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Background: Transoral laser microsurgery, the standard surgical approach for early-stage laryngeal cancer, necessitates an unobstructed line of sight to the operating field. However, achieving adequate laryngeal exposure can be challenging, potentially compromising treatment outcomes., Methods: We developed a 3D-printed curved laryngoscope (sMAC), designed to match the upper airway anatomy. In a user study (n = 15) with a human body donor we compared the sMAC system to conventional microlaryngoscopy regarding laryngeal exposure and accessibility in a difficult exposure scenario., Results: All 15 participants achieved complete glottic exposure and successfully manipulated laryngeal landmarks using the sMAC system. Only four participants achieved partial exposure using microlaryngoscopy. Positioning of the sMAC system was significantly faster (p = 0.023). A vocal cord resection was conducted successfully (n = 2) using the sMAC system., Conclusion: The sMAC system effectively addresses challenges associated with transoral laryngeal surgery. Ongoing development aims to overcome current limitations of the system and prepare first clinical trials., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Background: Acute kidney injury (AKI) is highly prevalent in critical COVID-19 patients. The diagnosis and staging of AKI are based on serum creatinine (sCr) and urinary output criteria, with limitations in the functional markers. New cell-cycle arrest biomarkers [TIMP2]*[IGFBP7] have been proposed for early detection of AKI, but their role in critically ill COVID-19 patients is poorly understood., Methods: We conducted an observational study to assess the performance of [TIMP2]*[IGFBP7] for the detection of AKI in critical COVID-19 patients admitted to our intensive care unit (ICU). We sampled urinary [TIMP2]*[IGFBP7] levels at ICU admission, 12 h, 24 h, and 48 h, and compared the results to the development of AKI, as well as baseline and laboratory data., Results: Forty-one patients were enrolled. The median age was 66 years [57-72] and most were males (85%). Thirteen patients (31.7%) developed no/mild stage AKI, 19 patients (46.3%) moderate AKI, and nine patients (22.0%) severe AKI. The ICU mortality was 29.3%. sCr levels in the Emergency Department or at ICU admission were not significantly different according to AKI stage. [TIMP-2]*[IGFBP-7] urinary levels were elevated in severe AKI at 12 h after ICU admission, but not at ICU admission or 24 h or 48 h after ICU admission., Conclusion: Urinary biomarkers [TIMP-2]*[IGFBP-7] were generally increased in this population with a high prevalence of AKI, and were higher in patients with severe AKI measured at 12 h from ICU admission. Further studies are needed to evaluate the best timing of these biomarkers in this population.

Microvascular procedures require visual magnification of the surgical field, e.g. by a microscope. This can be accompanied by an unergonomic posture with musculoskeletal pain or long-term degenerative changes as the eye is bound to the ocular throughout the whole procedure. The presented study describes the advantages and drawbacks of a 3D exoscope camera system. The RoboticScope ® -system (BHS Technologies ® , Innsbruck, Austria) features a high-resolution 3D-camera that is placed over the surgical field and a head-mounted-display (HMD) that the camera pictures are transferred to. A motion sensor in the HMD allows for hands-free change of the exoscope position via head movements. For general evaluation of the system functions coronary artery anastomoses of ex-vivo pig hearts were performed. Second, the system was evaluated for anastomosis of a radial-forearm-free-flap in a clinical setting/in vivo. The system positioning was possible entirely hands-free using head movements. Camera control was intuitive; visualization of the operation site was adequate and independent from head or body position. Besides technical instructions of the providing company, there was no special surgical training of the surgeons or involved staff upfront performing the procedures necessary. An ergonomic assessment questionnaire showed a favorable ergonomic position in comparison to surgery with a microscope. The outcome of the operated patient was good. There were no intra- or postoperative complications. The exoscope facilitates a change of head and body position without losing focus of the operation site and an ergonomic working position. Repeated applications have to clarify if the system benefits in clinical routine., (© 2021. The Author(s).)

Background: Mas gene-related G protein-coupled receptors (MRGPRs) are a G protein-coupled receptor family responsive to various exogenous and endogenous agonists, playing a fundamental role in pain and itch sensation. The primate-specific family member MRGPRX2 and its murine orthologue MRGPRB2 are expressed by mast cells mediating IgE-independent signaling and pseudoallergic drug reactions., Objectives: Our aim was to increase knowledge about the function and regulation of MRGPRX2/MRGPRB2, which is of major importance in prevention of drug hypersensitivity reactions and drug-induced pruritus., Methods: To identify novel MRGPR (ant)agonists, we screened a library of pharmacologically active compounds by utilizing a high-throughput calcium mobilization assay. The identified hit compounds were analyzed for their pseudoallergic and pruritogenic effects in mice and human., Results: We found a class of commonly used drugs activating MRGPRX2 that, to a large extent, consists of antidepressants, antiallergic drugs, and antipsychotics. Three-dimensional pharmacophore modeling revealed structural similarities of the identified agonists, classifying them as cationic amphiphilic drugs. Mast cell activation was investigated by using the 3 representatively selected antidepressants clomipramine, paroxetine, and desipramine. Indeed, we were able to show a concentration-dependent activation and MRGPRX2-dependent degranulation of the human mast cell line LAD2 (Laboratory of Allergic Diseases-2). Furthermore, clomipramine, paroxetine, and desipramine were able to induce degranulation of human skin and murine peritoneal mast cells. These substances elicited dose-dependent scratching behavior following intradermal injection into C57BL/6 mice but less so in MRGPRB2-mutant mice, as well as wheal-and-flare reactions following intradermal injections in humans., Conclusion: Our results contribute to the characterization of structure-activity relationships and functionality of MRGPRX2 ligands and facilitate prediction of adverse reactions such as drug-induced pruritus to prevent severe drug hypersensitivity reactions., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: It is not always possible to create linear access to the larynx using a rigid operating laryngoscope for microlaryngoscopy. In this study, we evaluate the usability of a novel curved surgical prototype with flexible instruments for the larynx (sMAC) in a simulation dummy and human body donor., Methods: In a user study (n = 6), head and neck surgeons as well as medical students tested the system for visualization quality and accessibility of laryngeal landmarks on an intubation dummy and human cadaver. A biopsy of the epiglottis was taken from the body donor. Photographic and time documentation was carried out., Results: The sMAC system demonstrated general feasibility for laryngeal surgery. Unlike conventional microlaryngoscopy, all landmarks could be visualized and manipulated in both setups. Biopsy removal was possible. Visibility of the surgical field remained largely unobstructed even with an endotracheal tube in place. Overall handling of the sMAC prototype was satisfactorily feasible at all times., Conclusion: The sMAC system could offer an alternative for patients, where microlaryngoscopy is not applicable. A clinical trial has to clarify if the system benefits in clinical routine.

The General Data Protection Regulation (GDPR) became binding law in the European Union Member States in 2018, as a step toward harmonizing personal data protection legislation in the European Union. The Regulation governs almost all types of personal data processing, hence, also, those pertaining to biomedical research. The purpose of this article is to highlight the main practical issues related to data and biological sample sharing that biomedical researchers face regularly, and to specify how these are addressed in the context of GDPR, after consulting with ethics/legal experts. We identify areas in which clarifications of the GDPR are needed, particularly those related to consent requirements by study participants. Amendments should target the following: (1) restricting exceptions based on national laws and increasing harmonization, (2) confirming the concept of broad consent, and (3) defining a roadmap for secondary use of data. These changes will be achieved by acknowledged learned societies in the field taking the lead in preparing a document giving guidance for the optimal interpretation of the GDPR, which will be finalized following a period of commenting by a broad multistakeholder audience. In parallel, promoting engagement and education of the public in the relevant issues (such as different consent types or residual risk for re-identification), on both local/national and international levels, is considered critical for advancement. We hope that this article will open this broad discussion involving all major stakeholders, toward optimizing the GDPR and allowing a harmonized transnational research approach.

Background: One of the main symptoms of severe infection with the new coronavirus‑2 (SARS-CoV-2) is hypoxemic respiratory failure because of viral pneumonia with the need for mechanical ventilation. Prolonged mechanical ventilation may require a tracheostomy, but the increased risk for contamination is a matter of considerable debate., Objective: Evaluation of safety and effects of surgical tracheostomy on ventilation parameters and outcome in patients with COVID-19., Study Design: Retrospective observational study between March 27 and May 18, 2020, in a single-center coronavirus disease-designated ICU at a tertiary care German hospital., Patients: Patients with COVID-19 were treated with open surgical tracheostomy due to severe hypoxemic respiratory failure requiring mechanical ventilation., Measurements: Clinical and ventilation data were obtained from medical records in a retrospective manner., Results: A total of 18 patients with confirmed SARS-CoV‑2 infection and surgical tracheostomy were analyzed. The age range was 42-87 years. All patients received open tracheostomy between 2-16 days after admission. Ventilation after tracheostomy was less invasive (reduction in PEAK and positive end-expiratory pressure [PEEP]) and lung compliance increased over time after tracheostomy. Also, sedative drugs could be reduced, and patients had a reduced need of norepinephrine to maintain hemodynamic stability. Six of 18 patients died. All surgical staff were equipped with N99-masks and facial shields or with powered air-purifying respirators (PAPR)., Conclusion: Our data suggest that open surgical tracheostomy can be performed without severe complications in patients with COVID-19. Tracheostomy may reduce invasiveness of mechanical ventilation and the need for sedative drugs and norepinehprine. Recommendations for personal protective equipment (PPE) for surgical staff should be followed when PPE is available to avoid contamination of the personnel.

Background. In the past few years, surgical robots have recently entered the medical field, particularly in urology, gynecology, and general surgery. However, the clinical effectiveness and safety of robot-assisted surgery (RAS) in the field of head and neck surgery has not been clearly established. In this review, we evaluate to what extent RAS can potentially be applied in head and neck surgery, in which fields it is already daily routine and what advantages can be seen in comparison to conventional surgery. Data sources. For this purpose, we conducted a systematic review of trials published between 2000 and 2021, as well as currently ongoing trials registered in clinicaltrials.gov. The results were structured according to anatomical regions, for the topics "Costs," "current clinical trials," and "robotic research" we added separate sections for the sake of clarity. Results. Our findings show a lack of large-scale systematic randomized trials on the use of robots in head and neck surgery. Most studies include small case series or lack a control arm which enables a comparison with established standard procedures. Conclusion. The question of financial reimbursement is still not answered and the systems on the market still require some specific improvements for the use in head and neck surgery.

Robot-assisted surgery (RAS) has already been approved for several clinical applications in head and neck surgery. In some Anglo-American regions, RAS is currently the common standard for treatment of oropharyngeal diseases. Systematic randomized studies comparing established surgical procedures with RAS in a large number of patients are unavailable so far. Experimental publications rather describe how to reach poorly accessible anatomical regions using RAS, or represent feasibility studies on the use of transoral robotic surgery (TORS) in established surgical operations. With general application of RAS in clinical practice, the question of financial reimbursement arises. Furthermore, the technical applications currently on the market still require some specific improvements for routine use in head and neck surgery.

Achilles tendon ruptures are very common tendon ruptures and their incidence is increasing in modern society, resulting in work incapacity and months off sport, which generate a need for accelerated and successful therapeutic repair strategy. Platelet-rich plasma (PRP) is emerging as adjuvant human blood-derived constructs to assist Achilles tendon rupture treatment. However, myriad PRP preparation methods in conjunction with poor standardization in the modalities of their applications impinge on the consistent effectiveness of clinical and structural outcomes regarding their therapeutic efficacy. The purpose of this review is to provide some light on the application of PRP for Achilles tendon ruptures. PRP has many characteristics that make it an attractive treatment. Elements such as the inclusion of leukocytes and erythrocytes within PRP, the absence of activation and activation ex vivo or in vivo, the modality of application, and the adjustment of PRP pH can influence the biology of the applied product and result in misleading therapeutic conclusions. The weakest points in demonstrating their consistent effectiveness are primarily the result of myriad PRP preparation methods and the poor standardization of modalities for their application. Selecting the right biological scaffold and applying it correctly to restitutio ad integrum of ruptured Achilles tendons remains a daunting and complex task.

Background: Distal nasolacrimal duct stenosis is usually treated by head and neck surgeons with transnasal endoscopic dacryocystorhinostomy (DCR). The presented clinical study discusses advantages and drawbacks of a robot-assisted endoscope positioning system, which allows for hands-free visualization of the surgical field., Material and Methods: Two patients were treated by surgical DCR. The endoscopic positioning system (Medineering ® ) features a mechatronic holding arm with four segments and seven degrees of freedom. It is driven by using a foot pedal., Results: Visualization and instrumentation of the surgical field including the relevant anatomical landmarks were feasible. The endoscope position could be controlled with sufficient precision. The surgeon was able to maintain bimanual instrumentation., Conclusion: The endoscope positioning system allows for two-handed surgery, which facilitates the essential steps of the surgical procedure. If the benefit of the system is sufficient for the use in clinical routine, it has to be evaluated in repeated applications., (© 2020 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery published by John Wiley & Sons Ltd.)

The interactions of dietary carotenoids, and particularly the xanthophylls in the macula, with singlet oxygen and three different oxy-radicals, (hydroxyl radical, nitrogen dioxide and the superoxide radical anion) are compared using pulsed laser and γ-techniques. The results give possible molecular mechanisms for the switch from anti-oxidant (protection) by carotenoids to pro-oxidant (damage) by carotenoids. The participation of oxygen in radical mechanisms in the presence of different carotenoids is compared for the different radicals. It is shown that the mechanistic role of oxygen differs very significantly for anti-/pro-oxidation by hydroxyl radicals when compared to nitrogen dioxide. Lutein was found to be an extremely good cell protector against hydroxyl radicals at all oxygen concentrations, including under physiological conditions.

Carotenoid pigments, particularly β-carotene and lycopene, are consumed in human foodstuffs and play a vital role in maintaining health. β-carotene is known to quench singlet oxygen and can have strong antioxidant activity. As such, it was proposed that β-carotene might reduce the risk of cancer. Epidemiological studies found inverse relationships between cancer risk and β-carotene intake or blood levels. However, clinical trials failed to support those findings and β-carotene supplementation actually increased lung cancer incidence in male smokers. Early experimental animal studies found dietary β-carotene inhibited UV-induced skin cancers. Later studies found that β-carotene supplementation exacerbated UV-carcinogenic expression. The discrepancies of these results were related to the type of diet the animals consumed. Lycopene has been associated with reduced risk of lethal stage prostate cancer. Other carotenoids, e.g., lutein and zeaxanthin, play a vital role in visual health. Numerous studies of molecular mechanisms to explain the carotenoids' mode of action have centered on singlet oxygen, as well as radical reactions. In cellular systems, singlet oxygen quenching by carotenoids has been reported but is more complex than in organic solvents. In dietary β-carotene supplement studies, damaging pro-oxidant reactivity can also arise. Reasons for this switch are likely due to the properties of the carotenoid radicals themselves. Understanding singlet oxygen reactions and the anti-/pro-oxidant roles of carotenoids are of importance to photosynthesis, vision and cancer.

The lymphocyte function-associated antigen 1 (LFA-1) is a member of the beta2-integrin family and plays a pivotal role for T cell activation and leukocyte trafficking under inflammatory conditions. Blocking LFA-1 has reduced or aggravated inflammation depending on the inflammation model. To investigate the effect of LFA-1 in myocarditis, mice with experimental autoimmune myocarditis (EAM) were treated with a function blocking anti-LFA-1 antibody from day 1 of disease until day 21, the peak of inflammation. Cardiac inflammation was evaluated by measuring infiltration of leukocytes into the inflamed cardiac tissue using histology and flow cytometry and was assessed by analysis of the heart weight/body weight ratio. LFA-1 antibody treatment severely enhanced leukocyte infiltration, in particular infiltration of CD11b+ monocytes, F4/80+ macrophages, CD4+ T cells, Ly6G+ neutrophils, and CD133+ progenitor cells at peak of inflammation which was accompanied by an increased heart weight/body weight ratio. Thus, blocking LFA-1 starting at the time of immunization severely aggravated acute cardiac inflammation in the EAM model.

Heart failure due to dilated cardiomyopathy is frequently caused by myocarditis. However, the pathogenesis of myocarditis remains incompletely understood. Here, we report the presence of neutrophil extracellular traps (NETs) in cardiac tissue of patients and mice with myocarditis. Inhibition of NET formation in experimental autoimmune myocarditis (EAM) of mice substantially reduces inflammation in the acute phase of the disease. Targeting the cytokine midkine (MK), which mediates NET formation in vitro, not only attenuates NET formation in vivo and the infiltration of polymorphonuclear neutrophils (PMNs) but also reduces fibrosis and preserves systolic function during EAM. Low-density lipoprotein receptor-related protein 1 (LRP1) acts as the functionally relevant receptor for MK-induced PMN recruitment as well as NET formation. In summary, NETosis substantially contributes to the pathogenesis of myocarditis and drives cardiac inflammation, probably via MK, which promotes PMN trafficking and NETosis. Thus, MK as well as NETs may represent novel therapeutic targets for the treatment of cardiac inflammation., (© 2019 Weckbach et al.)

Modern quantitative trait locus (QTL) studies in multiparental populations offer opportunities to identify causal genes for thousands of clinical and molecular traits. Traditional analyses examine each trait by itself. However, to fully leverage this vast number of measured traits, the systems genetics community needs statistical tools to analyze multiple traits simultaneously (Jiang & Zeng, 1995; Korol, Ronin, & Kirzhner, 1995). A test of pleiotropy vs. separate QTL is one such tool that will aid dissection of complex trait genetics and enhance understanding of genetic architecture.

Nanotechnology and, specifically, nanomedicine has been touted as the next breakthrough technology for medical sciences. Although there are large advances being seen in the preclinical phases of development, there is still a paucity of viable and effective nanomedicine technologies in the clinical setting. We attempt to provide some suggestions as to the stumbling blocks of meaningful translation of this technology from the bench to the bedside. We give due consideration to the role of evidence-based medicine, regulatory pathways, and the commercialization efforts of nanomedicine at various stages in playing key roles in moving this technology into clinical use.

Background: Mice lacking Foxp3+ regulatory T (Treg) cells develop severe tissue inflammation in lung, skin, and liver with premature death, whereas the intestine remains uninflamed. This study aims to demonstrate the importance of Foxp3+ Treg for the activation of T cells and the development of intestinal inflammation., Methods: Foxp3-GFP-DTR (human diphtheria toxin receptor) C57BL/6 mice allow elimination of Foxp3+ Treg by treatment with Dx (diphtheria toxin). The influence of Foxp3+ Treg on intestinal inflammation was tested using the CD4+ T-cell transfer colitis model in Rag-/- C57BL/6 mice and the acute DSS-colitis model., Results: Continuous depletion of Foxp3+ Treg in Foxp3-GFP-DTR mice led to dramatic weight loss and death of mice by day 28. After 10 days of depletion of Foxp3+ Treg, isolated CD4+ T-cells were activated and produced extensive amounts of IFN-γ, IL-13, and IL-17A. Transfer of total CD4+ T-cells isolated from Foxp3-GFP-DTR mice did not result in any changes of intestinal homeostasis in Rag-/- C57BL/6 mice. However, administration of DTx between days 14 and 18 after T-cell reconstitution, lead to elimination of Foxp3+ Treg and to immediate weight loss due to intestinal inflammation. This pro-inflammatory effect of Foxp3+ Treg depletion consecutively increased inflammatory cytokine production. Further, the depletion of Foxp3+ Treg from Foxp3-GFP-DTR mice increased the severity of acute dSS-colitis accompanied by 80% lethality of Treg-depleted mice. CD4+ effector T-cells from Foxp3+ Treg-depleted mice produced significantly more pro-inflammatory cytokines., Conclusion: Intermittent depletion of Foxp3+ Treg aggravates intestinal inflammatory responses demonstrating the importance of Foxp3+ Treg for the balance at the mucosal surface of the intestine.

Natural compounds which can behave as antioxidants and protect against UV-radiation may well have medical and cosmetic value. Usnic acid, which can be obtained from lichens offer such a potential. The latter is one of the best known and reviewed compounds present in lichens and exhibits many properties of value such as antibiotic, antitumor and UV-filter-effects. We report studies of the potential antioxidant and prooxidant activity of usnic acid extracted from Xanthoparmelia farinosa (Vainio) using a human lymphocyte cell line (Jurkat-cells) under UV-B-irradiation. Cell survival and cell metabolism were determined using different conditions such as usnic acid concentration and UVB dose. Compared to the controls the cells incubated with usnic acid in concentrations of 1 x 10(-8) and 1 x 10(-6) M showed a higher cell survival and a normal metabolism under low doses of UVB-light up to 0.1 J/cm(2). When both higher UVB doses (up to 14 J/cm(2)) and higher concentrations of usnic acid (1 x 10(-4) M) where used, the opposite effect was observed. It is concluded that these effects are due to bifunctional (a switch of) anti-oxidative-pro-oxidative behaviour of usnic acid under UV-B-irradiation., (Copyright 2010 Elsevier B.V. All rights reserved.)

Genome-wide scans of nucleotide variation in human subjects are providing an increasing number of replicated associations with complex disease traits. Most of the variants detected have small effects and, collectively, they account for a small fraction of the total genetic variance. Very large sample sizes are required to identify and validate findings. In this situation, even small sources of systematic or random error can cause spurious results or obscure real effects. The need for careful attention to data quality has been appreciated for some time in this field, and a number of strategies for quality control and quality assurance (QC/QA) have been developed. Here we extend these methods and describe a system of QC/QA for genotypic data in genome-wide association studies (GWAS). This system includes some new approaches that (1) combine analysis of allelic probe intensities and called genotypes to distinguish gender misidentification from sex chromosome aberrations, (2) detect autosomal chromosome aberrations that may affect genotype calling accuracy, (3) infer DNA sample quality from relatedness and allelic intensities, (4) use duplicate concordance to infer SNP quality, (5) detect genotyping artifacts from dependence of Hardy-Weinberg equilibrium test P-values on allelic frequency, and (6) demonstrate sensitivity of principal components analysis to SNP selection. The methods are illustrated with examples from the "Gene Environment Association Studies" (GENEVA) program. The results suggest several recommendations for QC/QA in the design and execution of GWAS., ((c) 2010 Wiley-Liss, Inc.)

Aims: The goals of this study were to (1) estimate the prevalence of HIV infection among women accessing services at a women's health center in rural Haiti and (2) to identify economic risk factors for HIV infection in this population., Methods: Women who accessed healthcare services at this center between June 1999 and December 2002 were recruited to participate. The analysis was based on data from a case-control study of sexually transmitted diseases (STDs) in rural Haiti. HIV prevalence in the study population was 4%., Results: In multivariate analyses, partner occupation was associated with HIV infection in women, with mechanic (OR 9.0, 95% CI 1.8-45) and market vendor (OR 4.2, 95% CI 1.6-11) reflecting the strongest partner occupational risk factors. Partner's occupation as a farmer reduced the risk of infection in women by 60% (95% CI 0.14-1.1). Factors indicating low socioeconomic status (SES), such as food insecurity (OR 2.0, 95% CI 0.75-5.6) and using charcoal for cooking (OR 1.7, 95% CI 0.72-3.8) suggested an association with HIV infection., Conclusions: Given pervasive gender inequality in Haiti, women's economic security often relies on their partners' income earning activities. Our findings show that although factors reflecting poverty are associated with HIV-positive status, stronger associations are observed for women whose partners indicated a more secure occupation (e.g., mechanic or market vendor). Policies and programs that expand access to education and economic opportunities for women and girls may have long-term implications for HIV prevention in Haiti and other resource-poor settings.

We explored the utility of population- and pedigree-based analyses using the Framingham Heart Study genome-wide 50 k single-nucleotide polymorphism marker data provided for Genetic Analysis Workshop 16. Our aims were: 1) to compare identity-by-descent sharing estimates from variable amounts of data; 2) to apply each of these estimates to a case-control association study designed to control for relatedness among samples; and 3) to contrast these results to those obtained using model-based and model-free linkage analysis methods.

Fundamental photophysical properties have been obtained for six polyaromatics, calycine, usnic acid, vicanicine, 1-Cl-pannerine and epiphorelic acids I and II, extracted from Antarctic lichens--potential future sunscreens. None of the lichen compounds produced a measurable amount of triplet states and the singlet oxygen quantum yield was also very low ranging from 0.003 to 0.06. However, three exhibited triplet energy levels which may be above that of thymine. The radical cations of calycine and usnic acid were generated via pulse radiolysis and were observed to be quenched by vitamin C, vitamin E and Trolox.

Natural substances extracted from lichens and boldo tree were tested in vivo and in vitro as possible UV-light filters. The protection factors were compared with that found for the references: Nivea sun Spray LSF 5, octylmethoxycinnamate (OMC) and 4-tert.-butyl-4'-methoxy dibenzoylmethane (BM-DBM). The stability of the single compounds was studied through UV-Vis spectroscopy. Usnic acid resulted to be the best UVB filter, with an in vivo protection factor similar to Nivea sun Spray LSF 5. Most of the single compounds studied in vitro resulted to have higher or similar filtering power than octylmethoxycinnamate. The protection factors as well as the good UV-light absorption of their photo-products suggest that these natural substances may be useful as new filters in sun-screen preparations.

The cytotoxic and photocytotoxic effects of two water-soluble fullerene derivatives, a dendritic C(60) mono-adduct and the malonic acid C(60) tris-adduct were tested on Jurkat cells. Cell growth and vitality were determined by a cell counting and staining technique. After 2 weeks cultivation in the presence of the fullerene derivatives, it was found that only the dendritic mono-adduct inhibits cell growth (within 2 weeks the cell number decreased to 19%), whereas the tris-malonic acid adduct has little effect. The growth inhibition is reversible; cultivating the same cells further in the absence of fullerene, the cell number increased to 106.4%. Other experiments showed that these fullerene derivatives become toxic when irradiated with UVA or UVB light. The cell death is mainly caused by membrane damage and it is UV dose-dependent. Tris-malonic acid fullerene was found to be more phototoxic than the dendritic derivative. This result is in contrast to the singlet oxygen quantum yields determined for the two compounds. We propose that the two fullerene derivatives may interact with the cell membrane in different ways thus causing the observed effects. Further experiments will be done to determine the location and concentration of the two compounds in and on the cells.

Objective: Recent developments permit the use of pulse oximetry to evaluate fetal oxygenation in labor. We tested the hypothesis that the addition of fetal pulse oximetry in the evaluation of abnormal fetal heart rate patterns in labor improves the accuracy of fetal assessment and allows safe reduction of cesarean deliveries performed because of nonreassuring fetal status., Study Design: A randomized, controlled trial was conducted concurrently in 9 centers. The patients had term pregnancies and were in active labor when abnormal fetal heart rate patterns developed. The patients were randomized to electronic fetal heart rate monitoring alone (control group) or to the combination of electronic fetal monitoring and continuous fetal pulse oximetry (study group). The primary outcome was a reduction in cesarean deliveries for nonreassuring fetal status as a measure of improved accuracy of assessment of fetal oxygenation., Results: A total of 1010 patients were randomized, 502 to the control group and 508 to the study group. There was a reduction of >50% in the number of cesarean deliveries performed because of nonreassuring fetal status in the study group (study, 4. 5%; vs. control, 10.2%; P =.007). However, there was no net difference in overall cesarean delivery rates (study, n = 147 [29%]; vs. control, 130 [26%]; P = .49) because of an increase in cesarean deliveries performed because of dystocia in the study group. In a blinded partogram analysis 89% of the study patients and 91% of the control patients who had a cesarean delivery because of dystocia met defined criteria for actual dystocia. There was no difference between the 2 groups in adverse maternal or neonatal outcomes. In terms of the operative intervention for nonreassuring fetal status, there was an improvement in both the sensitivity and the specificity for the study group compared with the control group for the end points of metabolic acidosis and need for resuscitation., Conclusion: The study confirmed its primary hypothesis of a safe reduction in cesarean deliveries performed because of nonreassuring fetal status. However, the addition of fetal pulse oximetry did not result in an overall reduction in cesarean deliveries. The increase in cesarean deliveries because of dystocia in the study group did appear to result from a well-documented arrest of labor. Fetal pulse oximetry improved the obstetrician's ability to more appropriately intervene by cesarean or operative vaginal delivery for fetuses who were actually depressed and acidotic. The unexpected increase in operative delivery for dystocia in the study group is of concern and remains to be explained.

We report on the initial results from a measurement of the antineutrino flux and spectrum at a distance of about 800 m from the three reactors of the Palo Verde Nuclear Generating Station using a segmented gadolinium-loaded scintillation detector. We find that the antineutrino flux agrees with that predicted in the absence of oscillations excluding at 90% C.L. nu;(e)-nu;(x) oscillations with Deltam(2)>1.12x10(-3) eV(2) for maximal mixing and sin (2)2straight theta>0.21 for large Deltam(2). Our results support the conclusion that the atmospheric neutrino oscillations observed by Super-Kamiokande do not involve nu(e).

Objective: To compare endoscopic coverage of myelomeningocele with a maternal split-thickness skin graft in utero to definitive neurosurgical closure through a hysterotomy., Methods: Four fetuses with isolated myelomeningocele underwent endoscopic coverage of the defect with a maternal split-thickness skin graft in a CO(2) environment at 22-24 weeks' gestation. Subsequently, 4 fetuses underwent standard neurosurgical closure of their myelomeningoceles at 28-29 weeks' gestation., Results: The mean operating time for the endoscopic procedures was 297 +/- 69 min. Two fetal losses occurred as a result of chorioamnionitis and placental abruption, respectively. A third baby delivered at 28 weeks' gestation after prolonged disruption of the membranes. The 2 survivors required standard closure of the myelomeningocele after delivery. The mean operating time for the hysterotomy procedures was 125 +/- 8 min. No mortality occurred, and all the infants delivered between 33 and 36 weeks with well-healed myelomeningocele scars. At present, the functional levels of all infants approximate the anatomical levels of the lesions., Conclusion: With current technology, in utero repair of congenital myelomeningocele through a hysterotomy appears to be technically superior to procedures performed endoscopically., (Copyright 2000 S. Karger AG, Basel.)

Objective: The purpose of this study was to test the ability of a clearly defined classification system for electronic fetal heart rate monitoring to predict early neonatal outcome., Study Design: All labors of women with singleton pregnancies > or = 32 weeks' gestation electronically monitored at 2 institutions were examined. Tracings in the final hour before delivery were defined as normal, fetal stress, or fetal distress. After delivery, Apgar scores, cord blood gas values, and admission to the neonatal intensive care unit were examined as measures of early neonatal outcome., Results: Among the 898 patients who qualified for study, 627 (70%) had tracings classified as normal, 263 (29%) had tracings classified as fetal stress, and 8 (1%) had tracings classified as fetal distress. There was a significant worsening of neonatal outcome across these 3 groups with regard to depressed Apgar scores 1 minute (5.1%, 18.3%, and 75.0%; P <.05), depressed Apgar scores at 5 minutes (1.0%, 3.8%, and 37.5%; P <.05), and admission to the neonatal intensive care unit (5.6%, 10.6%, and 37.5%; P <.05). There was also a progressive worsening of cord blood pH (7.27 +/- 0.06, 7.21 +/- 0.08, and 7.06 +/- 0.14; P <.05), a progressive increase in PCO (2) (53.39 +/- 8.34 mm Hg, 58.51 +/- 10.55 mm Hg, and 78.31 +/- 20.35 mm Hg; P <.05), and a progressive decline in base excess (-3.18 +/- 2.02 mEq/L, -5. 11 +/- 3.11 mEq/L, and -9.07 +/- 4.59 mEq/L; P <.05)., Conclusion: This simple classification system for interpreting fetal heart rate tracings accurately predicts normal outcomes for fetuses as well discriminating fetuses in true distress. Further, it identifies an intermediate group of fetuses with a condition labeled fetal stress who might benefit from additional evaluation and possibly from expeditious delivery.

The most serious consequence for patients following laryngectomy is the restriction of verbal communication. Since the introduction of laryngectomy significant concerns have already been focused on the field of speech rehabilitation. The operational procedures for the speech rehabilitation include training of the oesophageal voice speech and the voice prostheses. Speech prostheses are available in our hospital since 1983. The speech quality of the speech prostheses is compared with the classical oesophageal voice or to the voice by means of a Provox speech help. Bacteriological and mycological colonisation as a function of the length of implantation are defined. Our approach to the voice rehabilitation after a laryngectomy by use of a spacer during the laryngectomy has proven successful. As a result patients do not fall into a "hole" of non verbal communication. The aim of our efforts is always to create a functioning oesophageal voice after leaving the care of the hospital.

Intrapartum fetal heart rate monitoring is commonly used to evaluate fetal status in labor, despite a lack of convincing randomized studies to support its use. The National Institutes of Health have helped standardize fetal heart rate monitoring terminology with their 1997 task force report, which will aid clinicians and scientists in their goal of providing quality care and research. The American College of Obstetricians and Gynecologists has recommended the term nonreassuring fetal status for electronic fetal monitor patterns that are not normal; however, Vanderbilt continues to use the terms fetal stress and fetal distress, using specific criteria for each. The approximately 30% of fetal heart rate tracings labeled as fetal stress (or nonreassuring fetal status) can be evaluated further by the use of fetal pulse oximetry, a new technology currently under evaluation in this country.

Context: Intrauterine closure of exposed spinal cord tissue prevents secondary neurologic injury in animals with a surgically created spinal defect; however, whether in utero repair of myelomeningocele improves neurologic outcome in infants with spina bifida is not known., Objective: To determine whether intrauterine repair of myelomeningocele improves patient outcomes compared with standard care., Design: Single-institution, nonrandomized observational study conducted between January 1990 and February 1999., Setting: Tertiary care medical center., Participants: A sample of 29 study patients with isolated fetal myelomeningocele referred for intrauterine repair that was performed between 24 and 30 gestational weeks and 23 controls matched to cases for diagnosis, level of lesion, practice parameters, and calendar time. All infants were followed up for a minimum of 6 months after delivery., Main Outcome Measures: Requirement for ventriculoperitoneal shunt placement, obstetrical complications, gestational age at delivery, and birth weight for study vs control subjects., Results: The requirement for ventriculoperitoneal shunt placement for decompression of hydrocephalus was significantly decreased among study infants (59% vs 91%; P = .01). The median age at shunt placement was also older among study infants (50 vs 5 days; P = .006). This may be explained by the reduced incidence of hindbrain herniation among study infants (38% vs 95%; P<.001). Following hysterotomy, study patients had an increased risk of oligohydramnios (48% vs 4%; P = .001) and admission to the hospital for preterm uterine contractions (50% vs 9%; P = .002). The estimated gestational age at delivery was earlier for study patients (33.2 vs 37.0 weeks; P<.001), and the birth weight of study neonates was less (2171 vs 3075 g; P<.001)., Conclusions: Our study suggests that intrauterine repair of myelomeningocele decreases the incidence of hindbrain herniation and shunt-dependent hydrocephalus in infants with spina bifida, but increases the incidence of premature delivery.

Objective: Our goal was to compare the use of a specially designed trocar for initial uterine entry with standard entry by electrocautery in creation of a hysterotomy for fetal surgery., Study Design: Ten consecutive patients undergoing hysterotomy for intrauterine repair of myelomeningocele were randomized to initial uterine entry with electrocautery or with the Tulipan-Bruner trocar. Timing of initial uterine entry with electrocautery began with incision into the uterine serosa and ended with incision of the chorioamnionic membranes. Timing of initial uterine entry with the Tulipan-Bruner trocar began with placement of stay sutures and ended with removal of the central introducer from the peel-away sheath. Blood loss was estimated by the primary surgeon. All of the participating surgeons judged the convenience and ease of each technique. The times required for initial uterine entry were compared with an unpaired t test. Statistical significance was set at P <.05., Results: The time required for initial uterine entry with electrocautery was 231 +/- 63 (mean +/- SD) seconds compared with 146 +/- 51 seconds with the trocar (P <.05). The total blood loss for all 10 cases was <50 mL, but the presence of blood in the wound was judged much more inconvenient when electrocautery was used. Finally, electrocautery required 2 surgical assistants in every case, whereas the trocar was readily placed with only a single assistant., Conclusion: The Tulipan-Bruner trocar provides quicker, less traumatic uterine entry during creation of a hysterotomy, as compared with electrocautery.

Sinusoidal fetal heart rate may have a spectrum of occurrence that indicates degree of fetal morbidity. Twelve cases of intermittent sinusoidal fetal heart rate were reviewed for fetal outcome. Findings of anemia, low umbilical cord pH, and large base excess support that intermittent sinusoidal fetal heart rate may be an early indicator of impending fetal compromise.

Objective: To compare the effectiveness of routine management of patients at high risk for preterm delivery to the effectiveness of routine management in combination with daily telephone nursing contact., Study Design: The control group, 1 (n = 21), had education and frequent prenatal visits and cervical examinations. The study group, 2 (n = 21), had education, frequent prenatal visits and cervical examination, and daily telephone contact. Group 3 (n = 22) received education but refused to participate., Results: There were no significant differences (SD) between groups in race, smoking, age, multiple gestation, visits, diagnosis of premature labor, mean days gained after diagnosis of premature labor, tocolytic use or bed rest. There was also no SD in preterm birth rate, mode of delivery, number of maternal or neonatal hospital days, mean neonatal weight or gestational age at delivery between groups. While not reducing the overall incidence of preterm birth, this management for all groups resulted in a more advanced gestational age at the time of delivery (mean change = 7.5 weeks, P < .0001) when compared to the patient's first preterm birth., Conclusion: This study indicated that daily contact, while providing reassurance and support, did not change the outcome when the study group was compared to women managed similarly but without daily contact.

Background: Placenta previa incerta, although uncommon, assumes considerable clinical significance because of the morbidity associated with severe hemorrhage, uterine perforation and infection. The majority of cases are unanticipated and initially identified intraoperatively., Case: Placenta accreta was diagnosed sonographically at 18 weeks' gestation in a multipara who had previously undergone cesarean delivery. Additionally, the gestation was complicated by chronic renal failure secondary to systemic lupus erythematosus. After appropriate counseling, total abdominal hysterectomy was performed prior to fetal viability., Conclusion: Early sonographic evaluation of the placenta is recommended for those at significant risk of invasive placentation. Timely detection facilitates proper preparation and should reduce maternal morbidity.

The clinical use of intrapartum fetal heart rate monitoring remains controversial. Because of its widespread use in this country, interpretation skills must be maintained. Clear and concise criteria for the diagnosis of fetal stress and distress are presented in this article, and the management of fetal distress is discussed.

The umbilical artery Doppler ultrasonographic gradient has been described, and the need for site-specific nomograms has been pointed out. However, controversy still exists about the cause of this phenomenon and the optimal site for obtaining umbilical artery Doppler ultrasonographic measurements. Cross-sectional measurements of umbilical artery flow velocity waveform (FVW) systolic/diastolic (S/D) ratios were therefore made in 35 gravid women during the second or third trimester of pregnancy with both duplex pulsed-wave (PW) and free-standing continuous-wave (CW) Doppler ultrasonographic equipment. Multiple duplex PW Doppler ultrasonographic signals were recorded at the abdominal cord insertion, placental cord insertion, and free cord sites. Multiple CW Doppler FVWs were obtained from four quadrants, in decreasing order of ease of measurement. Repeated-measures analysis of variance demonstrated a statistically significant decrease in mean and median values of the umbilical artery S/D ratio from the abdominal cord insertion site to the placental cord insertion site. The reduction in the value of the S/D ratio as the placental cord insertion site is approached results more from a decrease in the peak systolic maximum velocity envelope than from an increase in diastolic velocities. Moreover, mean and median CW Doppler ultrasonographic values correlate most closely with corresponding PW measurements of the free cord segment. These data confirm the presence of the umbilical artery Doppler ultrasonographic gradient. Decreasing values of the S/D ratio from the fetal abdomen to the placenta are a result of attenuation of the systolic maximum velocity envelope.(ABSTRACT TRUNCATED AT 250 WORDS)

The neuroprotective actions of the anticonvulsant phenytoin (diphenylhydantoin, PHT) were evaluated using 3 week old primary hippocampal cultures derived from 19 day embryonic rat. When added to the culture medium prior to a hypoxic insult, PHT increased neuronal viability two-fold. Doubling extracellular Mg2+ concentration was similarly neuroprotective. In contrast, PHT was unable to protect against hypoxia-induced death in one week old cultures, nor was PHT protective against N-methyl-D-aspartate (NMDA)-induced neurotoxicity in cultures of either age. These findings suggest that non-NMDA receptor mechanisms are important in hypoxia-induced neuronal death, and may have important implications for the treatment of stroke.

Objective: Our purpose was to correlate measures of Doppler-detected fetal movements with standard fetal heart rate parameters and perinatal outcomes., Study Design: This prospective, multiinstitutional trial used the Hewlett-Packard M1350A monitor to record simultaneous fetal heart rate baseline, variability, accelerations, decelerations, and number of fetal movements, and duration and percent of total time. These data were compared at 10- and 30-minute intervals during nonstress tests and were correlated with fetal heart rate baseline parameters and maternally perceived fetal movements and with outcomes of infants delivered within 7 days of the last test., Results: At six centers 1704 actocardiograms from 884 third-trimester patients were analyzed. Doppler-detected fetal movement counts, durations, and percent of total time correlated weakly with all baseline fetal heart rate parameters (all values < 0.20). All fetal movement parameters increased significantly in successive 10-minute blocks and in periods of increased or normal fetal heart rate variability compared with those with fetal heart rate variability. The sensitivity, specificity, and predictive values of the percent of total movement time were comparable to those of standard nonstress test parameters. The risk of poor perinatal outcomes after nonreactive nonstress tests was lower in cases with fetal movements than in those without., Conclusions: Doppler actocardiography may help to discriminate fetal states during antepartum testing. It may prevent inappropriate diagnosis of fetal compromise when the nonstress test is nonreactive or nonreassuring.

Electrical stimulation of the S2 nerve root can be used to produce detrusor contraction and voiding in patients with spinal cord injury, but concurrent stimulation of the external urethral sphincter causes detrusor-sphincter dyssynergia. This has been managed with a second surgical procedure, peripheral transection of the pudendal nerve. In this study, performed in dogs after spinal cord transection, laminectomy and ventral foraminotomy permitted tracing of the S2 root into the pelvis, where its branches were identified by electrical stimulation and urodynamic recording. The pudendal (somatic) branch was sectioned; the autonomic branch innervating the detrusor was preserved. Electrical stimulation of the proximal S2 root then produced detrusor contraction without contraction of the external urethral sphincter. This approach, which requires a single operation and spares pudendal nerve functions mediated by nerve roots other than S2, may enable a neurostimulator to provide effective voiding, without detrusor-external sphincter dyssynergia, in man.

Objective: Our purpose was to describe Vanderbilt University Medical Center's experience in establishing a chorionic villus sampling program and the importance of quality control along with a continuous improvement model on the first 1000 cases., Study Design: A continuous improvement model was established with emphasis on a multidisciplinary team approach and quality assurance process. A computerized data base was used for continuing analysis of complications and for allowing facile access to pertinent information., Results: A continuous improvement model allowed for an improved process and outcome for patients, personnel, and referring health care providers. Follow-up for initial symptoms after chorionic villus sampling was obtained on 98.5% of patients. Pregnancy follow-up, including birth data, was obtained on 93%., Conclusion: A continuous improvement mode from the project's onset resulted in an improved process and outcome, information helpful for accessing spontaneous abortion rates and pregnancy outcomes (including the incidence of limb abnormalities and factors associated with abortions) and recommendations for training personnel.

A new approach to the basilar apex in a patient with a megadolichobasilar anomaly and an abnormally rostral basilar apex aneurysm is described. The details of the surgical approach and the advantages and limitations of this transcallosal, interseptal approach are described.