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Biomedical subjects

G Mayer

Publications and source records attributed to G Mayer.

At least 19 recordsLinked to original sources
PubMed2006

Gene expression profiles of human proximal tubular epithelial cells in proteinuric nephropathies.

In kidney disease renal proximal tubular epithelial cells (RPTEC) actively contribute to the progression of tubulointerstitial fibrosis by mediating both an inflammatory response and via epithelial-to-mesenchymal transition. Using laser capture microdissection we specifically isolated RPTEC from cryosections of the healthy parts of kidneys removed owing to renal cell carcinoma and from kidney biopsies from patients with proteinuric nephropathies. RNA was extracted and hybridized to complementary DNA microarrays after linear RNA amplification. Statistical analysis identified 168 unique genes with known gene ontology association, which separated patients from controls. Besides distinct alterations in signal-transduction pathways (e.g. Wnt signalling), functional annotation revealed a significant upregulation of genes involved in cell proliferation and cell cycle control (like insulin-like growth factor 1 or cell division cycle 34), cell differentiation (e.g. bone morphogenetic protein 7), immune response, intracellular transport and metabolism in RPTEC from patients. On the contrary we found differential expression of a number of genes responsible for cell adhesion (like BH-protocadherin) with a marked downregulation of most of these transcripts. In summary, our results obtained from RPTEC revealed a differential regulation of genes, which are likely to be involved in either pro-fibrotic or tubulo-protective mechanisms in proteinuric patients at an early stage of kidney disease.

Aged↗
PubMed2006

Effects of loading rate on the mechanical behavior of a natural rigid composite.

The effects of loading rate variations on the stress-strain behavior, failure mechanisms, fracture modes, and energy-dissipating capability of the spicules of the sponge Euplectella aspergillum have been investigated. Comparisons were made with similar measurements on a silicate glass. It was concluded that the very thin (5-10nm) organic layers that are interspersed with thicker layers of hydrated silica in the concentric ring structure of the spicules strongly influence all aspects of the mechanical behavior.

Animals↗
PubMed2006

[Sleep in neurodegenerative disorders].

Neurodegenerative disorders are a group of heterogeneous, progressive disorders of varying etiology that affect one or more systems. They occur predominantly at older age, during which the structure and amount of sleep undergo changes. Neurodegenerative processes cause structural changes of the sleep/wake generators in the brainstem which result in disorders such as daytime sleepiness, insomnia, sleep-related movement and breathing disturbances, and disorders of the circadian rhythms. Some sleep disorders manifest years before the onset of neurodegenerative disorders and may serve as predictors. Polysomnography shows sleep fragmentation, tonic or phasic movements of the extremities, alteration of respiratory muscles, reduced slow wave sleep, REM sleep absence or without muscle atonia, increased arousal or wake activity, epileptiform EEG activity, and changes in sleep-related breathing. Very frequently, REM sleep behaviour disorder is associated with neurodegenerative disorders. In this overview we present symptoms, pathophysiology, and polysomnographic findings of sleep disorders in prevalent neurodegenerative disorders.

Brain Stem↗
PubMed2006

Expression and localization of MT1-MMP and furin in the glomerular wall of short- and long-term diabetic rats.

Diabetic glomerulopathy has been linked to shifts in balance between the synthetic and degradative pathways of the glomerular basement membrane (GBM), a key player in the permselectivity properties of the glomerular wall. The goal of this study was to trace the expression and localization of membrane type-1 metalloprotease (MT1-MMP) and its activating enzyme furin, key proteins involved in basement membrane turnover, in short- and long-term diabetic rat renal tissues. Quantitative immunogold was carried out for MT1-MMP and furin and their expression was evaluated in renal tissues of young and old, control and diabetic rats. To corroborate immunocytochemical findings, Western blots were performed on glomerular lysates. Electron microscopy revealed that the overall expression of MT1-MMP and furin is reduced in plasma membranes of all glomerular cell types of old normoglycemic animals, a phenomenon that is exacerbated in long-term diabetic animals. This observation supports the prevailing theory that diabetes fosters acceleration in the aging process. Interestingly, while biochemical results confirmed a decrease in MT1-MMP expression, an increase in furin was observed. Immunocytochemical studies resolved this discrepancy by tracing the increased furin expression in endoplasmic reticulum and Golgi membranes of podocytes, indicating that furin is retained in the secretory pathway in a diabetic environment. Disturbances at the molecular level of the otherwise tightly regulated MT1-MMP/furin interactions found at the cell surface must account for a lack in extracellular matrix remodeling, increased deposition of GBM material, and loss of glomerular filtration integrity.

Animals↗
PubMed2006

Secondary sclerosing cholangitis after long-term treatment in an intensive care unit: clinical presentation, endoscopic findings, treatment, and follow-up.

BACKGROUND AND STUDY AIMS: We present ten patients who developed secondary sclerosing cholangitis following long-term treatment in an intensive care unit (ICU) between 1999 and 2004. PATIENTS AND METHODS: Ten consecutive patients who had no evidence suggestive of pre-existing hepatobiliary disease were admitted to an ICU because of trauma (n = 5), intracerebral hemorrhage (n = 3), or nonabdominal postsurgical complications (n = 2). All the patients had required treatment with long-term ventilation, catecholamines, total parenteral nutrition, and several antimicrobial agents. RESULTS: Cholestasis was first noted within 11 days after the initial insult. Endoscopic retrograde cholangiopancreatography (ERCP), performed after a median follow-up of 69 days, revealed multifocal stricturing and beading of the intrahepatic bile ducts, and attenuation of the peripheral branches. In all the patients, the bile ducts were partially filled by black-pigmented thrombotic material. All the patients underwent endotherapy, which comprised sphincterotomy and removal of the occluding material, in an attempt to improve biliary drainage; the treatment had to be repeated in seven of the ten patients. After a median follow-up period of 21 months, despite transient clinical improvement following endotherapy, complete recovery has not been achieved in any of the patients and so far one patient has had to undergo orthotopic liver transplantation as a result of end-stage liver disease. CONCLUSIONS: The development of secondary sclerosing cholangitis in patients who have received long-term treatment in an ICU is a rare event of unknown pathophysiology, but patients demonstrate characteristic findings on ERCP. It is not known whether endotherapy can delay the progress of the condition in the long term.

Adult↗
PubMed2006

Protein biomarkers associated with acute renal failure and chronic kidney disease.

Acute renal failure (ARF) as well as chronic kidney disease (CKD) are currently categorized according to serum creatinine concentrations. Serum creatinine, however, has shortcomings because of its low predictive values. The need for novel markers for the early diagnosis and prognosis of renal diseases is imminent, particularly for markers reflecting intrinsic organ injury in stages when glomerular filtration is not impaired. This review summarizes protein markers discussed in the context of ARF as well as CKD, and provides an overview on currently available discovery results following 'omics' techniques. The identified set of candidate marker proteins is discussed in their cellular and functional context. The systematic review of proteomics and genomics studies revealed 56 genes to be associated with acute or chronic kidney disease. Context analysis, i.e. correlation of biological processes and molecular functions of reported kidney markers, revealed that 15 genes on the candidate list were assigned to the most significant ontology groups: immunity and defence. Other significantly enriched groups were cell communication (14 genes), signal transduction (22 genes) and apoptosis (seven genes). Among 24 candidate protein markers, nine proteins were also identified by gene expression studies. Next generation candidate marker proteins with improved diagnostic and prognostic values for kidney diseases will be derived from whole genome scans and protemics approaches. Prospective validation still remains elusive for all proposed candidates.

Acute Kidney Injury↗
PubMed2006

EFNS guidelines on management of narcolepsy.

Management of narcolepsy with or without cataplexy relies on several classes of drugs, namely stimulants for excessive daytime sleepiness and irresistible episodes of sleep, antidepressants for cataplexy and hypnosedative drugs for disturbed nocturnal sleep. In addition, behavioral measures can be of notable value. Guidelines on the management of narcolepsy have already been published. However contemporary guidelines are necessary given the growing use of modafinil to treat excessive daytime sleepiness in Europe within the last 5-10 years, and the decreasing need for amphetamines and amphetamine-like stimulants; the extensive use of new antidepressants in the treatment of cataplexy, apart from consistent randomized placebo-controlled clinical trials; and the present re-emergence of gamma-hydroxybutyrate under the name sodium oxybate, as a treatment of all major symptoms of narcolepsy. A task force composed of the leading specialists of narcolepsy in Europe has been appointed. This task force conducted an extensive review of pharmacological and behavioral trials available in the literature. All trials were analyzed according to their class evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive daytime sleepiness and irresistible episodes of sleep in association with behavioral measures. However, based on several large randomized controlled trials showing the activity of sodium oxybate, not only on cataplexy but also on excessive daytime sleepiness and irresistible episodes of sleep, there is a growing practice in the USA to use it for the later indications. Given the availability of modafinil and methylphenidate, and the forseen registration of sodium oxybate for narcolepsy (including excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep) in Europe, the place of other compounds will become fairly limited. Since its recent registration cataplexy sodium oxybate has now become the first-line treatment of cataplexy. Second-line treatments are antidepressants, either tricyclics or newer antidepressants, the later being increasingly used these past years despite few or no randomized placebo-controlled clinical trials. As for disturbed nocturnal sleep the best option is still hypnotics until sodium oxybate is registered for narcolepsy. The treatments used for narcolepsy, either pharmacological or behavioral, are diverse. However the quality of the published clinical evidences supporting them varies widely and studies comparing the efficacy of different substances are lacking. Several treatments are used on an empirical basis, specially antidepressants for cataplexy, due to the fact that these medications are already used widely in depressed patients, leaving little motivation from the manufacturers to investigate efficacy in relatively rare indications. Others, in particular the more recently developed substances, such as modafinil or sodium oxybate, are evaluated in large randomized placebo-controlled trials. Our objective was to reinforce the use of those drugs evaluated in randomized placebo-controlled trials and to reach a consensus, as much as possible, on the use of other available medications.

Advisory Committees↗
PubMed2005

Physico-chemical and biological evaluation of excimer laser irradiated polyethylene terephthalate (pet) surfaces.

The aim of this work was to investigate the consequences of excimer laser irradiation on the physico-chemical and biological properties of polyethylene terephthalate (PET) films, currently used for medical devices. Three PET films from different origins were studied in the present work, chosen with respect to their chemical and physical properties, which are of high importance for ulterior medical application as vascular prostheses. Multiple assays were carried out to characterize the physical and chemical effects of the laser irradiation: surface morphology tests (light microscopy, Dektak profilometer and confocal laser scanning microscopy) showed the strong transformation of the surface with the laser treatment. Contact angle measurements revealed a significant increase of the surface energy for each PET depending on the applied fluency. Finally XPS characterization of the surface demonstrated the appearance of new chemical species favorable for cell attachment. This aspect had to be strongly considered regarding to the multiple biological effects of laser irradiated surfaces on living cells. Different cell culture experiments were carried out with L132 human epithelial cells after 6-days culture: proliferation and vitality rate, cell adhesion and cell morphology. Results clearly revealed that laser treatment improved cell proliferation (up to 140% with respect to controls), vitality (10% higher than controls), morphology and adhesion kinetics (more than 16% of control). A significant correlation (R2=0.906) was also established on one PET between the fluencies of laser treatment and the cellular response. These results emphasized high importance of the choice of the PET material for a medical application: only one of the three considered PET films showed really improved cellular response.

Biocompatible Materials↗
PubMed2005

Evaluation of oxidative stress measurements in obstructive sleep apnea syndrome.

Assessment of reactive oxygen species (ROS) is highly important in neurodegenerative disorders and neuroleptic treatment. However, conflicting results have been reported, which may arise from methodological difficulties. Obstructive sleep apnea (OSA) syndrome with episodic hypoxia-reoxygenation is proposed as a human model for the investigation of ROS measurements. Despite a broad analytical approach comprising lipid peroxidation and amino acid oxidation products, oxidative DNA damage, and activity of the antioxidant defense, only plasma malondialdehyde (MDA) and urinary o,o'-dityrosine seemed to be appropriate, robust biomarkers of oxidative stress, which are also simple enough for routine clinical use. MDA concentrations correlated with a duration of nocturnal desaturation below 85% (r = 0.77, p<0.0005), and o,o'-dityrosine levels decreased after therapy (p<0.05) as a function of baseline concentrations (r = -0.61, p<0.05). Gender effects in ROS generation also have to be considered. At present, we recommend the application of several oxidative stress measurements at different time points, preferably involving plasma MDA and urinary o,o'-dityrosine.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

[The neurophysiology of cataplexy].

Cataplexy and excessive daytime sleepiness are the leading symptoms of narcolepsy. Electrophysiological studies in humans do not show a clear association between cataplexy and rapid eye movement (REM) sleep. Even a decrement of the H reflex is not specific for cataplexy and may be caused by unspecific triggers such as coughing. Cholinomimetics, which may induce status cataplecticus, do not influence REM sleep, thus evidencing a REM-independent mechanism. Recent studies demonstrate a lack of the neuropeptide hypocretin in the CSF of narcoleptics. Hypocretin controls wakefulness and the motor and autonomous systems. In hypocretin-1 and -2 knockout mice, sudden stops of motor activity could be observed in emotional situations that were accompanied by sudden shifts from wakefulness to REM sleep and could be terminated by application of anticataplectic medication. The lack of hypocretin not only causes a noradrenergic-cholinergic imbalance in the midbrain but also influences motoneurons directly by juxtacellular hypocretin-containing membranes. Intravenous application of hypocretin in a dog with hypocretin deficiency in the CSF caused a dose-dependent decrease of cataplexies. An understanding of the neuronal mechanisms responsible for cataplexies is essential for the development of new anticataplectic medications.

Animals↗
PubMed2004

Combination of 'idiopathic' REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT.

REM sleep behaviour disorder (RBD) and olfactory dysfunction are common and very early features of alpha-synucleinopathies, in particular Parkinson's disease. To investigate the hypothesis that these two clinical features in combination are an indicator of evolving alpha-synucleinopathy, olfactory function was assessed in RBD. We studied 30 patients (18 male, 12 female; mean age 48 +/- 14 years, range 19-78 years) with clinical (idiopathic, n = 6; symptomatic, n = 13, mostly associated with narcolepsy) or subclinical (n = 11, associated with narcolepsy) RBD according to standard criteria and 30 age- and gender-matched healthy control subjects using standardized 'Sniffin' Sticks'. RBD patients had a significantly higher olfactory threshold (P = 0.0001), lower discrimination score (P = 0.003), and lower identification score (P = 0.001). Compared with normative data, 97% of the RBD patients had a pathologically increased olfactory threshold, 63% an impaired odour discrimination score, and 63% a decreased identification score. On neurological examination, signs of parkinsonism were newly found in five patients with clinical RBD (not associated with narcolepsy), who usually had a long history of 'idiopathic' RBD. Four of the five patients fulfilled the UK Brain Bank criteria for the clinical diagnosis of Parkinson's disease. The underlying nigrostriatal degeneration of clinical Parkinson's disease was confirmed by I-123-FP-CIT SPECT in one patient and early nigrostriatal degeneration was identified by SPECT in a further two patients with 'idiopathic' clinical RBD out of 11 RBD patients who agreed to undergo SPECT studies. Our study shows that RBD patients have a profound impairment of olfactory function. Five patients with clinical RBD not associated with narcolepsy had clinical or imaging signs of nigrostriatal degeneration. This new clinical finding correlates with the neuropathological staging of Parkinson's disease (stages 1-3) as proposed by Braak. In stage 1, the anterior olfactory nucleus or the olfactory bulb is affected (along with the dorsal motor nucleus of the glossopharyngeal and vagal nerves). In stage 2, additional lesions consistently remain confined to the medulla oblongata and pontine tegmentum, which are critical areas for RBD. Midbrain lesions are found only in stage 3, in particular degeneration of dopaminergic neurons in the substantia nigra pars compacta. Thus, 'idiopathic' RBD patients with olfactory impairment might present with stage 2 preclinical alpha-synucleinopathy. Since narcoleptic patients are not known to have an increased risk of developing parkinsonism, the pathophysiology and clinical relevance of hyposmia in RBD/narcolepsy patients requires further research.

Adult↗
PubMed2004

PCR-detected hepatitis C virus RNA associated with human zona-intact oocytes collected from infected women for ART.

BACKGROUND: The aim of this study was to investigate the susceptibility of human oocytes from hepatitis C virus (HCV) RNA-positive women to HCV contamination during assisted reproductive technology (ART). METHODS: A reverse transcriptase-PCR assay was used to test for the presence of HCV RNA associated with 24 unfertilized oocytes 48 h after follicular fluid aspiration in 10 IVF attempts (seven conventional IVF and three ICSI). Negative and positive controls (10 unfertilized oocytes from HCV-negative women and 20 unfertilized oocytes artificially contaminated with HCV RNA-positive plasma; HCV RNA was also quantified in plasma and follicular fluid) were included. RESULTS: HCV RNA was associated with 17/24 (70.8%) oocytes (6/7 after ICSI and 11/17 after conventional IVF) and was found in 19/20 (95%) follicular fluid samples. A weak correlation was found between plasma and follicular fluid HCV RNA loads (r = 0.73, P < 0.001). CONCLUSIONS: HCV associated with unfertilized oocytes surrounded by their intact zona pellucida from anti-HCV antibody-positive and viraemic women undergoing ART raises questions concerning the safe management of medically assisted procreation for these women and good practice of oocyte/embryo cryopreservation and donation.

Adult↗
PubMed2004

[Sleep disorders and sleep-related breathing disorders].

Normal sleep consists of 4-5 sleep cycles including light-, deep- and rapid eye-movement sleep. Restoration of physical and psychological function are the main effects of sleep. In most cases, disturbances of normal sleep become clinically evident as problems of initiating and maintaining sleep and/or as increased daytime sleepiness. Approximately 10% of adults suffer from pronounced insomnia, a similar percentage from markedly increased daytime sleepiness. Sleep disorders cause high socio-economic costs due to increased accident risk, cardiovascular sequelae and sick leave. Most of the 88 distinct diagnoses summarized in the international classification of sleep disorders can be differentiated and managed according to patients history. In patients with severe daytime sleepiness - sleep disordered breathing being the most frequent cause - the diagnostic evaluation and treatment in the sleep laboratory is required. Effective therapeutic strategies are available for many sleep disorders. According to the underlying disorder, treatment includes a variety of measures like life style changes, differentiated medical treatment and the use of nasally applied positive pressure in patients suffering from sleep disordered breathing.

Activities of Daily Living↗
PubMed2004

CPAP-therapy effectively lowers serum homocysteine in obstructive sleep apnea syndrome.

Assessment of serum total homocysteine (tHcy) in patients with obstructive sleep apnea (OSA) syndrome is highly relevant since both are strongly associated with stroke and cognitive dysfunction. Seven of 16 untreated OSA patients showed tHcy levels exceeding 11.7 micromol/l. The circadian pattern of serum tHcy in untreated and treated patients (p < 0.001) implied a diagnostic impact of blood sampling time. Treatment with continuous positive airway pressure (CPAP) effectively lowered tHcy levels in patients by about 30% (p < 0.005) and thus probably the (hyper)homocysteinemia-related cognitive dysfunction and the risk for cardio-/cerebrovascular diseases.

Chromatography, High Pressure Liquid↗
PubMed2004

Cerebral vasculitis in a patient with hereditary complete C4 deficiency and systemic lupus erythematosus.

We describe the case of a female patient with hereditary complete C4 deficiency and systemic lupus erythematosus. She had suffered from lupus nephritis in early childhood. At the age of 23 years she developed severe lupus with skin disease and life-threatening cerebral vasculitis. Her cerebral disease was unresponsive to high-dose steroids, intravenous immunoglobulin, fresh frozen plasma and plasma exchange. Improvement was achieved with immunoadsorption in combination with mycophenolate mofetil. The patient made a complete recovery and is maintained in complete remission on mycophenolate and low-dose steroids.

Adult↗