[Potential effect of the stimulus threshold level of the nociceptive flexion reflex (NFRT) on mortality and delirium incidence in the critically ill patient: a retrospective cohort analysis]. / Potenzieller Einfluss der Reizschwellenhöhe des nozizeptiven Flexorenreflex (NFRT) auf die Mortalitäts- und Delirinzidenz beim kritisch kranken Patienten: eine retrospektive Kohortenanalyse.

BACKGROUND: Mortality and delirium in critically ill patients are affected by the provided analgesics and sedatives. The deeper the sedation and the higher the dose of analgesics applied, the more difficult it is to assess pain and the depth of sedation. Therefore, instrumental measurement methods, such as the measurement of the stimulus threshold of the nociceptive flexion reflex (NFRT), are becoming increasingly more important. OBJECTIVE: The aim of the present study is to investigate a potential association between the level of the nociceptive flexion reflex, mortality, and the occurrence of delirium. MATERIAL AND METHODS: By retrospectively analyzing a pilot data set of 57 ICU patients from the interdisciplinary surgical ICU of Ulm University Hospital surveyed between 11/2018 and 03/2020, a possible association between the NFRT, mortality, and the occurrence of delirium was calculated in an adjusted logistic regression model. Depending on the cut-off value, the stimulus threshold corridors result in the following comparison pairs: < 20 mA vs. 20-40 mA/20-50 mA/20-60 mA, > 40 mA vs. 20-40 mA, > 50 mA vs. 20-50 mA and > 60 mA vs. 20-60 mA. Results are presented as odds ratios (OR) adjusted for age, sex, height, TISS-28, SAPS II, RASS, BPS, and applied analgesics. Pain assessment was performed, in addition to the Behavioral Pain scale, ≥ 3 times daily by measuring NFRT. RESULTS: A statistically nonsignificant tendency for an increase in mortality incidence occurred with an NFRT > 50 mA, versus a stimulus threshold corridor of 20-50 mA (OR 3.3, CI: 0.89-12.43, p = 0.07). A trend toward a reduction in delirium incidence occurred at an NFRT < 20 mA, versus a stimulus threshold corridor of 20-40 mA (OR 0.40, CI: 0.18-0.92, p = 0.03). CONCLUSION: Based on the level of the NFRT, no recommendation can be made at this point to adjust the analgesic regimen of critically ill patients, who are unable to communicate. The observation of a tendency towards an increase in mortality at high stimulus thresholds or a reduction in the occurrence of delirium at low stimulus thresholds of the NFRT must be verified in standardized studies.

Targeting Epilepsy Through the Foremen Ovale: How Many Helical Needles are Needed?

Laser ablation of the hippocampus offers medically refractory epilepsy patients an alternative to invasive surgeries. Emerging commercial solutions deliver the ablator through a burr hole in the back of the head. We recently introduced a new access path through the foremen ovale, using a helical needle, which minimizes the amount of healthy brain tissue the needle must pass through on its way to the hippocampus, and also enables the needle to follow the medial axis of the hippocampus more closely. In this paper, we investigate whether helical needles should be designed and fabricated on a patient-specific basis as we had previously proposed, or whether a small collection of pre-defined needle shapes can apply across many patients. We propose a new optimization strategy to determine this needle set using patient data, and investigate the accuracy with which these needles can reach the the medial axis of the hippocampus. We find that three basic tube shapes (mirrored as necessary for left vs. right hippocampi) are all that is required, across 20 patient datasets (obtained from 10 patient CT scans), to reduce worst-case maximum error below 2 mm.

Development of a PET/EPRI combined imaging system for assessing tumor hypoxia.

Precise quantitative delineation of tumor hypoxia is essential in radiation therapy treatment planning to improve the treatment efficacy by targeting hypoxic sub-volumes. We developed a combined imaging system of positron emission tomography (PET) and electron para-magnetic resonance imaging (EPRI) of molecular oxygen to investigate the accuracy of PET imaging in assessing tumor hypoxia. The PET/EPRI combined imaging system aims to use EPRI to precisely measure the oxygen partial pressure in tissues. This will evaluate the validity of PET hypoxic tumor imaging by (near) simultaneously acquired EPRI as ground truth. The combined imaging system was constructed by integrating a small animal PET scanner (inner ring diameter 62 mm and axial field of view 25.6 mm) and an EPRI subsystem (field strength 25 mT and resonant frequency 700 MHz). The compatibility between the PET and EPRI subsystems were tested with both phantom and animal imaging. Hypoxic imaging on a tumor mouse model using 18F-fluoromisonidazole radio-tracer was conducted with the developed PET/EPRI system. We report the development and initial imaging results obtained from the PET/EPRI combined imaging system.

Biological screening of extracts from leaf and stem bark of Croton floribundus Spreng. (Euphorbiaceae) / Triagem biológica de extratos das folhas e caules de Croton floribundus Spreng. (Euphorbiaceae)

Abstract This work describes the preliminary evaluation of cytotoxic, antimicrobial, molluscicidal, antioxidant and anticholinesterase activities from leaf (LECF) and stem bark alcoholic extracts (BECF) of the species Croton floribundus Spreng. (Euphorbiaceae), popularly known as capixingui or tapixingui. BECF presented significant toxicity (LC50 = 89.6 μg/ml) in the Artemia salina Leach, 1819 (Crustacea: Branchiopoda) bioassay, whereas LECF did not show activity (LC50 > 1000 μg/ml). From DPPH method, the values of IC50 for the LECF and BECF were 61.2 μg/ml and 62.2 μg/ml, respectively, showing that C. floribundus has an expressive antioxidant activity. Antimicrobial susceptibility was evaluated by microdilution technique and only BECF was active against Staphylococcus aureus (MIC = 39.6 μg/ml). The extracts did not present molluscicidal activity against snail Biomphalaria glabrata Say, 1818 (Gastropoda: Planorbidae). Both extracts revealed the presence of several components with an inhibiting capacity of acetylcholinesterase enzyme on the bioautographic assay. C. floribundus showed to be a promising species considering that it exhibited good biological activity in the most assays performed.

Resumo Este trabalho descreve a avaliação preliminar das atividades citotóxica, antimicrobiana, moluscicida, antioxidante e anticolinesterásica de extratos alcoólicos das folhas (LECF) e das cascas do caule (BECF) da espécie Croton floribundus Spreng. (Euphorbiaceae), popularmente conhecida como capixingui ou tapixingui. No bioensaio com Artemia salina Leach, 1819 (Crustacea: Branchiopoda), BECF apresentou toxicidade significante (LC50 = 89,6 µg/ml), enquanto que LECF não apresentou atividade (LC50 > 1000 µg/ml). A partir do método de DPPH, os valores de IC50 para o LECF e BECF foram 61,2 µg/ml e 62,2 µg/ml, respectivamente, evidenciando que C. floribundus tem uma atividade antioxidante expressiva. A susceptibilidade antimicrobiana foi avaliada pela técnica de microdiluição e apenas BECF foi ativo contra Staphylococcus aureus (MIC = 39,6 mg/ml). Os extratos não apresentaram atividade moluscicida contra o caramujo Biomphalaria glabrata Say, 1818 (Gastropoda: Planorbidae). Ambos os extratos revelaram a presença de componentes com capacidade inibidora da enzima acetilcolinesterase no ensaio bioautográfico. C. floribundus mostrou ser uma espécie promissora considerando que exibiu boa atividade biológica na maioria dos ensaios testados.

Biological screening of extracts from leaf and stem bark of Croton floribundus Spreng. (Euphorbiaceae).

This work describes the preliminary evaluation of cytotoxic, antimicrobial, molluscicidal, antioxidant and anticholinesterase activities from leaf (LECF) and stem bark alcoholic extracts (BECF) of the species Croton floribundus Spreng. (Euphorbiaceae), popularly known as capixingui or tapixingui. BECF presented significant toxicity (LC50 = 89.6 µg/ml) in the Artemia salina Leach, 1819 (Crustacea: Branchiopoda) bioassay, whereas LECF did not show activity (LC50 > 1000 µg/ml). From DPPH method, the values of IC50 for the LECF and BECF were 61.2 µg/ml and 62.2 µg/ml, respectively, showing that C. floribundus has an expressive antioxidant activity. Antimicrobial susceptibility was evaluated by microdilution technique and only BECF was active against Staphylococcus aureus (MIC = 39.6 µg/ml). The extracts did not present molluscicidal activity against snail Biomphalaria glabrata Say, 1818 (Gastropoda: Planorbidae). Both extracts revealed the presence of several components with an inhibiting capacity of acetylcholinesterase enzyme on the bioautographic assay. C. floribundus showed to be a promising species considering that it exhibited good biological activity in the most assays performed.

Mesenchymal stem cells in peripheral blood of severely injured patients.

PURPOSE: Mesenchymal stem cells (MSCs) are primarily stromal cells present in bone marrow and other tissues that are crucial for tissue regeneration and can be mobilized into peripheral blood after different types of organ damage. However, little is known about MSC appearance in blood in the setting of polytrauma. METHODS: We conducted a monocentered and longitudinal observational clinical study in 11 polytraumatized patients with an injury severity score (ISS) ≥ 24 to determine the numbers of MSCs in peripheral blood. Blood was collected from healthy volunteers and patients after polytrauma in the emergency room and 4, 12, 24, 48 h, 5 and 10 day later, and cells carrying MSC-surface markers (negative for CD45, positive for CD29, CD73, CD90, CD105, and CD166 in different combinations also employing the more stringent markers STRO1 and MSCA1) were detected and characterized using flow cytometry. Relative numbers of MSC-like cells were correlated with clinical parameters to evaluate if specific injury patterns had an influence on their presence in the blood cell pool. RESULTS: We were able to detect MSC marker-positive cells in both cohorts; however, the percentage of those cells present in the blood of patients during the first 10 day after injury was mostly similar to healthy volunteers, and significantly lowers starting at 4 h post trauma for one marker combination when compared to controls. Furthermore, the presence of a pelvis fracture was partly correlated with reduced relative numbers of MSC-like cells detectable in blood. CONCLUSIONS: Polytrauma in humans was associated with partly reduced relative numbers of MSC-like cells detected in peripheral blood in the time course after injury. Further studies need to define if this reduction was due to lower mobilization from the bone marrow or to active migration to the sites of injury.

Complement C5a-Induced Changes in Neutrophil Morphology During Inflammation.

The complement and neutrophil defence systems, as major components of innate immunity, are activated during inflammation and infection. For neutrophil migration to the inflamed region, we hypothesized that the complement activation product C5a induces significant changes in cellular morphology before chemotaxis. Exposure of human neutrophils to C5a dose- and time-dependently resulted in a rapid C5a receptor-1 (C5aR1)-dependent shape change, indicated by enhanced flow cytometric forward-scatter area values. Similar changes were observed after incubation with zymosan-activated serum and in blood neutrophils during murine sepsis, but not in mice lacking the C5aR1. In human neutrophils, Amnis high-resolution digital imaging revealed a C5a-induced decrease in circularity and increase in the cellular length/width ratio. Biomechanically, microfluidic optical stretching experiments indicated significantly increased neutrophil deformability early after C5a stimulation. The C5a-induced shape changes were inhibited by pharmacological blockade of either the Cl-/HCO3--exchanger or the Cl- -channel. Furthermore, actin polymerization assays revealed that C5a exposure resulted in a significant polarization of the neutrophils. The functional polarization process triggered by ATP-P2X/Y-purinoceptor interaction was also involved in the C5a-induced shape changes, because pretreatment with suramin blocked not only the shape changes but also the subsequent C5a-dependent chemotactic activity. In conclusion, the data suggest that the anaphylatoxin C5a regulates basic neutrophil cell processes by increasing the membrane elasticity and cell size as a consequence of actin-cytoskeleton polymerization and reorganization, transforming the neutrophil into a migratory cell able to invade the inflammatory site and subsequently clear pathogens and molecular debris.

Evaluation of [Formula: see text] enrichment values obtained with an oral breath test under conditions of impaired gastric functioning.

Gastric emptying can be assessed by an oral administration of a 13C labeled substrate and its response in the expiratory release of the oxidation product [Formula: see text]. Impaired gut function, reflected, for example, in an intolerance against enteral nutrition may delay or discontinue gastric emptying, potentially leading to multiple peaks in the time profile of expiration. The resulting profile cannot be analyzed by the usual data evaluation that is based on a 'beta exponential' (BEX) function. We developed a new approach that better reflects the underlying physiology. It allows a flexible time profile of gastric release and considers a transient [Formula: see text] retention in different compartments as well as an incomplete recovery of [Formula: see text] in the expiration. Parameters that describe the distribution/retention kinetics cannot be determined based on the same breath data that were used to estimate emptying. To enable the determination of the kinetic parameters, they were constrained to match published data using a Bayesian statistical analysis. The applicability of the new model was compared with BEX for healthy subjects. BEX fails to explain the observed data and, compared to the new approach, overestimates the speed of emptying. Predictive accuracy under impaired gastric motility was explored using synthetic data. Only the new approach can reproduce a multiphase absorption profile. When routine benchtop equipment was used for measurements, then the rate-limiting step for precision in the estimate of emptying is the quality in the a priori estimate for kinetic parameters rather than precision in measurements. Only about 80% of the absorbed [Formula: see text] has to be released by expiration. With these features, the new approach promises to widen the applicability of breath tests for gastric emptying.

Biological screening of extracts from leaf and stem bark of Croton floribundus Spreng. (Euphorbiaceae)

Abstract This work describes the preliminary evaluation of cytotoxic, antimicrobial, molluscicidal, antioxidant and anticholinesterase activities from leaf (LECF) and stem bark alcoholic extracts (BECF) of the species Croton floribundus Spreng. (Euphorbiaceae), popularly known as capixingui or tapixingui. BECF presented significant toxicity (LC50 = 89.6 g/ml) in the Artemia salina Leach, 1819 (Crustacea: Branchiopoda) bioassay, whereas LECF did not show activity (LC50 > 1000 g/ml). From DPPH method, the values of IC50 for the LECF and BECF were 61.2 g/ml and 62.2 g/ml, respectively, showing that C. floribundus has an expressive antioxidant activity. Antimicrobial susceptibility was evaluated by microdilution technique and only BECF was active against Staphylococcus aureus (MIC = 39.6 g/ml). The extracts did not present molluscicidal activity against snail Biomphalaria glabrata Say, 1818 (Gastropoda: Planorbidae). Both extracts revealed the presence of several components with an inhibiting capacity of acetylcholinesterase enzyme on the bioautographic assay. C. floribundus showed to be a promising species considering that it exhibited good biological activity in the most assays performed.

Resumo Este trabalho descreve a avaliação preliminar das atividades citotóxica, antimicrobiana, moluscicida, antioxidante e anticolinesterásica de extratos alcoólicos das folhas (LECF) e das cascas do caule (BECF) da espécie Croton floribundus Spreng. (Euphorbiaceae), popularmente conhecida como capixingui ou tapixingui. No bioensaio com Artemia salina Leach, 1819 (Crustacea: Branchiopoda), BECF apresentou toxicidade significante (LC50 = 89,6 µg/ml), enquanto que LECF não apresentou atividade (LC50 > 1000 µg/ml). A partir do método de DPPH, os valores de IC50 para o LECF e BECF foram 61,2 µg/ml e 62,2 µg/ml, respectivamente, evidenciando que C. floribundus tem uma atividade antioxidante expressiva. A susceptibilidade antimicrobiana foi avaliada pela técnica de microdiluição e apenas BECF foi ativo contra Staphylococcus aureus (MIC = 39,6 mg/ml). Os extratos não apresentaram atividade moluscicida contra o caramujo Biomphalaria glabrata Say, 1818 (Gastropoda: Planorbidae). Ambos os extratos revelaram a presença de componentes com capacidade inibidora da enzima acetilcolinesterase no ensaio bioautográfico. C. floribundus mostrou ser uma espécie promissora considerando que exibiu boa atividade biológica na maioria dos ensaios testados.

Percutaneous left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation and contraindication for anticoagulation.

BACKGROUND: Stroke, as the third cause of death in developed countries, is a public health issue. Atrial fibrillation is an important cause of ischemic stroke and its prevention is efficient with oral anticoagulation. However, oral anticoagulation can be contraindicated because of hemorrhagic risk related to these treatments. Percutaneous left atrial appendage occlusion is a new alternative of oral anticoagulation for patients with atrial fibrillation and high risk of cardio-embolic stroke but contraindicated for oral anticoagulation. METHODS: We describe in this paper the procedure of left atrial appendage occlusion with the Amplatzer cardiac plug device, used in our center in Grenoble university hospital, for the first three patients who have been treated with this device. These three patients (one man and two women) have all atrial fibrillation with neurological complication of this arrhythmia, as ischemic stroke. Oral anticoagulation is indicated to prevent another ischemic stroke. However, they all have a high risk of cerebral bleeding for different reasons (cavernomatosis, history of intracerebral hemorrhage and aneurysm of the polygon of Willis). Consequently, they have a high risk of cardio-embolic complication but contraindication for oral anticoagulation. They have been treated by left atrial appendage occlusion with Amplatzer cardiac plug device by percutaneous and trans-septal access. Then, they have been followed by neurologist and cardiologist, with clinical and paraclinical evaluation by echocardiography. RESULTS: Our three first patients have been successfully implanted, without periprocedural complication. No latest adverse event was observed, and particularly no cardiac or neurologic adverse event. CONCLUSION: The technique of left atrial appendage occlusion is a very interesting and promising technique for ischemic stroke prevention in patient with high risk of cardio-embolic complication because of atrial fibrillation, but high risk of bleeding and contraindication for oral anticoagulation. Because of frequency of both atrial fibrillation and contraindication for oral anticoagulation, occlusion of the left atrial appendage should become an interesting alternative for many patients. However, it remains an invasive procedure and efficacy and indications need to be evaluated in further clinical trials. Risk/benefit ratio must be carefully assessed and compared to that of the new anticoagulant drugs.

EUROPattern Suite technology for computer-aided immunofluorescence microscopy in autoantibody diagnostics.

Antinuclear autoantibodies (ANA) are highly informative biomarkers in autoimmune diagnostics. The increasing demand for effective test systems, however, has led to the development of a confusingly large variety of different platforms. One of them, the indirect immunofluorescence (IIF), is regarded as the common gold standard for ANA screening, as described in a position statement by the American College of Rheumatology in 2009. Technological solutions have been developed aimed at standardization and automation of IIF to overcome methodological limitations and subjective bias in IIF interpretation. In this review, we present the EUROPattern Suite, a system for computer-aided immunofluorescence microscopy (CAIFM) including automated acquisition of digital images and evaluation of IIF results. The system was originally designed for ANA diagnostics on human epithelial cells, but its applications have been extended with the latest system update version 1.5 to the analysis of antineutrophil cytoplasmic antibodies (ANCA) and anti-dsDNA antibodies.

ESR Microscopy for Biological and Biomedical Applications.

We report on electron-spin resonance microscopy (ESRM) providing sub-micron resolution (~700nm) with a high spin concentration sample, i.e. lithium phthalocyanine (LiPc) crystal. For biomedical applications of our ESRM, we have imaged samples containing rat basophilic leukemia (RBL) cells as well as cancerous tissue samples with a resolution of several microns using a water soluble spin probe, Trityl_OX063_d24. Phantom samples with the nitroxide spin label, (15)N PDT, were also imaged to demonstrate that nitroxides, which are commonly used as spin labels, may also be used for ESRM applications. ESRM tissue imaging would therefore be valuable for diagnostic or therapeutic purposes. Also, ESRM can be used to study the motility or the metabolism of cells in various environments. With further modification and/or improvement of imaging probe and spectrometer instrumentation sub-micron biological images should be obtainable, thereby providing a useful tool for various biomedical applications.

A Case of Autoimmune Hepatitis Treated with Rituximab.

Autoimmune hepatitis (AIH) is a form of chronic hepatitis of unknown etiology. It was first described in the 1950s as a form of chronic hepatitis noted in younger women. It was later termed lupoid hepatitis due to its association with autoantibodies before being named AIH in 1965. Corticosteroids and azathioprine have been the standard therapy for AIH, but due to treatment failures and toxicities from these medications, new medications are being investigated as possible treatment options. Rituximab has been used in various autoimmune disorders with good success. We report the case of a 34-year-old Caucasian woman with a history of B cell lymphoma and concurrent AIH treated with rituximab. The diagnosis of AIH was made by classic serological and histological features. The patient was initially treated with steroids but had a progression of her disease as well as suffering toxicities from the steroids. She was then given eight weeks of rituximab with good improvement in both laboratory and histological findings.

A new method of monitoring osteomyelitis.

Chronic infections of bone such as osteomyelitis are frequent events, especially in immunocompromised or diabetic patients, and costly on a national level. Incorrect treatment or delayed diagnosis may lead to loss of the affected extremity or mandible. The aim of this study was to assess the possible value of urinary lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) concentrations in the monitoring of mandibular osteomyelitis. Patients were assigned to the following groups: group 1 (n=85), control; group 2a (n=38), patients with active disease; group 2b (n=25), patients of group 2a 6 months after successful treatment; group 2c (n=7), patients of group 2a with ongoing osteomyelitis 6 months after treatment. The range and upper limit of normal values (HP(max) and LP(max)) were determined in group 1. Levels of LP and HP were measured by high-performance liquid chromatography and fluorescence detection. There was a significant decrease (mean 45.43% for HP and 32.12% for LP) in samples of group 2b compared to 2a (P<0.001 for HP and LP). There was a significant increase in HP values in samples from group 2c compared to 2a (P=0.018). The urinary concentrations of HP and LP appear to act as a marker of disease activity, with a decrease reflecting treatment success and an increase or stable values indicating persistent disease. An inexpensive tool (US$5 per analysis) for the monitoring of osteomyelitis is described.

The use of a new 3D splint and double CT scan procedure to obtain an accurate anatomic virtual augmented model of the skull.

Three-dimensional (3D) virtual planning of orthognathic surgery requires detailed visualization of the interocclusal relationship. The purpose of this study was to introduce the modification of the double computed tomography (CT) scan procedure using a newly designed 3D splint in order to obtain a detailed anatomic 3D virtual augmented model of the skull. A total of 10 dry adult human cadaver skulls were used to evaluate the accuracy of the automatic rigid registration method for fusion of both CT datasets (Maxilim, version 1.3.0). The overall mean registration error was 0.1355+/-0.0323 mm (range 0.0760-0.1782 mm). Analysis of variance showed a registration method error of 0.0564 mm (P < 0.001; 95% confidence interval = 0.0491-0.0622). The combination of the newly designed 3D splint with the double CT scan procedure allowed accurate registration and the set-up of an accurate anatomic 3D virtual augmented model of the skull with detailed dental surface.

[Recurrent tumors in the oral and maxillofacial region. Results and treatment strategies in 20 years]. / Tumorrezidive im Mund- Kiefer- und Gesichtsbereich. Ergebnisse und Therapiestrategien in 20 Jahren.

UNLABELLED: SUBJECT MATTER: Following clinical diagnosis of a recurrent tumor, curative treatment is seldom available. Depending on the size of the recurrent tumor and the patient's general health condition, extensive surgical resections and reconstructions are avoided in favor of nonsurgical treatment modalities with palliative intent. According to the literature, location of the tumor, tumor size and R-1 and R-2 resection rates are the most frequent reasons for the development of recurrent tumors. PATIENTS AND METHODS: In a retrospective evaluation, a population of 1000 patients who had been treated for primary head and neck cancer during the period from 1979 to 1996 were analyzed descriptively. Survival probabilities of patients with recurrent tumors were calculated according to the Kaplan-Meier product-limit method, and different treatment concepts were compared and analyzed with the log-rank test for significant differences. RESULTS: The largest proportion of primary tumors involved the floor of the mouth (n=369, 36.9%). A total of 198 patients (19.8%) developed recurrent cancer; 79.8% of patients experienced recurrent cancer within 2 years following primary treatment. Within the group of T1/T2 tumors the incidence of recurrent tumors was 28.9%, whereas the incidence in the T3/T4 group was 44.6%. Tumor infiltration of the resection margins was detected in 12.9%. CONCLUSIONS: In line with the literature, tumor infiltration of the resection margins is a relevant prognostic factor; therefore, intraoperative frozen section must be recommended. Treatment with curative intention, in particular extensive surgical resections, is seldom possible and always requires a very intensive discussion with the patient.

Recurrent carcinoma of the head and neck: treatment strategies and survival analysis in a 20-year period.

Following clinical diagnosis of a recurrent tumor, curative treatment is seldom available. Depending on the size of the recurrent tumor and the patient's general health condition extensive surgical resections and reconstructions are avoided in favor of non-surgical palliative intended treatment modalities. According to the literature location of the tumor, tumor size, as well as R-1- and R-2-resection rates are the most frequent reasons for the development of recurrent tumors. In a retrospective evaluation a population of 1000 patients who were treated for a primary head and neck cancer during the period from 1979 to 1996 were analysed descriptively. Survival probabilities of patients with recurrent tumors were calculated according to the product-limit method by Kaplan-Meier, different treatment concepts were compared and analysed with the log-rank test for significant differences. The largest proportion of primary tumors involved the floor of mouth ( n = 369, 36.9%). A total of 198 patients (19.8%) developed a recurrent cancer; 79.8% of patients experienced a recurrent cancer within two years following primary treatment. Within the group of T1/T2 tumors the incidence of recurrent tumors was 28.9%, whereas the incidence in the T3/T4 group was 44.6%. Tumor infiltration of the resection margins was detected in 12.9%. In line with the literature, tumor infiltration of the resection margins is a relevant prognostic factor, therefore intraoperative frozen section must be recommended. Treatment with curative intention, in particular extensive surgical resections, is seldom possible, and requires always a very intensive discussion with the patient.

Phenylalanine kinetics in healthy volunteers and liver cirrhotics: implications for the phenylalanine breath test.

Expired 13CO2 recovery from an oral l-[1-13C]phenylalanine ([13C]Phe) dose has been used to quantify liver function. This parameter, however, does not depend solely on liver function but also on total CO2 production, Phe turnover, and initial tracer distribution. Therefore, we evaluated the impact of these factors on breath test values. Nine ethyl-toxic cirrhotic patients and nine control subjects received intravenously 2 mg/kg of [13C]Phe, and breath and blood samples were collected over 4 h. CO2 production was measured by indirect calorimetry. The exhaled 13CO2 enrichments were analyzed by isotope ratio mass spectrometry and the [13C]Phe and l-[1-13C]tyrosine enrichments by gas chromatography-mass spectrometry. The cumulative 13CO2 recovery was significantly lower in cirrhotic patients (7 vs. 12%; P < 0.01), in part due to lower total CO2 production rates. Phe turnover in cirrhotic patients was significantly lower (33 vs. 44 micro mol. kg(-1). h(-1); P < 0.05). When these extrahepatic factors were considered in the calculation of the Phe oxidation rate, the intergroup differences were even more pronounced (3 vs. 7 micro mol. kg(-1). h(-1)) than those for 13CO2 recovery data. Also, the Phe-to-Tyr conversion rate, another indicator of Phe oxidation, was significantly reduced (0.7 vs. 3.0 micro mol. kg(-1). h(-1)).

Electron spin relaxation of triarylmethyl radicals in fluid solution.

Electron spin relaxation times of a Nycomed triarylmethyl radical (sym-trityl) in water, 1:1 water:glycerol, and 1:9 water:glycerol were measured at L-band, S-band, and X-band by pulsed EPR methods. In H(2)O solution, T(1) is 17+/-1 micros at X-band at ambient temperature, is nearly independent of microwave frequency, and exhibits little dependence on viscosity. The temperature dependence of T(1) in 1:1 water:glycerol is characteristic of domination by a Raman process between 20 and 80 K. The increased spin-lattice relaxation rates at higher temperatures, including room temperature, are attributed to a local vibrational mode that modulates spin-orbit coupling. In H(2)O solution, T(2) is 11+/-1 micros at X-band, increasing to 13+/-1 micros at L-band. For more viscous solvent mixtures, T(2) is much shorter than T(1) and weakly frequency dependent, which indicates that incomplete motional averaging of hyperfine anisotropy makes a significant contribution to T(2). In water and 1:1 water:glycerol solutions continuous wave EPR linewidths are not relaxation determined, but become relaxation determined in the higher viscosity 1:9 water:glycerol solutions. The Lorentzian component of the 250-MHz linewidths as a function of viscosity is in good agreement with T(2)-determined contributions to the linewidths at higher frequencies.

Differences in the expression of CD64 and mCD14 on polymorphonuclear cells and on monocytes in patients with septic shock.

The present study was performed to clarify the time course of the expression of CD64, the Fc gamma receptor type I (FcgammaR1), and membrane-bound CD14 (mCD14), one of the major receptors for endotoxin, on polymorphonuclear leukocytes (PMN) and monocytes in 22 postoperative/post-traumatic patients with septic shock. Therefore, the expression of CD64 and mCD14, and serum concentrations of granulocyte colony-stimulating factor (G-CSF) and interferon-gamma (IFN-gamma) were determined by flow cytometric analysis and enzyme-linked immunosorbent assay (ELISA), respectively, from the first day of septic shock onwards over a period of 14 days. When compared to the values of 12 healthy controls, CD64 expression was elevated significantly on PMN and monocytes of the patients, whereas the expression of mCD14 was decreased significantly at all days. The initially increased expression of CD64 on PMN and monocytes decreased within the first days of septic shock. The already initially decreased mCD14 expression decreased further on PMN, but not on monocytes. Serum concentrations of G-CSF and IFN-gamma during the study period were significantly higher than those of the control group. The differences in the kinetics of CD64 and mCD14 expression in patients with septic shock may be explained by different regulatory effects of cytokines, such as G-CSF and IFN-gamma.