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Biomedical subjects

P Hartmann

Publications and source records attributed to P Hartmann.

At least 19 recordsLinked to original sources

Shear viscosity and shear thinning in two-dimensional Yukawa liquids.

A two-dimensional Yukawa liquid is studied using two different nonequilibrium molecular dynamics simulation methods. Shear viscosity values in the limit of small shear rates are reported for a wide range of Coulomb coupling parameter and screening lengths. At high shear rates it is demonstrated that this liquid exhibits shear thinning; i.e., the viscosity eta diminishes with increasing shear rate. It is expected that two-dimensional dusty plasmas will exhibit this effect.

Journal Article↗

[Clinical pathways--practical aid for the physician? Example: clarification of the suspicion of tuberculosis].

Guidelines, clinical pathways and clinical algorithms are popular instruments nowadays to ensure quality as well as the economic efficiency of medical work. These terms themselves, however, are frequently defined only in a diffuse way. Thus, medical standard procedures often complicate clinical workflows more than to facilitate decision making in everyday life. In our department, feasible standardized approaches have been generated in the form of structured text documents, which on the one hand can aid clinical decision making at the bedside and on the other hand serve as medical sketches for the generation of operational treatment paths on an interdisciplinary level. Structure and content of such an instructional text are exemplified here using our standardized document for the diagnostic approach when tuberculosis is suspected.

Critical Pathways↗

Equilibrium properties and phase diagram of two-dimensional Yukawa systems.

Properties of two-dimensional strongly coupled Yukawa systems are explored through molecular dynamics simulations. An effective coupling coefficient gamma* for the liquid phase is introduced on the basis of the constancy of the first peak amplitude of the pair-correlation functions. Thermodynamic quantities are calculated from the pair-correlation function. The solid-liquid transition of the system is investigated through the analysis of the bond-angular order parameter. The static structure function satisfies consistency relation, attesting to the reliability of the computational method. The response is shown to be governed by the correlational part of the inverse compressibility. An analysis of the velocity autocorrelation demonstrates that this latter also exhibits a universal behavior.

Journal Article↗

TLR-4 surface display on human monocytes is increased in septic patients.

BACKGROUND: Sepsis is a serious condition, most often occurring as a complication of bacterial infections. The Toll-like receptors (TLR)-2 and TLR-4 have been identified as key molecules in response to Gram-positive and Gram-negative bacteria. This study aimed to assess possible alterations of the surface display of TLR-2 and TLR-4 on monocytes and granulocytes derived from patients with sepsis in comparison with healthy controls. - METHODS: We have utilized flow-cytometry to determine the presence of TLR-2 and TLR-4 on the cell surface at baseline and in response to LPS (40 ng/ml) in vitro. - RESULTS: We found no significant differences of TLR-2 display on monocytes and granulocytes from septic patients compared to controls. Surface display of TLR-4 on monocytes from septic patients at baseline was significantly higher than in healthy controls but there was no further response to LPS, whereas controls showed a significant increase of TLR-4 display on the cell surface after LPS stimulation. In contrast, TLR-4 baseline cell surface display on granulocytes was significantly lower in septic patients than in controls and there was no response to LPS in both groups. - CONCLUSION: Our data suggest a complex relationship between TLR-4 display and bacterial challenge in vivo and in vitro.

Adult↗

Incidence and prognosis of CMV disease in HIV-infected patients before and after introduction of combination antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) has improved the prognosis of HIV-infected patients. We studied the changes in the incidence and prognosis of cytomegalovirus (CMV) disease preceding and during the first few years of HAART in a clinic cohort. PATIENTS AND METHODS: All patients with CMV disease diagnosed between 1993 and 1999 from a clinic cohort in Cologne, Germany, were included. The patients were followed until death or until December 31, 2001. The time period from 1993-1996 was classified as pre-HAART, the period from 1997-1999 as the HAART era. Survival was analyzed with a Cox-proportional hazard model. RESULTS: From a total of 1,279 HIV-infected patients, 127 patients with CMV disease were enrolled. The incidence of CMV disease declined rapidly and significantly from 7.34 cases per 100 patient years (py) in the pre-HAART era to 0.75 cases per 100 py in the HAART era. The median survival time in the pre-HAART era was 9.5 months; the median survival was not yet reached at 4 years of follow-up in the HAART era. The only risk factors influencing survival were CD4-cell count and antiretroviral therapy before and after diagnosis of CMV disease. Treatment naive patients had a better prognosis than pretreated patients and patients treated with triple combination therapy survived longer than patients with other treatment modalities. CONCLUSION: A rapid decline in the incidence of new CMV manifestations and a better prognosis of patients with CMV disease, especially if they were treatment naive and treated with triple combination therapy, were observed in the HAART era.

AIDS-Related Opportunistic Infections↗

Cytokine and nitric oxide responses of monocyte-derived human macrophages to microsporidian spores.

Microsporidia are obligate intracellular parasites that emerged as opportunistic pathogens since the onset of the AIDS pandemic. They are capable of disseminating through the body using macrophages as vehicles. We incubated human macrophages with spores of all three Encephalitozoon spp. as well as with Vittaforma corneae, and the number of intracellular spores per cell was determined by fluorescence microscopy. Cell culture supernatants were collected and the content of TNF-alpha, INF-gamma, IL-10, and of nitric oxide was determined. Microsporidian spores did not induce a nitric oxide response in macrophages and there was a negative correlation between the number of intracellular spores and the amount of nitric oxide. TNF-alpha, INF-gamma, and IL-10 increased after simulation of macrophages with microsporidian spores but for TNF-alpha and INF-gamma no clear correlation of cytokine levels with the number of intracellular spores could be observed. A modulation of the nitric oxide response by intracellular microsporidia may contribute to the survival of microsporidia within the macrophage by a mechanism yet unknown.

Animals↗

Cell invasion and intracellular fate of Encephalitozoon cuniculi (Microsporidia).

Microsporidia are obligate intracellular parasites that utilize a unique mechanism to infect host cells, which is one of the most sophisticated infection mechanisms in biology. Microsporidian spores contain a long coiled polar tube that extrudes from the spores and penetrates the membranes of new host cells. We have initiated a study to investigate the invasive process and intracellular fate of the microsporidium Encephalitozoon cuniculi. Here we show that relatively few cells were infected through the traditional penetration of the polar tube from outside. Rather, phagocytosis of spores occurred at least 10 times more frequently than injection of sporoplasms. Some spores extruded their polar tube inside the cells following phagocytosis. Membranes of the vacuoles surrounding the internalized spores were positive for late endosomal and lysosomal markers. Spores that remained inside these compartments disappeared within 3 days. Thus, our studies demonstrate that in addition to the unique way in which microsporidia infect host cells, E. cuniculi spores can also gain access to host cells by phagocytosis. The presence of intracellular spores that have extruded their polar tube shows that some spores germinate after phagocytosis, thus escaping from the phagosomes that mature into lysosomes.

Animals↗

Collective modes of quasi-two-dimensional Yukawa liquids.

Particles in dusty plasmas are often confined to a quasi-two-dimensional arrangement. In such layers--besides the formation of compressional and (in-plane) shear waves--an additional collective excitation may also show up, as small-amplitude oscillations of the particles perpendicular to the plane are also possible. We explore through molecular dynamics simulations the properties (fluctuation spectra, dispersion relation, Einstein frequency) of this out-of-plane transverse mode in the strongly coupled liquid phase of Yukawa systems.

Journal Article↗

Nicotinic receptor mediated stimulation of NO-generation in neurons of rat thoracic dorsal root ganglia.

The contribution of nicotinic acetylcholine receptors (nAChRs) to stimulation of NO-production was investigated in isolated rat dorsal root ganglion (DRG) neurons utilizing an NO-sensitive fluorescent indicator 4,5-diaminofluorescein-diacetate (DAF-2DA) and appropriate channel blockers. RT-PCR and immunohistochemical analysis of NOS isoforms in cultured neurons revealed the expression of eNOS in the vast majority of neurons, nNOS in about 5-10%, and iNOS only exceptionally. Application of nicotine resulted in an abrupt increase in DAF-2T fluorescence in 65% of neuronal cell bodies that was fully sensitive to the general nAChR antagonist mecamylamine. Methyllycaconitine reduced the number of nicotine-sensitive neurons and the extent of NO-generation. Thus, alpha7- and/or alpha9/10-nAChRs are required for nicotine-induced NO-production in a subpopulation of DRG neurons, and appear to be partially involved in the remaining, larger subpopulation.

Animals↗

Two-dimensional Yukawa liquids: correlation and dynamics.

A combined theoretical and molecular dynamics (MD) simulation study of the collective modes and their dispersion in a two-dimensional Yukawa system in the strongly coupled liquid state is presented. The theoretical analysis relies upon the quasilocalized charge approximation; the MD simulation generates static pair correlation functions and dynamical current-current correlation spectra.

Journal Article↗

Thermal conductivity of strongly coupled Yukawa liquids.

The thermal conductivity of strongly coupled Yukawa liquids, being relevant to dusty plasmas, is calculated from nonequilibrium molecular dynamics simulations. The calculations cover a wide range of plasma coupling (Gamma) and screening (kappa) parameters and yield data which are generally in good agreement with the results of recent independent calculations. An improved analytical formula, relating the thermal conductivity to the reduced temperature and to the screening length, is proposed.

Journal Article↗

Unusual and severe symptomatic impairment of neutrophil function after one cycle of temozolomide in patients with malignant glioma.

Temozolomide, a recently approved cytotoxic agent for the treatment of malignant glioma, has shown promising results in the treatment studies published so far. However, cytopenia and related infectious complications have been reported in 2-8% of cases. Here we present three treatment-naive patients with malignant glioma experiencing cytopenia and/or infectious complications after the first cycle of temozolomide. Neutrophils obtained from each patient up to 6 weeks after the end of the temozolomide application showed normal phagocytic capacity but decreased oxygen radical production and thus impairment of microcidal activity. Our data suggest that a prolonged impairment of the immunological defense may occur in temozolomide-treated patients.

Antineoplastic Agents, Alkylating↗

Dynamical structure functions, collective modes, and energy gap in charged-particle bilayers.

The dynamical properties of strongly coupled charged-particle bilayers are investigated by molecular dynamics (MD) simulation and theoretical analysis. The spectra of the current correlation functions show the existence of two (in-phase and out-of-phase) longitudinal and two (in-phase and out-of-phase) transverse collective modes. The out-of-phase modes possess finite frequencies at wave numbers k-->0, confirming the existence of the predicted long-wavelength energy gap in the bilayer system. A theoretical model based on an extended Feynman ansatz for the dynamical structure functions provides predictions on the strength of the collective modes that are verified by the MD experiment.

Journal Article↗

BEACOPP therapeutic regimen for patients with Hodgkin's disease and HIV infection.

BACKGROUND: Hodgkin's disease (HD) is the most common non-AIDS-defining tumor diagnosed in HIV-infected patients. Antineoplastic treatment is difficult considering the underlying immunodeficiency caused by HIV itself and may increase the risk of opportunistic infections. The purpose of this study was to evaluate the efficacy and safety of the chemotherapeutic regimen bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) in HIV-infected patients with HD (HIV-HD). PATIENTS AND METHODS: Twelve patients with HIV-HD were scheduled to receive six cycles of BEACOPP. Five patients received concomitant antiretroviral therapy. Two patients received additional radiotherapy. Restaging was carried out after three and six cycles of chemotherapy. CD4 counts and HIV RNA levels were regularly monitored during the course of chemotherapy. RESULTS: Complete remission (CR) was achieved in all patients. Of 12 patients, eight patients received the intended six cycles of BEACOPP. Two patients died of opportunistic infections within the treatment period, one patient died of a relapse after 26 months. The other nine patients remain in CR for their individual follow-up period, median 49 months (range 13-108). The most commonly observed toxicity was bone marrow suppression with National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3/4 leukopenia in 75% of all cases. The mean decline of CD4+ lymphocytes was 238 +/- 230/ micro l, with a mean recovery of 272 +/- 329/ micro l 6 months after the last cycle. Plasma levels of HIV RNA increased moderately or even declined under chemotherapy if highly active anti-retroviral therapy was given concomitantly with BEACOPP. CONCLUSIONS: The BEACOPP regimen is feasible and highly effective in HIV-HD patients. With respect to its overall moderate toxicity, BEACOPP is a safe regimen even in the immunocompromised patient.

AIDS-Related Opportunistic Infections↗

Capacitive-coupling-enhanced switching gain in an electron y-branch switch.

We have fabricated electron Y-branch switches (YBS) on modulation doped GaAs/AlGaAs heterostructures. The Y branch consists of a one-dimensional source, which is split along the branching section into two one-dimensional drains. In addition to source drain voltages, external electric fields can be applied via gates along the branches. In the nonlinear transport regime sweeps of the side-gate voltages lead to a voltage difference between the drain reservoirs with gain. This switching gain increases superlinearly with the bias voltage applied between the source and the drains of the YBS. We explain the bias voltage enhanced switching by a capacitive coupling of the branches.

Journal Article↗

Randomized controlled monocentric comparison of once daily ceftriaxone with tobramycin and cefotaxime three times daily with tobramycin in neutropenic fever.

A prospective, randomized, controlled monocentric trial was performed to evaluate the efficacy and safety of once daily ceftriaxone 2 g plus tobramycin 5 mg/kg in comparison to cefotaxime 2 g t.i.d. plus tobramycin 5 mg/kg qd in the treatment of neutropenic fever. In cases of fever > or = 38.5 degrees C and a neutrophil count below 1000/microliter, patients with hematological malignancies were assigned to ceftriaxone or cefotaxime, each with tobramycin. The primary endpoint was defined as defervescence < 37.5 degrees C on day 4-6 followed by at least 7 afebrile days. Secondary endpoints were overall response, defined as defervescence on day 25 and toxicity. There were 160 episodes of 114 patients included. Fever of unknown origin accounted for 79 episodes (51%), microbiologically defined infection for 36 (23%), clinically defined infection for 27 (17%), and both clinically and microbiologically defined infection for 14 episodes (9%). On an intent-to-treat basis 156 episodes could be evaluated for the primary endpoint. Ceftriaxone plus tobramycin and cefotaxime plus tobramycin resulted in a primary response in 46.9% and 45.3%, respectively. Overall response was achieved on study day 25 in 87.7% and 80%, respectively. No significant difference in toxicity was observed. Once-daily ceftriaxone plus tobramycin was not inferior to cefotaxime t.i.d. plus tobramycin qd in the empirical treatment of neutropenic fever.

Adult↗

[Population-based study of diabetic retinopathy in Wolfsburg].

INTRODUCTION: Since November 1997 the complete documentation of an ophthalmological examination of diabetics has been annually subsidized by the Volkswagen Corporation Health Maintenance Organization (VW-HMO). METHODS: The results of an annual ophthalmological examination were recorded in a standardised history sheet developed by the Initiative Group for Early Detection of Diabetic Eye Diseases. These data included visual acuity, intraocular pressure, lens status and a description of fundus abnormalities. RESULTS: Within 26 months ophthalmological examinations of 2,801 patients were completed which represented 4.5% of all VW-HMO insured patients. On average, patients suffered from diabetes for 9.6 years (SD +/- 8.3), artificial intraocular lenses were present in 357 eyes (6.4%) and 1,216 eyes (12.0%) were diagnosed with cataract or posterior capsule opacification impairing visual acuity. Out of 263 patients younger than 40 years old, 18.8% had a mild or moderate and 3.3% a severe non-proliferative diabetic retinopathy (NPDR). A proliferative diabetic retinopathy (PDR) was found in 2.2% of the younger patients. Of 2,228 patients aged 40 years and older, 11.9% had a mild or moderate and 2.6% a severe NPDR. In 0.9% of this group PDR was diagnosed. CONCLUSIONS: An annual ophthalmological screening based on a survey sheet of the Initiative Group was successfully introduced. For the first time a population-based evaluation on the prevalence of diabetic retinopathy was carried out for inhabitants of a German city. The prevalence of PDR was found to be lower than previously published in comparable studied.

Adolescent↗