Evidence of cortical learning in vegetative state.
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Acoustic Stimulation↗
Biomedical subjects
S Lang
Publications and source records attributed to S Lang.
A tissue engineering approach to meniscus regeneration in a sheep model.
OBJECTIVE: Regeneration of the meniscal tissue occurs to a limited extent, and the loss of meniscal tissue leads to osteoarthritis. A new biomaterial consisting of hyaluronic acid and polycaprolactone was used as a meniscus substitute in sheep to evaluate the properties of the implant material with regard to size, biomechanical stability, tissue ingrowth, and integration. METHODS: Eight sheep (right stifle joints) were treated with three total and three partial meniscus replacements while two meniscectomies served as empty controls. The animals were euthanized after 6 weeks. The specimens were assessed by gross inspection and histology, and compared with the nonoperated left joints. RESULTS: The surgical technique was found to be feasible. The implants remained in position, did not tear, and showed excellent tissue ingrowth to the capsule. Tissue integration was also observed between the original meniscus and the implant. However, graft compression and extrusion occurred. The histological investigation revealed tissue formation, cellular infiltration and vascularization. Cartilage degeneration was more severe in the operated joints. CONCLUSION: The present study shows promising results concerning the qualities of this biomaterial with regard to implantation technique, stability and tissue ingrowth.
Adjuvants, Immunologic↗
Bioactive hydroxyphenylpyrrole-dicarboxylic acids from a new marine Halomonas sp.: Production and structure elucidation.
The new marine Halomonas sp. strain GWS-BW-H8hM (DSM 17996) was found to produce 3-(4'-hydroxyphenyl)-4-phenylpyrrole-2,5-dicarboxylic acid (HPPD-1) and 3,4-bis(4'-hydroxy- phenyl)pyrrole-2,5-dicarboxylic acid (HPPD-2). In initial cultivations using marine broth, only low contents of these compounds have been isolated. Improving the conditions and growing the strain on artificial seawater supplemented with tryptone 10 g l(-1), yeast extract 5 g l(-1), L-tyrosine 0.6 g l(-1), glycine 1 g l(-1), and glucose 6 g l(-1), the growth-associated HPPD-1 and HPPD-2 production of a 40-l batch cultivation reached the amounts of 47 mg l(-1) and 116 mg l(-1), respectively, after 65 h. Both compounds showed potent anti-tumor-promoting activities.
Anticarcinogenic Agents↗
The serological diagnosis of staphylococcal infective endocarditis.
OBJECTIVES: Establishing the diagnosis of infective endocarditis (IE) can be difficult when blood cultures remain sterile or echocardiography is inconclusive. Staphylococcus aureus is a common aetiological microorganism in IE and is associated with severe valvular destruction and increased mortality. Early diagnosis using culture and antibiotic independent tests would be preferable to allow prompt antibiotic administration. We have developed and evaluated 2 serological assays for the rapid identification of a staphylococcal aetiology in infective endocarditis. The assays measure IgG against whole cells of S. aureus and IgG against lipid S, a novel extracellular antigen released by Gram-positive microorganisms. METHODS: Serum was collected from 130 patients with IE and 94 control patients. IgG against whole cells of S. aureus and against lipid S was measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Anti-lipid S IgG titres were higher in IE caused by Gram-positive microorganisms than in controls (p<0.0001) and higher in staphylococcal IE than in both controls and IE caused by other microorganisms (p=0.0003). Anti-whole cell staphylococcal IgG was significantly higher in serum from patients with staphylococcal IE than in IE caused by other microorganisms and control samples (p<0.0001). CONCLUSION: High anti-whole cell IgG titres are predictive of a staphylococcal aetiology in IE. Elevated serum anti-lipid S IgG titres are predictive of Gram-positive infection compared to controls, very high titres being associated with staphylococcal IE.
Antibodies, Bacterial↗
Prognostic value of haemoglobin levels during concurrent radio-chemotherapy in the treatment of oesophageal cancer.
AIMS: To evaluate the prognostic value of haemoglobin levels during radio-chemotherapy for overall survival, metastases-free survival (MFS) and locoregional control in patients with locally advanced oesophageal cancer. MATERIALS AND METHODS: Age, gender, performance status, tumour location, tumour length, histology, histologic grading, T-stage, N-stage, UICC-stage and weekly haemoglobin levels during concurrent radio-chemotherapy were retrospectively investigated and related to outcome in 108 patients, who received radio-chemotherapy for stage II/III oesophageal cancer. Radio-chemotherapy consisted of 59.4-60 Gy irradiation, two to four courses of cisplatin (75 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 on days 1-5). Haemoglobin levels during radio-chemotherapy were compared among the following three groups: patients with over 60% of haemoglobin levels less than 12 g/dl; patients with over 60% of haemoglobin levels at 12-14 g/dl; and patients with over 60% of haemoglobin levels greater than 14 g/dl. RESULTS: On univariate analysis, haemoglobin levels of 12-14 g/dl and greater than 14 g/dl during concurrent radio-chemotherapy provided better outcomes than haemoglobin levels less than 12 g/dl. The 2-year overall survival rates were 34%, 35% and 16%, respectively (P = 0.002). The 2-year MFS survival rates were 23%, 46% and 21%, respectively (P = 0.06). The 2-year locoregional control rates were 44%, 58% and 19%, respectively (P < 0.001). ECOG performance status (1 better than 2-3) was significantly associated with overall survival (P = 0.013), tumour length (<7 cm better than > or = 7 cm) with overall survival (P = 0.002) and MFS (P = 0.002), N-stage (N0 better than N1) with overall survival (P = 0.004) and MFS (P < 0.001), and UICC-stage (stage II better than III) with overall survival (P = 0.025) and MFS (P = 0.010). On multivariate analysis, haemoglobin levels during radio-chemotherapy maintained significance for overall survival (P = 0.002) and locoregional control (P < 0.001), tumour length for overall survival (P = 0.002) and MFS (P = 0.008), and N-stage for MFS (P = 0.003). CONCLUSIONS: Haemoglobin during radiotherapy and concurrent radio-chemotherapy is an independent prognostic factor in oesophageal cancer treatment. To improve outcome, it seems important to maintain the haemoglobin at 12-14 g/dl.
Antineoplastic Combined Chemotherapy Protocols↗
Azide rearrangements in electron-deficient systems.
The azide group has a diverse and extensive role in organic chemistry, reflected in the power of azide anion as a strong nucleophile, the role of organic azides as excellent substrates for cycloaddition reactions, the uses of azides as precursors of amines and nitrenes, and azide rearrangements known as the Curtius and Schmidt reactions. In recent years the scope of the Schmidt reaction has begun to be explored in depth, so that it now represents an important reaction in synthetic chemistry. This tutorial review analyses and summarises key recent developments in the field of Schmidt reactions.
Alcohols↗
Fed-batch bioreactor production of mannosylerythritol lipids secreted by Pseudozyma aphidis.
Two strains of Pseudozyma aphidis, DSM 70725 and DSM 14930, were used for the bioreactor production of mannosylerythritol lipids (MELs). Foam formation interfered substantially with the cultivation process. Soybean oil was simultaneously employed as both carbon source and anti-foam agent. Primary MEL formation occurred after nitrate limitation. After a first short time-period of nitrate limitation and further nitrate addition, MELs were secreted in spite of nitrate excess. The sedimentation of MEL-enriched beads indicated enhanced product formation. Maximum yield, productivity and yield coefficient of 165 g l(-1), 13.9 g l(-1) day(-1) and 0.92 g g(-1) were achieved using strain DSM 14930 with additional substrate-feeding (glucose, sodium nitrate, yeast extract) and a foam-controlled soybean oil supply.
Biomass↗
Comparison of radio frequency energy absorption in ear and eye region of children and adults at 900, 1800 and 2450 MHz.
The increasing use of mobile communication devices, especially mobile phones by children, has triggered discussions on whether there is a larger radio frequency (RF) energy absorption in the heads of children compared to that of adults. The objective of this study was to clarify possible differences in RF energy absorption in the head region of children and adults using computational techniques. Using the finite-difference time-domain (FDTD) computational method, a set of specific absorption rate (SAR) calculations were performed for anatomically correct adult and child head models. A half-wave dipole was used as an exposure source at 900, 1800 and 2450 MHz frequencies. The ear and eye regions were studied representing realistic exposure scenarios to current and upcoming mobile wireless communication devices. The differences in absorption were compared with the maximum energy absorption of the head model. Four magnetic resonance imaging (MRI) based head models, one female, one adult, two child head models, aged 3 and 7 years, were used. The head models greatly differ from each other in terms of size, external shape and the internal anatomy. The same tissue dielectric parameters were applied for all models. The analyses suggest that the SAR difference between adults and children is more likely caused by the general differences in the head anatomy and geometry of the individuals rather than age. It seems that the external shape of the head and the distribution of different tissues within the head play a significant role in the RF energy absorption.
Absorption↗
[Salivary gland carcinomas. 1. Epidemiology, etiology, malignancy criteria, prognostic parameters and classification].
Salivary gland carcinomas comprise a rare group of malignant tumors which are difficult to diagnose and treat due to their histopathologic diversity, variable clinical course and anatomic location, particularly with respect to the facial nerve. The present paper summarizes important features of these tumors, including recent advances in their management, i.e., diagnosis, surgery of the primary tumor, neck dissection, radiation therapy, and updates risk factors, criteria of malignancy, and prognostic variables, taking into account the relevant literature. Additionally, the present paper highlights briefly the survival rates of patients suffering from salivary gland carcinomas. The present overview is divided into two parts: the first is focused on epidemiology, etiology, criteria of malignancy, prognostic factors, and tumor classification, while part II discusses the diagnosis and therapy of salivary gland carcinomas.
Carcinoma↗
[Salivary gland carcinomas Part II. Diagnosis and therapy].
Salivary gland carcinomas comprise a rare group of malignant tumors which are difficult to diagnose and treat due to their histopathologic diversity, variable clinical course and anatomic location, particularly with respect to the facial nerve. The present paper summarizes important features of these tumors, including recent advances in their management, i.e., diagnosis, surgery of the primary tumor, neck dissection, radiation therapy, and updates risk factors, criteria of malignancy, and prognostic variables, taking into account the relevant literature. Additionally, the present paper highlights briefly the survival rates of patients suffering from salivary gland carcinomas. The present overview is divided into two parts: the first is focused on epidemiology, etiology, criteria of malignancy, prognostic factors, and tumor classification, while part II discusses the diagnosis and therapy of salivary gland carcinomas.
Humans↗
Information processing in severe disorders of consciousness: vegetative state and minimally conscious state.
OBJECTIVE: To study the presence of electrophysiological indicators of remaining cortical functions in patients with persistent vegetative state (PVS) and minimally conscious state (MCS). Previous electrophysiological and PET data indicated that some PVS patients have partially intact cortical processing functions. However, it remains unclear whether the reported patients were representative for PVS population or just some exceptional cases. METHODS: Event-related brain responses to stimuli of different complexity levels, recorded in 98 patients with extremely severe diffuse brain injuries, 50 of which in PVS. Four main indicators of cortical functions were: (i) N1-P2 complex as an index of simple, undifferentiated cortical processing; (ii) mismatch negativity as an index of pre-attentive, probably unconscious, cortical orientation; (iii) P3 wave as an index of deep cortical analysis of physical stimuli, and (iv) brain responses to semantic stimuli. RESULTS: Cortical responses were found in all PVS patients with a background EEG activity > 4 Hz. All responses investigated, including those to semantic stimuli that indicated comprehension of meaning, occurred significantly above chance, though less frequently than in patients with severe brain injuries who were conscious. CONCLUSIONS: Cortical responses were lacking in most patients with severe EEG slowing (< 4 Hz). Follow-up data revealed that the presence of a mismatch negativity, a short disease duration, and the traumatic etiology were related to a better outcome. SIGNIFICANCE: The data show that in a subpopulation of PVS patients with preserved thalamocortical feedback connections, remaining cortical information processing is a consistent finding and may even involve semantic levels of processing.
Auditory Cortex↗
Single amino acid exchanges in FAD-binding domains of squalene epoxidase of Saccharomyces cerevisiae lead to either loss of functionality or terbinafine sensitivity.
Squalene epoxidase (Erg1p) is an essential enzyme in the ergosterol biosynthesis pathway in yeast. For its enzymatic activity, Erg1p requires molecular oxygen, NAD(P)H and FAD. Amino acid analysis and sequence alignment with other squalene epoxidases revealed two highly conserved FAD-binding domains, FAD I and FAD II. By random PCR mutagenesis of the ERG1 gene, one erg1 allele was isolated that carries a mutation leading to a single amino acid exchange in the FAD I domain close to the N-terminus of Erg1p. This erg1 allele codes for functional squalene epoxidase and renders yeast cells hypersensitive to terbinafine. Amino acid exchanges of other conserved residues in the FAD I and FAD II regions either led to non-functional squalene epoxidase or to the formation of squalene epoxidase with wild-type properties. These results describe the importance of specific amino acids for enzymatic activity in the yeast squalene epoxidase Erg1p.
Amino Acid Sequence↗
Lateral cervical epidural catheter placement using nerve stimulation for continuous unilateral upper extremity analgesia following a failed continuous peripheral nerve block.
This case report describes the application of electrical stimulation (Tsui test) to confirm placement of a cervical epidural catheter for postoperative pain management in a patient with a failed brachial plexus block who underwent upper extremity surgery. An epidural catheter was easily advanced under nerve stimulation guidance to the surgical dermatome C4 level without any resistance from the C7-T1 level. Successful analgesia was achieved with a bolus of 2 mg ml(-1) ropivacaine 2 ml and fentanyl 20 microg, followed by a continuous infusion of 2 mg ml(-1) ropivacaine with 2 microg ml(-1) of fentanyl at a rate of 2 ml h(-1). This case reminds the clinician that cervical epidural analgesia may serve as an alternative to a difficult continuous peripheral nerve block. Electrical stimulation may also help to confirm cervical epidural catheter placement at the appropriate dermatome to provide effective analgesia with minimal side-effects.
Amides↗
Formation and analysis of mannosylerythritol lipids secreted by Pseudozyma aphidis.
Pseudozyma aphidis DSM 70725 was found to be a novel producer of mannosylerythritol lipids (MELs). The MELs were quantified by HPLC. Glucose as carbon source for precultivation supported growth well. By contrast, at concentrations >30 g l(-1) in preculture, subsequent MEL formation in the main culture with soybean oil as sole carbon source was reduced. The type of substrate supply considerably influenced MEL formation. High concentrations of soybean oil (80 ml l(-1)) at init favored the production process when compared to a stepwise (20 ml l(-1)) addition. Mannose or erythritol were suitable second carbon sources that enhanced the MEL yield with soybean oil as preferred primary substrate. After 10 days, a maximum yield of 75 g l(-1) was attained during shake-flask cultivation. Biofuel (rapeseed oil methyl ester) also resulted in high yields of MEL, but glucose reduced the MEL yield. Analysis by GC-MS showed that all fatty acids contained in MEL and derived from soybean oil or related methyl ester were degraded by C2-units to differing extents. The surface (water/air) and interfacial (water/hexadecane) tension of the MELs produced from different carbon sources were reduced to a minimum of 26.2 mN m(-1) and 1 mN m(-1), respectively.
Glycolipids↗
Drotrecogin alfa (activated) inhibits NF-kappa B activation and MIP-1-alpha release from isolated mononuclear cells of patients with severe sepsis.
OBJECTIVE AND DESIGN: Non-anticoagulant biological activities, such as anti-inflammatory and anti-apoptotic mechanisms of action, have been suggested for recombinant human activated protein C (rhAPC; drotrecogin alfa (activated)). However, these mechanisms are much less characterized and understood than rhAPC's anticoagulant activity. Aim of the study was to determine the effect of rhAPC on the activity of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappaB) in mononuclear cells isolated from septic patients and to characterize an effect downstream from NF-kappaB activation, such as the release of the NF-kappaB-controlled chemokine Macrophage Inflammatory Protein-1-alpha (MIP-1-alpha). SUBJECTS: Peripheral blood was obtained from 13 septic patients and from 8 healthy controls. METHODS: Mononuclear cells were isolated by Ficoll-Paque density gradient centrifugation and were incubated with or without rhAPC (10 microg/ml) for 2 h for the measurement of NF-kappaB activity in cell lysates or alternatively for 6 h for the determination of MIP-1-alpha levels in supernatants. NF-kappaB activity was measured by an ELISA-based assay directed against the p50 and the p65 subunit of NF-kappaB. RESULTS: RhAPC, at supra-pharmacological concentration (10 microg/ml), significantly inhibited NF-kappaB activity and the release of MIP-1-alpha ex vivo in isolated mononuclear cells from patients with severe sepsis. In mononuclear cells of healthy subjects, however, rhAPC did not change NF-kappaB activity. Basal NF-kappaB activity early in severe sepsis was not predictive for survival. CONCLUSIONS: RhAPC at supra-pharmacological concentration (10 microg/ml) inhibits the activity of NF-kappaB in ex vivo isolated mononuclear cells of septic patients as well as the release of MIP-1-alpha, a proinflammatory chemokine regulated by NF-kappaB. These findings may represent immunomodulatory pathways by which rhAPC exerts specific anti-inflammatory activity in vitro in addition to its known anticoagulant and profibrinolytic activity and should be further investigated in an in vivo setting.
Adult↗
Profile identification of disease-associated humoral antigens using AMIDA, a novel proteomics-based technology.
We describe AMIDA (autoantibody-mediated identification of antigens), a novel target identification technology based on the immunoprecipitation of disease-specific antigens by autologous serum antibodies followed by two-dimensional electrophoretic separation, and their identification via mass spectrometry. Twenty-seven potential carcinoma antigens were identified including proteins of hitherto unknown function. Validation of one of the identified antigens, cytokeratin 8, revealed its de novo expression in hyperplastic tissue, gradual overexpression with increasing malignancy, and ectopic localization on the cell surface. Furthermore, a strong prevalence of CK8-specific antibodies occurred in the serum of cancer patients already at early disease stages. In situ hybridization for one marker of unknown function, KIAA1273/TOB3, demonstrated its strong overexpression in head and neck carcinomas, thus making it a likely tumor antigen candidate. Eventually, AMIDA could foster significant improvements for the diagnosis and therapy of human diseases eliciting a humoral immune response, and allows for the rapid identification of new target molecules.
Allergy and Immunology↗
[Regression of oesophageal carcinomas after neoadjuvant radiochemotherapy: criteria of the histopathological evaluation].
Following surgical resection locally advanced oesophageal carcinomas exhibit a bad prognosis and therefore neoadjuvant therapeutic strategies were developed. Because success of therapy is associated with the extent of tumor regression in this context, the introduction of objective histopathological criteria seems to be very important. This study included 67 patients with oesophageal carcinomas (cT2-cT4 cNx cM0) that were treated with a cisplatin- and 5-fluorouracil-containing simultaneous radiochemotherapy. In 43 patients squamous cell, in 24 cases adenocarcinomas were diagnosed. After completion of therapy, a surgical resection and a histopathological examination of the tissue specimens were performed. The extent of tumor regression was histologically evaluated and therapy-induced alterations were graded semiquantitatively. Thereby, a significantly favorable prognosis was observed in the group of patients that showed a regression of carcinomas of 90% or more. Additionally, the extent of a resorptive-histiocytic reaction, giant cells and lymphocytic infiltrates correlated with the grade of regression. These results underline the importance of an exact examination and histomorphological evaluation of the response for the assessment of survival probability after neoadjuvant radiochemotherapy of oesophageal carcinomas.
Antineoplastic Combined Chemotherapy Protocols↗
Evaluation of PCR in the molecular diagnosis of endocarditis.
OBJECTIVE: Infective endocarditis (IE) is diagnosed by the Duke criteria, which can be inconclusive particularly when blood cultures are negative. This study investigated the application of polymerase chain reaction (PCR) to identify bacterial DNA in excised valvular tissue, and its role in establishing the diagnosis of IE. METHODS: Ninety-eight patients undergoing valve replacement surgery were studied. Twenty-eight patients were confirmed as definite for endocarditis by the Duke criteria; nine were considered as possible and 61 had no known or previous microbial infection of the endocardium. A broad-range PCR technique was used to amplify prokaryotic 16S rRNA genes present within homogenised heart valve tissue. Subsequent DNA sequencing of the PCR amplicon allowed identification of the infecting microorganism. RESULTS: PCR results demonstrated the presence of bacterial DNA in the heart valves obtained from 14 out of 20 (70%) definite IE patients with positive blood cultures preoperatively. The causative microorganism for one patient with definite culture negative endocarditis was identified by PCR. Two out of nine (22%) of the valves from possible endocarditis patients also had bacterial DNA present converting them into the definite criteria whereas in the valves of seven out of nine (78%) of these patients no bacterial DNA was detected. CONCLUSION: The application of PCR to the explanted valves in patients with possible or confirmed diagnosis can augment the Duke criteria thereby improving post-surgical antimicrobial therapeutic options.
Adult↗