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Biomedical subjects

F Albert

Publications and source records attributed to F Albert.

At least 19 recordsLinked to original sources

Coherence-based transverse measurement of synchrotron x-ray radiation from relativistic laser-plasma interaction and laser-accelerated electrons.

We observe Fresnel edge diffraction of the x-ray beam generated by the relativistic interaction of a high-intensity laser pulse with He gas. The observed diffraction at center energy 4.5 keV agrees with Gaussian incoherent source profile of full-width-half-maximum (FWHM) < 8 microm. Analysis indicates this corresponds to an upper limit on the transverse profile of laser-accelerated electrons within the plasma in agreement with three-dimensional, particle-in-cell results (FWHM = 4 microm).

Journal Article↗

Reduction of excess sludge production using mechanical disintegration devices.

The usability of mechanical disintegration techniques for the reduction of excess sludge production in the activated sludge process was investigated. Using three different disintegration devices (ultrasonic homogeniser, stirred media mill, high pressure homogeniser) and different operational parameters of the disintegration, the effect of mechanical disintegration on the excess sludge production and on the effluent quality was studied within a continuously operated, laboratory scale wastewater treatment system with pre-denitrification. Depending on the operational conditions and the disintegration device used, a reduction of excess sludge production of up to 70% was achieved. A combination of mechanical disintegration with a membrane bioreactor process with high sludge age is more energy effective concerning reduction of sludge production than with a conventional activated sludge process at lower sludge ages. Depending on the disintegration parameters, the disintegration has no, or only minor, negative effect on the soluble effluent COD and on the COD-removal capacity of the activated sludge process. Nitrogen-removal was slightly deteriorated by the disintegration, whereas the system used was not optimised for nitrogen removal before disintegration was implemented.

Pressure↗

Pathological cholesterol metabolism fails to modify electrophysiological properties of afflicted neurones in Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is a recessive inherited neurovisceral lipid storage disease characterized by progressive motor impairment and a loss of neurones including those integrated into the motor system. One of the key neuropathological findings is the intracellular accumulation of lysosomes enriched with free cholesterol. This accumulation is due to impaired transport proteins named NPC1 (approx. 95% of the cases) or NPC2 (approx. 5%) responsible for the transport of endocytosed cholesterol from lysomes to plasma membranes. The perturbed lipid-transport in NPC cells leads to an altered lipid composition of the plasma membrane. Available evidence suggests that the lipid matrix influences the electrophysical properties of ion channels in membranes. We therefore evaluated whether electrophysiological properties of NPC neurones differ from healthy neurones. Both, acute brain slices and primary neuronal cell cultures from wildtype and NPC mice, a well-established mouse model for the Niemann-Pick type C disease, were used for a comparison of electrophysiological properties like resting membrane potential, input resistance, action potential amplitudes and synaptic properties of the neurones. In addition we optically recorded the changes of intraneuronal calcium levels elicited by depolarization. Our results show that the characteristics of ion channels in NPC neurones do not differ significantly from wildtype neurones. We therefore conclude that gross alterations of the electrophysiological properties of neurones will probably not initiate or substantially contribute to the development of the motor impairment or other neurological signs of NPC.

Action Potentials↗

Efficacy and safety of subcutaneous immunotherapy with a biologically standardized extract of Ambrosia artemisiifolia pollen: a double-blind, placebo-controlled study.

BACKGROUND: The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America. OBJECTIVE: We sought to study the safety and efficacy of injective immunotherapy in European patients sensitized to Ambrosia artemisiifolia. METHODS: Thirty-two patients (18 M/14 F, mean age 36.78, range 23-60 years) suffering from rhinoconjunctivitis and/or asthma and sensitized to Ambrosia were enrolled and randomized in a double-blind, placebo-controlled (DBPC) study lasting 1 year. A maintenance dose corresponding to 7.2 microg of Amb a 1 was administered at 4-week intervals after the build-up. During the second and the third year, all patients were under active therapy in an open fashion. Symptom and medication scores, skin reactivity to Ambrosia (parallel line biological assay), and pollen counts were assessed throughout the trial. RESULTS: Twenty-three patients completed the trial. No severe adverse event was observed. During the DBPC phase, actively treated patients showed an improvement in asthmatic symptoms (P=0.02) and drug (P=0.0068) scores days with asthmatic symptoms (P=0.003), days with rhinitis symptoms (P=0.05), and days with intake of drugs (P=0.0058), as compared to before therapy. No improvement for any of these parameters was detected in the placebo group. Moreover, the number of days with rhinitis and asthma was significantly higher in the placebo as compared to the active group (P=0.048 and P<0.0001, respectively). Patients who switched from placebo to active therapy improved in rhinoconjunctivitis, asthma, and drug intake. The skin reactivity decreased significantly (12.2-fold, P=0.0001) in the active group whereas a slight increase (1.07-fold, P=0.87) was observed in the placebo group after the DBPC phase. After switching to active therapy, patients previously under placebo showed a significant decrease of this parameter (4.78-fold, P=0.002). CONCLUSION: Injective immunotherapy is safe and clinically effective in European patients sensitized to Ambrosia.

Adult↗

Blockade of HMG-CoA reductase activity causes changes in microtubule-stabilizing protein tau via suppression of geranylgeranylpyrophosphate formation: implications for Alzheimer's disease.

Histopathologically, Alzheimer's disease is characterized by plaques and tangles that develop progressively over time. Experimental data described a statin-induced decrease in beta-amyloid production, a major constituent of the plaques. Others reported data on statin-mediated changes in neuronal survival and cytoskeleton, including the microtubule-associated protein tau, a major constituent of the tangles. However, these latter reports remain contradictory. To clarify and extend our knowledge on the effect of statin on the cytoskeleton, we challenged rat primary neuron cultures by lovastatin and determined the metabolite that is critical for structural integrity and survival of neurons. During the blockade of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the neuritic network was affected and eventually was completely destroyed. This process was not part of the execution phase of apoptosis and was marked by alterations in the microfilament and microtubule system. The distribution and phosphorylation of protein tau changed. Immunoblot analysis and indirect immunofluorescence revealed a transient increase in tau phosphorylation, which ceased during the execution of apoptosis. All of these effects could be linked to the lack of the geranylgeranylpyrophosphate intermediate. Inhibition of the geranylgeranylation of Rho family GTPases (geranylgeranyl-transferase I) evoked similar changes in neurons. These data and our findings that statin treatment reduced the membrane-bound fraction of RhoA-GTPase in neurons suggest that reduced levels of functional small G proteins are responsible for the observed effects. Our data demonstrate that lovastatin concentrations able to suppress not only cholesterol but also geranylgeranylpyrophosphate formation may evoke phosphorylation of tau reminiscent of preclinical early stages of Alzheimer's disease and, when prolonged, apoptosis.

Alzheimer Disease↗

[Potential pro-thrombotic effects of cyclooxygenase-2. inhibitors Two cases pf myocardial infarction].

Type 2 cyclo-oxygenase inhibitors are new anti-inflammatory drugs with better gastrointestinal tolerance than traditional non-steroidal anti-inflammatory drugs. They have no platelet anti-aggregant effects and there is still some discussion as to whether this new therapeutic class has any pro-thrombotic effects. The authors report two cases of myocardial infarction in patients considered to be at low risk treated by type 2 cyclo-oxygenase inhibitors.

Adult↗

Regulation of apolipoprotein E secretion in rat primary hippocampal astrocyte cultures.

Apolipoprotein E isoforms may have differential effects on a number of pathological processes underlying Alzheimer's disease. Recent studies suggest that the amount, rather than the type, of apolipoprotein E may also be an important determinant for Alzheimer's disease. Therefore, understanding the regulated synthesis of apolipoprotein E is important for determining its role in Alzheimer's disease. We show here that in rat primary hippocampal astrocyte cultures, dibutyryl-cAMP increased apolipoprotein E secretion with time in a dose-dependent manner (to 177% at 48 h) and that retinoic acid potentiated this effect (to 298% at 48 h). Dibutyryl-cAMP also gave a rapid, albeit transient, increase of apolipoprotein E mRNA expression (to 200% at 1 h). In contrast, the protein kinase C activator phorbol 12-myristate 13-acetate decreased both apolipoprotein E secretion (to 59% at 48 h) and mRNA expression (to 22% at 1 h). Phorbol 12-myristate 13-acetate also reversed the effects of dibutyryl-cAMP. Apolipoprotein E secretion was also modulated by receptor agonists for the adenylyl cyclase/cAMP pathway. Isoproterenol (50 nM, a beta-adrenoceptor agonist) enhanced, while clonidine (250 nM, an alpha2-adrenoceptor agonist) decreased, secreted apolipoprotein E. We also analysed the effects of agonists for the phospholipase C/protein kinase C pathway. Arterenol (1 microM, an alpha1-adrenoceptor agonist) and serotonin (2.5 microM) enhanced, whereas carbachol (10 microM, an acetylcholine muscarinic receptor agonist) decreased secreted apolipoprotein E. The effects of these non-selective receptor agonists were modest, probably due to effects on different signalling pathways. Arterenol also potentiated the isoproterenol-mediated increase. We also show that phorbol 12-myristate 13-acetate and dibutyryl-cAMP have opposite effects on nerve growth factor, as compared to apolipoprotein E, secretion, suggesting that the results obtained were unlikely to be due to a general effect on protein synthesis. We conclude that astrocyte apolipoprotein E production can be regulated by factors that affect cAMP intracellular concentration or activate protein kinase C. Alterations in these signalling pathways in Alzheimer's disease brain may have consequences for apolipoprotein E secretion in this disorder.

Alzheimer Disease↗

[Polyradiculopathy caused by cytomegalovirus in AIDS patients: successful treatment with highly active antiretroviral therapy (HAART)].

We report two male patients with AIDS, aged 23 and 30 years old respectively. One was admitted due to a progressive weakness of the left leg and urinary and fecal incontinence. The other was admitted due to a progressive paraparesia without incontinence, but with a severe lumbar pain. In both patients polymerase chain reactions for cytomegalovirus in cerebrospinal fluid were positive. Treatment with ganciclovir, for 21 and 14 days respectively and highly active antiretroviral therapy was started. Both patients experienced recovery of their neurological deficits after 98 and 88 days of therapy, respectively.

AIDS-Related Opportunistic Infections↗

Effects of ephedrine on the onset time of neuromuscular block and intubating conditions after cisatracurium: preliminary results.

We studied the effects of intravenous ephedrine on the onset time and the intubating conditions 2 min after a bolus dose of cisatracurium (0.15 mg kg-1). Thirty patients anaesthetized with sufentanil and propofol were randomly divided in 2 groups to receive either ephedrine (70 micrograms.kg-1) or saline, 5 s before propofol. Cisatracurium was administered after loss of consciousness. Neuromuscular block was assessed at the adductor pollicis using accelography. Tracheal intubation was performed 2 min after cisatracurium injection and rated as excellent, good, poor or bad. At intubation, neuromuscular block (% height of control T1) was greater in patients receiving ephedrine (36.1 +/- 25.8% vs 57.9 +/- 25.1%) (mean +/- SD). The frequency of excellent intubating conditions was higher after ephedrine (86.6%) than after saline (40.0%). The onset time of cisatracurium was shorter after ephedrine (167 +/- 64.8 s vs 234.9 +/- 63.1 s). Thus, a low dose of ephedrine given before induction of anaesthesia improves the intubating conditions 2 min after 0.15 mg kg-1 cisatracurium and this effect likely relates to a quicker onset of neuromuscular block.

Adult↗

Culture of autopsy-derived fibroblasts as a tool to study systemic alterations in human neurodegenerative disorders such as Alzheimer's disease--methodological investigations.

The present study was undertaken in order to analyse the possibility of culturing post mortem derived human fibroblasts. The combination of post mortem fibroblasts with the autopsy proven and histopathologically staged brain will allow the correlative investigation of dynamic biochemical processes which are systemically underlying or accompanying a neurological and/or psychiatric disorder. These studies are limited in autopsy brain or are uncertain when the neuropathological status is lacking, i.e. when fibroblasts were obtained from living patients. Our examinations of human autopsy fibroblast and those under experimentally controlled post mortem conditions with rats clearly demonstrate that autopsy-derived fibroblasts can be reliably cultured. The cells grown displayed typical morphological and staining characteristics as well as pharmacological responsiveness. Even cells obtained from a 99 years old individual or an individual with a post mortem delay of 48 hours grew in our culture system.

Aged↗

The effects of beta/A4-amyloid and its fragments on calcium homeostasis, glial fibrillary acidic protein and S100beta staining, morphology and survival of cultured hippocampal astrocytes.

Aggregated beta/A4-amyloid is known to increase intraneuronal calcium by various mechanisms and to lead eventually to the death of the cultured neuron. This study deals with the role of beta/A4-amyloid and several of its fragments in calcium homeostasis, glial fibrillary acid protein and S100beta staining, morphology and survival of cultured rat hippocampal astrocytes as determined by Fura imaging, indirect immunofluorescence and life/death assays. In contrast to cultured neurons, none of the 12 different beta/A4 fragments tested caused an increase in intra-astrocytic free calcium. However, among the compounds evaluated, the fragments 10-20mer, 25-35mer and the full-length peptides (1-40, 1-42 and 1-43mer), at 5 and 10 microM, decreased free intra-astrocytic calcium statistically significantly after the cells had been incubated for 48 and 72 h. This occurred both for astrocytes treated with vehicle alone or the reversed sequence of the 1-40mer, i.e. the 40-1mer. However, survival was not altered under the conditions examined, even when there was a change in free intracellular calcium. Concomitant with the decrease in intracellular free calcium, the shape of the astrocytes became more spider-like, normally an indication of activated astrocytes, and markedly more intense anti-S100beta and anti-glial fibrillary acidic protein staining was seen. The functional relevance of altered calcium homeostasis for apolipoprotein E secretion, potentially relevant for neuronal plasticity in general and in Alzheimer's disease, is discussed.

Amyloid beta-Protein Precursor↗

The detection of intrathecal synthesis of anti-herpes simplex IgG antibodies: comparison between an antigen-mediated immunoblotting technique and antibody index calculations. European Union Concerted Action on Virus Meningitis and Encephalitis.

The detection of intrathecal antibody synthesis was compared by the calculation of antibody indices (AI) derived from ELISA techniques with the detection of virus-specific oligoclonal IgGs by an antigen-mediated capillary blot technique. Twenty-seven paired serum and cerebrospinal fluid (CSF) samples were examined from 15 immunocompetent patients with herpes simplex virus encephalitis (HSE) diagnosed by PCR on early CSF samples. These techniques were also applied to paired samples from 20 multiple sclerosis (MS) patients, 10 patients with other inflammatory neurological diseases and 10 patients with non inflammatory neurological disorders. There was a good correlation between the results obtained by AI and those obtained by immunoblotting, especially in HSE (2 discordant results out of 27). Discrepancies were more frequent (25%) in MS patients where a "polyspecific" reaction characterized by low affinity antibodies is known to occur. Some of the discrepancies could, in part, be due to serological cross-reaction with varicella zoster virus.

Adolescent↗

Haematoma evacuation does not improve outcome in spontaneous supratentorial intracerebral haemorrhage: a case-control study.

Surgical intervention in supratentorial intracerebral haemorrhage (ICH) is still controversial. We assessed the value of haematoma evacuation with a case-control study. 145 consecutive patients with supratentorial spontaneous ICH without tumour or vascular abnormalities were analysed. Haematoma evacuation was performed in 24 patients. Age, sex, Glasgow Coma Scale (GCS), level of consciousness, pupillary reaction on admission, localisation, aetiology and volume of the haematoma, presence of ventricular blood, and Glasgow Outcome Scale (GOS) on discharge were analysed. From statistical analysis 40 patients > 80 years and with haematoma volume < 10 ml, who were always treated conservatively, were excluded. Prognostic factors retained from a multiple regression model with the dichotomised GOS scale (GOS 1-3, 4 + 5) as response variable were GCS, haematoma volume and location. The only difference between all medically treated and "operated" patients was haematoma volume, which was larger in the "operated" patients. All 24 evacuated cases could be matched to a medically treated control regarding age, haematoma volume and location, GCS, and pupillary reaction. Significant differences between the two groups could not be detected. Outcome was not different between the two groups. After separating the sample into patients with and without ventricular haemorrhage, there was no different outcome between the two groups either. We conclude that haematoma evacuation did not improve outcome in supratentorial spontaneous ICH. Since haematomas were evacuated mainly in clinically deteriorating patients, our data suggest that the only effect of haematoma evacuation is to stop progressive deterioration rather than to improve overall clinical outcome.

Adult↗

Craniectomy: an aggressive treatment approach in severe encephalitis.

BACKGROUND AND OBJECTIVE: Focal encephalitis may be associated with brain edema, which is often fatal. The control of intracranial pressure (ICP) is therefore crucial for further therapeutic strategies in space-occupying edema following encephalitis. However, aggressive treatment strategies such as hemicraniectomy have not been described in a larger series of patients. PATIENTS AND METHODS: We describe the clinical course and outcome in six patients who developed severe brain edema associated with acute encephalitis. All received maximum medical treatment for elevated ICP, but with signs of brainstem compression emerging, hemicraniectomy was performed to control ICP. RESULTS: All patients had a very severe encephalitic syndrome and were treated over the course of weeks in the neurocritical care unit (NCCU). However, all patients recovered almost completely and showed only mild or no neurologic deficit when reexamined after 4 months to 3 years. CONCLUSIONS: Hemicraniectomy should be considered in patients with severe brain edema following encephalitis as a potentially lifesaving therapeutic measure. Moreover, the initial neurologic deficit seems to have no impact on the long-term clinical outcome.

Adult↗

[Outcome of profile-improving operations in craniofacial abnormalities].

In 52 children with craniosynostosis, we studied the effect of fronto-orbital advancement onto the forehead profile and the growth tendency of the forehead and midface. As a reference, the following kephalometric data were used: SN line. N-Spna line, SNA angle, N-tf line (as an indicator of the forehead profile) and the tf-TF line (as an indicator of the forehead size). The operation was carried out at an mean age of 10.5 months. Follow-up with X-ray control covered a period of 37.2 months on average. In patients with brachycephalus the SNA line was reduced and the post-operative growth tendency was the most unfavorable. Also the forehead profile (N-tf-line) did not become normal after the operation in patients with brachycephalus. Besides this, the increase in the forehead size indicated a new growth-tendency disorder. In all children with brachycephalus as well as in most children with oxycephalic growth tendency, sagittal midface growth was inhibited (NSA angle) while vertical midface growth was normal (N-Spna line). The success of fronto-orbital advancement was dependent on the kind of growth disorder, the location, and the age when the operation was carried out. Only early operative treatment could interrupt the pathological growth tendency even in cases with a major development disorder.

Cephalometry↗