology and tumor grade strongly influence which therapy concept is chosen, a more precise diagnosis is mandatory. With diffusion- and perfusion-weighted MR imaging (DWI, PWI) it is now possible to obtain important information regarding the cellular matrix and the relative regional cerebral blood volume (rrCBV) of brain tumors, which cannot be obtained with standard MR techniques. These dynamic-functional imaging techniques are very useful in the preoperative diagnosis of gliomas, lymphomas, and metastases, as well as in the differentiation of these neoplastic lesions from abscesses, atypical ischemic infarctions, and tumor-like manifestations of demyelinating disease. Additionally, they appear suitable for determining glioma grade and regions of active tumor growth which should be the target of stereotactic biopsy and therapy. After therapy these techniques are helpful to better assess the tumor response to therapy, possible therapy failure and therapy complications such as radiation necrosis.

Biopsy↗
PubMed2002

CT and diffusion-weighted MR imaging in randomized order: diffusion-weighted imaging results in higher accuracy and lower interrater variability in the diagnosis of hyperacute ischemic stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted MRI (DWI) has become a commonly used imaging modality in stroke centers. The value of this method as a routine procedure is still being discussed. In previous studies, CT was always performed before DWI. Therefore, infarct progression could be a reason for the better result in DWI. METHODS: All hyperacute (<6 hours) stroke patients admitted to our emergency department with a National Institutes of Health Stroke Scale (NIHSS) score >3 were prospectively randomized for the order in which CT and MRI were performed. Five stroke experts and 4 residents blinded to clinical data judged stroke signs and lesion size on the images. To determine the interrater variability, we calculated kappa values for both rating groups. RESULTS: A total of 50 patients with ischemic stroke and 4 patients with transient symptoms of acute stroke (median NIHSS score, 11; range, 3 to 27) were analyzed. Of the 50 patients, 55% were examined with DWI first. The mean delay from symptom onset until CT was 180 minutes; that from symptom onset until DWI was 189 minutes. The mean delay between DWI and CT was 30 minutes. The sensitivity of infarct detection by the experts was significantly better when based on DWI (CT/DWI, 61/91%). Accuracy was 91% when based on DWI (CT, 61%). Interrater variability of lesion detection was also significantly better for DWI (CT/DWI, kappa=0.51/0.84). The assessment of lesion extent was less homogeneous on CT (CT/DWI, kappa=0.38/0.62). The differences between the 2 modalities were stronger in the residents' ratings (CT/DWI: sensitivity, 46/81%; kappa=0.38/0.76). CONCLUSIONS: CT and DWI performed with the same delay after onset of ischemic stroke resulted in significant differences in diagnostic accuracy. DWI gives good interrater homogeneity and has a substantially better sensitivity and accuracy than CT even if the raters have limited experience.

Acute Disease↗
PubMed2002

Sexually transmitted diseases in Germany.

In the former West Germany, in specific venereal diseases legislation passed in 1953, only syphilis, gonorrhoea, ulcus molle, and lymphogranuloma venereum were defined as venereal diseases and subject to mandatory notification. The proportion of unreported cases was as high as 75% for syphilis and up to 90% for gonorrhoea. Epidemiological data for the past 10 years exist only on selected populations from research studies and are summarized in this article. In the former East Germany reporting of sexually transmitted infections (STIs) was mandatory and, due to the centralized organization, underreporting was considered to be low, although no specific studies have examined this. After the unification in 1990 of the two German states the West German laws were adopted in East Germany. Since 1982 - when the first AIDS case was reported in Germany - information on AIDS cases has voluntarily been collected at the national register at the AIDS Centre of the Robert Koch Institute in Berlin. The law governing the reporting of infectious diseases has recently been revised. Under the new Protection against Infection Act, which became effective on 1 January 2001, clinical diagnoses of STIs (with the exception of hepatitis B) are no longer notifiable diseases. Laboratory reporting of positive test results for Treponema pallidum has been introduced. With T. pallidum and HIV notifications, additional disaggregated data are collected. Since T. pallidum and HIV remain the only notifiable STIs, all other STIs have to be monitored through sentinel surveillance systems. These surveillance systems are currently being established. Under the new legislation, local health authorities have to provide adequate counselling and testing services for STIs, which may be provided free of charge if necessary.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Electronic signature for medical documents--integration and evaluation of a public key infrastructure in hospitals.

OBJECTIVES: Our objectives were to determine the user-oriented and legal requirements for a Public Key Infrastructure (PKI) for electronic signatures for medical documents, and to translate these requirements into a general model for a signature system. A prototype of this model was then implemented and evaluated in clinical routine use. METHODS: Analyses of documents, processes, interviews, observations, and of the available literature supplied the foundations for the development of the signature system model. Eight participants of the Department of Dermatology of the Heidelberg University Medical Center evaluated the implemented prototype from December 2000 to January 2001, during the course of an intervention study. By means of questionnaires, interviews, observations and database analyses, the usefulness and user acceptance of the electronic signature and its integration into electronic discharge letters were established. RESULTS: Since the major part of medical documents generated in a hospital are signature-relevant, they will require electronic signatures in the future. A PKI must meet the multitude of responsibilities and security needs required in a hospital. Also, the signature functionality must be integrated directly into the workflow surrounding document creation. A developed signature model, fulfilling user-oriented and legal requirements, was implemented using hard and software components that conform to the German Signature Law. It was integrated into the existing hospital information system of the Heidelberg University Medical Center. At the end of the intervention study, the average acceptance scores achieved were mean = 3.90; SD = 0.42 on a scale of 1 (very negative attitude) to 5 (very positive attitude) for the electronic signature procedure. Acceptance of the integration into computer-supported discharge letter writing reached mean = 3.91; SD = 0.47. On average, the discharge letters were completed 7.18 days earlier. CONCLUSION: The electronic signature is indispensable for the further development of electronic patient records. Application-independent hard and software components, in accordance with the signature law, must be integrated into electronic patient records, and provided to certification services using standardized interfaces. Signature-oriented workflow and document management components are essential for user acceptance in routine clinical use.

Authorship↗
PubMed2001

Reduced number of functional glutamatergic synapses in hippocampal neurons overexpressing full-length TrkB receptors.

Brain-derived neurotrophic factor (BDNF) acutely modulates the efficacy of central glutamatergic synapses via activation of the receptor tyrosine kinase TrkB. On a longer time scale, recent evidence suggests an additional role of TrkB signaling in the formation of excitatory synaptic connections. Here, we have overexpressed full-length TrkB receptors (fl-TrkB) in hippocampal neurons, to investigate the contribution of BDNF signaling to the maturation of glutamatergic synapses. Using patch clamp recordings, we show a three-fold reduction in glutamatergic excitatory autaptic and synaptic current amplitudes in neurons overexpressing fl-TrkB, and application of saturating concentrations of BDNF and NT-4/5 completely reverses this effect. Compatible with these overexpression data, in untransfected neurons, scavenging of endogenous BDNF and NT-4/5 by TrkB-IgGs reduces excitatory autaptic current (EAC) amplitudes. By overexpression of truncated TrkB receptors (TrkB.T1, TrkB.T2) and a chimeric receptor containing only the intracellular domain of fl-TrkB, we show that intra- and extracellular domains of fl-TrkB are necessary to observe the EAC reduction. Labeling of presynaptic terminals with FM 4-64 revealed, that the reduced EAC amplitudes in fl-TrkB overexpressing neurons are accompanied by a two-fold reduction in synapse number. These results suggest, that ligand-independent signaling through fl-TrkB receptors can decrease glutamatergic synaptic strength, if sufficient amounts of BDNF or NT-4/5 are not available.

Aging↗
PubMed2001

Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses.

The protein brain-derived neurotrophic factor (BDNF) has been postulated to be a retrograde or paracrine synaptic messenger in long-term potentiation and other forms of activity-dependent synaptic plasticity. Although crucial for this concept, direct evidence for the activity-dependent synaptic release of BDNF is lacking. Here we investigate secretion of BDNF labelled with green fluorescent protein (BDNF-GFP) by monitoring the changes in fluorescence intensity of dendritic BDNF-GFP vesicles at glutamatergic synaptic junctions of living hippocampal neurons. We show that high-frequency activation of glutamatergic synapses triggers the release of BDNF-GFP from synaptically localized secretory granules. This release depends on activation of postsynaptic ionotropic glutamate receptors and on postsynaptic Ca(2+) influx. Release of BDNF-GFP is also observed from extrasynaptic dendritic vesicle clusters, suggesting that a possible spatial restriction of BDNF release to specific synaptic sites can only occur if the postsynaptic depolarization remains local. These results support the concept of BDNF being a synaptic messenger of activity-dependent synaptic plasticity, which is released from postsynaptic neurons.

Animals↗
PubMed2001

Pi-donation and stabilizing effects of pnicogens in carbenium and silicenium ions: a theoretical study of [C(XH2)3]+ and [Si(XH2)3]+ (X = N, P, As, Sb, Bi).

Quantum chemical calculations at the MP2 and CCSD(T) levels of theory are reported for cations of the general type [A(XH2)3]+ with A = C, Si and X = N, P, As, Sb, Bi. Population analysis, methyl stabilization energies (MSEs), and structural criteria were used to predict the p(pi)-donor ability of and the pi-stabilization energy exerted by this series of pnicogens. All of the substituents XH2 considered in these studies invariably stabilize the triply substituted carbenium as well as the silicenium ions. The calculated data show that the intrinsic p(pi)-donation of the group 15 atoms follows the order N < P < As < Sb < Bi. However, the trend of the stabilization energies is fully reversed. The intrinsic stabilization energies of the planar carbenium ions decrease monotonically from 161.2 kcal mol(-1) for X = NH2 to 98.0 kcal mol(-1) for X = BiH2. The effective stabilization of the pnicogens in the equilibrium structures, which also includes the energy-demanding pyramidalization of the XH2 substituents, follows the same trend, although the absolute numbers are reduced to 145.6 kcalmol(-1) for X = NH2 and 53.2 kcalmol(-1) for X = BiH2. This seemingly contrasting behavior of increasing p(pi) charge donation and decreasing stabilization has already been found for other substituents. Previous studies have shown that carbenium ions substituted by chalcogens up to the fourth row also stabilize C+ less effectively with respect to heavier substituents. Of the ions investigated in this study, only the silicenium ions that are stabilized by pnicogens from the third to the sixth row of the periodic system yield increased stabilizing energies that follow the corresponding intrinsic p(pi)-donor abilities of the respective substituent.

Journal Article↗
PubMed2001

Hydrophobic forms of morphine-6-glucosides.

NMR spectroscopy of 6-acetylmorphine (6-AM), a chloroform-soluble model compound for the hydrophilic, highly potent analgesic drug morphine-6-glucoronide (M6G), in a hydrophobic solvent indicates one hydrogen bonded water molecule per molecule of 6-AM. By analysis of nuclear Overhauser enhancements (NOEs) we find a 6-AM dimer in which the monomers are linked by two water molecules. Molecular modeling studies underscore the stability of such dimeric structures involving water molecules for 6-AM and point out their more lipophilic character allowing penetration of the blood-brain barrier.

Dimerization↗
PubMed2001

The catalytic activities of the bifunctional Azotobacter vinelandii mannuronan C-5-epimerase and alginate lyase AlgE7 probably originate from the same active site in the enzyme.

The Azotobacter vinelandii genome encodes a family of seven secreted Ca(2+)-dependent epimerases (AlgE1--7) catalyzing the polymer level epimerization of beta-D-mannuronic acid (M) to alpha-L-guluronic acid (G) in the commercially important polysaccharide alginate. AlgE1--7 are composed of two types of protein modules, A and R, and the A-modules have previously been found to be sufficient for epimerization. AlgE7 is both an epimerase and an alginase, and here we show that the lyase activity is Ca(2+)-dependent and also responds similarly to the epimerases in the presence of other divalent cations. The AlgE7 lyase degraded M-rich alginates and a relatively G-rich alginate from the brown algae Macrocystis pyrifera most effectively, producing oligomers of 4 (mannuronan) to 7 units. The sequences cleaved were mainly G/MM and/or G/GM. Since G-moieties dominated at the reducing ends even when mannuronan was used as substrate, the AlgE7 epimerase probably stimulates the lyase pathway, indicating a complex interplay between the two activities. A truncated form of AlgE1 (AlgE1-1) was converted to a combined epimerase and lyase by replacing the 5'-798 base pairs in the algE1-1 gene with the corresponding A-module-encoding DNA sequence from algE7. Furthermore, substitution of an aspartic acid residue at position 152 with glycine in AlgE7A eliminated almost all of both the lyase and epimerase activities. Epimerization and lyase activity are believed to be mechanistically related, and the results reported here strongly support this hypothesis by suggesting that the same enzymatic site can catalyze both reactions.

Amino Acid Sequence↗
PubMed2001

Successful treatment of aids related PML with HAART and cidofovir.

Progressive multifocal leukoencephalopathy (PML) is a progressive demyelinating infection of the central nervous system caused by the JC virus (JCV) in an advanced state of the acquired immunodeficiency syndrome (AIDS). Currently there are still no drugs with proven clinical efficacy against JCV, though highly active antiretroviral therapy (HAART) and the associated partial immune reconstitution have a beneficial effect on the survival time of AIDS-related PML. Various case reports have described an acceptable response under treatment with cidofovir which may be of particular benefit if HAART does not result in sufficient immune reconstitution. We report a patient with AIDS-related PML who improved under combined therapy with HAART and cidofovir. This suggests that the immediate combination of both drugs further improves the outcome of AIDS-related PML.

AIDS-Related Opportunistic Infections↗
PubMed2001

Up-regulation of cyclin-dependent kinase 4/cyclin D2 expression but down-regulation of cyclin-dependent kinase 2/cyclin E in testicular germ cell tumors.

Testicular germ cell tumors (GCT) characteristically display two chromosome 12 abnormalities: the isochromosome i(12p) and concomitant deletions of the long arm. Some genes important in the control of the G(1)-S cell cycle checkpoint G(1)-S, i.e., cyclin-dependent kinases 2 and 4, cyclin D2 are located on this chromosomal region. Therefore, testicular GCTs were analyzed as to the expression of CDK2, CDK4, CDK6, and the expression of their catalytic partners cyclins D1, D2 and E by semiquantitative reverse transcription-PCR. Cyclin D2, located on 12p, was overexpressed in 69% (31 of 45) of the tumors by a mean factor of 8, including all histological subtypes. In addition, the cyclin D2 partner CDK4 was increased in 41% (21 of 51) of all tumors by a factor of 6, most strongly in embryonal carcinomas. Sixty-four percent of the seminomas and 23% of the non-seminomas had decreased expression of CDK6 by a mean factor of 5 (P = 0.009). Statistical analysis using configural frequency analysis and regression analysis revealed that cyclin D2 and CDK4 expression were strongly correlated (r(2) = 0.682; P = 0.000052), whereas expression of CDK6 did not correlate with either of them (r(2) = 0.382; P = 0.00085). CDK2 and its catalytic partner cyclin E were down-regulated in 40% (19 of 47) and 42% (19 of 45) of the tumors, respectively, by a factor of 7 each. Western blots and immunohistochemical experiments confirmed cyclin D2 and CDK4 overrepresentation and reduced expression of cyclin E and CDK2 tumors in the few tumors under protein study. Despite its localization on 12q13, a hot spot for loss of heterozygosity in testicular GCTs (>40%), Southern blotting revealed no gross DNA alteration of the CDK2 gene. Because up-regulation of the cyclin D2/CDK4 complex and down-regulation of cyclin E/CDK2 complex were found in seminomas as well as in non-seminomas and in all tumor stages, these findings seem to be early events during tumorigenesis of testicular GCTS: Together with previous findings that retinoblastoma mRNA and protein expression is strongly decreased in these tumors, these data suggest an unusual deregulated G(1)-S checkpoint as a decisive event for germ cell tumors.

CDC2-CDC28 Kinases↗