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Biomedical subjects

K Roth

Publications and source records attributed to K Roth.

At least 19 recordsLinked to original sources

Interferometric coupling of the Keck telescopes with single-mode fibers.

Here we report successful interferometric coupling of two large telescopes with single-mode fibers. Interference fringes were obtained in the 2- to 2.3-micrometer wavelength range on the star 107 Herculis by using the two Keck 10-meter telescopes, each feeding their common interferometric focus with 300 meters of single-mode fibers. This experiment demonstrates the potential of fibers for future kilometric arrays of telescopes and is the first step toward the 'OHANA (Optical Hawaiian Array for Nanoradian Astronomy) interferometer at the Mauna Kea observatory in Hawaii. It opens the way to sensitive optical imagers with resolutions below 1 milli-arc second. Our experimental setup can be directly extended to large telescopes separated by many hundreds of meters.

Journal Article↗

The afterglow of GRB 050709 and the nature of the short-hard gamma-ray bursts.

The final chapter in the long-standing mystery of the gamma-ray bursts (GRBs) centres on the origin of the short-hard class of bursts, which are suspected on theoretical grounds to result from the coalescence of neutron-star or black-hole binary systems. Numerous searches for the afterglows of short-hard bursts have been made, galvanized by the revolution in our understanding of long-duration GRBs that followed the discovery in 1997 of their broadband (X-ray, optical and radio) afterglow emission. Here we present the discovery of the X-ray afterglow of a short-hard burst, GRB 050709, whose accurate position allows us to associate it unambiguously with a star-forming galaxy at redshift z = 0.160, and whose optical lightcurve definitively excludes a supernova association. Together with results from three other recent short-hard bursts, this suggests that short-hard bursts release much less energy than the long-duration GRBs. Models requiring young stellar populations, such as magnetars and collapsars, are ruled out, while coalescing degenerate binaries remain the most promising progenitor candidates.

Journal Article↗

[Ovarian torsion in childhood].

A six year old afebrile girl was referred to the emergency department with abdominal pain in the right lower region. A retrouterine partially cystic lesion with an inhomogene echogenity was demonstrated by transabdominal ultrasound. Pelvic MR showed an enlarged right-sided ovary and a thickened vascular pedicle as well as few adjacent free fluid. Diagnosis of ovarian torsion was confirmed intraoperatively. Conservative ovary-sparing treatment was not possible, so right-sided adnexectomy followed. Histopathologically a haemorrhagic infarction of the ovary and the tube was seen. No signs of malignancy and no tumor could be detected.

Abdomen, Acute↗

Off-label use of proton pump inhibitors and P-blockers in general practices: an analysis using the Disease Analyzer--mediplus patient database.

OBJECTIVE: The off-label use of medicines is a widespread phenomenon in medical practice but discussion on the legality of using drugs outside their licensed indications is still ongoing. Prescription recommendations and prescribing habits can differ greatly. We have used a database tool to analyze replies to a batch of questions which included the question "Is the off-label use of medications common?". The analysis was carried out using the Disease Analyzer--mediplus patient database, which is a database tool registered in Germany. It enabled the anonymous access to a representative panel of physicians and patients. More than 1,500 medical practices representing approximately 2.5 million patients were analyzed in a cross-sectional or longitudinal manner. The Disease Analyzer--mediplus database is unique in that it has direct links to individual diagnoses and the corresponding therapy. RESULTS: The findings demonstrated that proton pump inhibitors (PPI), which are licensed for the treatment of gastric ulcer and gastric reflux, are also used off-label in gastritis. The off-label use varies from 30 - 40% of prescriptions. The data indicate that the prescribing behavior has been influenced by the ending of the patent protection on omeprazole. A second instance which has been identified involves the beta-blocker carvedilol, which is licensed for the treatment of heart failure (24% of the total number of patients receiving the drug) but it was found that other beta-blockers are used off-label in this indication at a rate of more than 10% of prescriptions. CONCLUSION: The off-label use of drugs is high, especially in gastritis and heart failure. The investigation has also confirmed that the Disease Analyzer--mediplus database provides quantitative and qualitative analyses combining all relevant information concerning physicians, patients, diagnoses and therapy and that this information can be used to evaluate prescribing habits and trends with regard to the off-label use of drugs.

Adolescent↗

Specific hygiene issues relating to reprocessing and reuse of single-use devices for laparoscopic surgery.

OBJECTIVE: To determine whether reprocessed single-use devices (SUD) would (1) meet regulatory standards for sterility, and (2) meet the same material standards as new devices or if they pose an infection risk to other patients. DESIGN: The study included in the first stage single-use laparoscopic dissection devices and in the second stage a variety of clinically used and reprocessed SUDs. The suitability of these devices for cleaning, disinfection, and sterilization was examined. METHODS: Testing of cleanability was conducted on devices contaminated with radioactively labeled blood. Instruments were cleaned using hospital recommended practices. Gamma counts/second were determined before and after cleaning to localize contaminants, which were additionally visualized using light and scanning electron microscopy (SEM). X-ray photoelectron spectroscopy (XPS) was used to quantify contamination elements on the materials tested. Residual bioburden testing on instruments contaminated with microorganisms suspended in blood prior to reprocessing was carried out to establish the efficacy of disinfection and sterilization. RESULTS: During the first stage of the study all devices remained contaminated after cleaning, but were effectively disinfected. Sterilization could not eliminate the challenge microorganisms completely. The findings during the second stage--examination of clinically used devices--were as follows: 11% of the sterile packages were damaged; 33% of the devices were incomplete and parts were missing; 54% did not meet the criteria for functionality; light microscopy, SEM, and XPS showed contamination on the outside and inside of all devices. Of the tested SUDs, 40% remained unsterile following resterilization. CONCLUSIONS: None of the reprocessed SUDs were effectively cleaned or sterilized. This may provide an opportunity for survival and growth of non-resistant or nosocomial organisms and viruses. The use of such inadequately reprocessed SUDs increases the risk for the patient, and can lead to nosocomial infection and to legal consequences for the health care facility.

Blood↗

Decontaminated single-use devices: an oxymoron that may be placing patients at risk for cross-contamination.

OBJECTIVE: To determine whether reprocessed single-use devices would meet regulatory standards for sterility and meet the same materials standards as a new device. DESIGN: The study included single-use and reusable biopsy forceps and papillotomes and a reusable stone retrieval basket. The suitability of these devices for cleaning and disinfection or sterilization was examined. METHODS: Testing of cleanability was conducted on devices contaminated with technetium 99-radiolabeled human blood. Instruments were cleaned using hospital recommended practices for manual cleaning. Gamma counts per second were determined before and after cleaning to localize contaminants, which were additionally visualized using light and scanning electron microscopy. X-ray photoelectron spectroscopy was used to quantify contamination elements on the materials tested. Residual bioburden testing on instruments contaminated with microorganisms suspended in coagulable sheep blood was carried out to establish the efficacy of disinfection and sterilization. RESULTS: All devices remained contaminated after cleaning, but single-use devices and the stone basket tended to be more heavily contaminated than reusable forceps and papillotomes. Cleaning procedures facilitated distribution of contaminants further into the lumens of the disposable forceps. Decreased concentrations of silicon and increased concentrations of carbon and nitrogen suggested that layers of silicon lubricant had been removed and contaminants were organic material. Reusable devices were effectively disinfected, but single-use devices were not. Sterilization could not eliminate the challenge microorganisms completely. CONCLUSIONS: None of the reprocessed single-use instruments were effectively cleaned, disinfected, or sterilized. This condition may provide an opportunity for the viability of nonresistant or nosocomial organisms and viruses. Additionally, reprocessing procedures may result in material destruction of fragile devices. Cost-saving initiatives that have inspired reprocessing of single-use devices, despite the absence of data establishing the efficacy of decontamination and the durability of materials throughout reprocessing, should be pushed into the background.

Blood-Borne Pathogens↗

Mcl-1 deficiency results in peri-implantation embryonic lethality.

We disrupted the Mcl-1 locus in murine ES cells to determine the developmental roles of this Bcl-2 family member. Deletion of Mcl-1 resulted in peri-implantation embryonic lethality. Mcl-1(-/-) embryos do not implant in utero, but could be recovered at E3.5-4.0. Null blastocysts failed to hatch or attach in vitro, indicating a trophectoderm defect, although the inner cell mass could grow in culture. Of note, Mcl-1(-/-) blastocysts showed no evidence of increased apoptosis, but exhibited a delay in maturation beyond the precompaction stage. This model indicates that Mcl-1 is essential for preimplantation development and implantation, and suggests that it has a function beyond regulating apoptosis.

Animals↗

Telepathology by the Internet.

A new concept for telemicroscopy has recently been introduced using the Internet and conventional web browser, with Java support for microscope remote control as well as image transfer and discussion (http://amba.charite.de/telemic/). The system has two major components: the telemicroscopy server, which is a computer with Internet access connected to the automatic microscope, and the telemicroscopy client, who remotely operates the microscope. This simplified telemicroscopy system allows any Internet user to become a consultant for telepathology without the acquisition of specialized hardware or software. For the inquirer seeking advice, however, this solution is still very expensive, since it requires a fully automated microscope. The present study describes a system that can be used for conventional microscopes. A video camera mounted on a microscope with a photo tube is connected to the frame grabber of a PC. Java-based telemicroscopy software transforms the computer into an Internet server, which automatically distributes new microscope images, after manual operations, to all connected clients. Any Internet user can access the web page of the server to become a telemicroscopy client. A Chat function allows for the online exchange of written text and a Discuss function enables the mouse button to display an arrow to all connected clients, which highlights distinct structures of the images. The system was optimized for simplicity, while presenting all features that are necessary to show and discuss difficult cases with any expert in the field who has Internet access. It offers new perspectives for telepathology and it is envisaged that many pathologists and scientists will use this facility to connect their personal microscopes to the Internet, forming a network for teleconsultation. To foster this development, the software described in this paper is being made freely available. Hopefully, this development will promote communication between pathologists and may thus increase the quality of diagnosis. Information on inquiry and installation of the software is available at the website mentioned above. Telemicroscopy sessions using the Telemic version for conventional microscopes can be scheduled by contacting the authors by e-mail (iver. petersen@charite.de).

Communication↗

The Tübingen balloon. A new method for adjusting the tension of the fundic wrap during laparoscopic Nissen fundoplication.

An adequate fundic wrap is fundamental to the success of conventional and laparoscopic Nissen fundoplications. Nevertheless, up to now there has been no standardized method for the surgeon to determine intraoperatively the width and tension of the fundic wrap according to objective criteria. With the support of Rüsch (Kernen, Germany), we developed a measurement balloon for use in laparoscopic Nissen fundoplication. The balloon allows the surgeon to define the width of the wrap and predetermine its length, as well as to measure its tension. Depending on the measured balloon pressure, the surgeon can perform fundic sutures more or less tightly. On the basis of 41 fundoplication model tests, we found that a fundic wrap typically described as "loose and floppy" produced a balloon pressure of 50-60 mmHg. In 10 laparoscopic Nissen fundoplications on domestic pigs, we were able to adjust the fundic wrap intraoperatively to a balloon pressure in this range (mean; 53.5; SD; 2.25). After the optimal intraoperative balloon pressure in humans has been investigated in a prospective study that is in progress, the Tübingen balloon is expected to serve as an instrument for quality assurance in reflux surgery.

Animals↗

The effect of nutritional supplementation on survival in seriously ill hospitalized adults: an evaluation of the SUPPORT data. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

BACKGROUND: Enteral tube and parenteral hyperalimentation are widely used nutritional support systems. Few studies examine the relation between nutritional support and patient outcomes in seriously ill hospitalized adults. OBJECTIVE: To explore the association between nutritional support and survival in seriously ill patients enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). DESIGN: A prospective study of preferences, decision-making, and outcomes. SETTING: Five teaching hospitals PARTICIPANTS: 6298 patients aged 18 or older meeting diagnostic and illness severity criteria. MEASUREMENT: Demographic characteristics, diagnoses, comorbid conditions, acute physiology score, nutritional support, and functional status before hospitalization. RESULTS: A total of 2149 patients received nutritional support. In patients who received artificial nutrition on hospital days 1 or 3 (Cohort 1), enteral feeding was associated with improved survival in coma (hazard: 0.53; 95%CI, 0.42-0.66), and reduced survival in COPD (hazard: 1.57; 95%CI, 1.18-2.08). In patients who were hospitalized on Day 7 and received artificial nutrition on days 1, 3, or 7 (Cohort 2), enteral tube feeding (hazard: 0.35; 95%CI, 0.27-0.46) or hyperalimentation (hazard: 0.58; 95%CI, 0.38-0.90) was associated with improved survival in coma. Tube feeding was associated with decreased survival in acute respiratory failure (ARF) or multiorgan system failure (MOSF) with sepsis (hazard: 1.21; 95%CI, 10.4-1.41), cirrhosis (hazard: 2.15; 95%CI, 1.35-3.42), and COPD (hazard: 1.37; 95%CI, 1.04-1.80). Hyperalimentation was associated with decreased survival in ARF or MOSF with sepsis (hazard: 1.34; 95%CI, 1.12-1.59). CONCLUSIONS: Nutritional support was associated with improved survival in coma. Enteral feeding and hyperalimentation was associated with decreased survival in ARF or MOSF with sepsis. Tube feeding was associated with decreased survival in cirrhosis and COPD. Except for patients in coma, artificial nutrition was not associated with a survival advantage.

Adult↗

Dying with end stage liver disease with cirrhosis: insights from SUPPORT. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

OBJECTIVES: To understand patterns of care and end-of-life preferences for patients dying with end stage liver disease with cirrhosis (ESLDC). METHODS: Data were collected during the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT), a prospective cohort study of seriously ill hospitalized adults at five teaching hospitals in the United States, and included all patients enrolled in SUPPORT with ESLDC. RESULTS: Of 575 patients with ESLDC, 166 died during index hospitalization, and 168 died in the following year. The majority were male (65%) and white (80%); the median age was 52 years. Most rated their quality of life as poor or fair, and multiple comorbidities were common. Most spent their last few days completely disabled. Families often reported loss of most income and the need to leave work or other activities in order to care for patients. Pain was at least moderately severe most of the time in one-third of patients. End-of-life preferences were not associated with survival. Most patients (66.8%) preferred CPR, but DNR orders and orders against ventilator use increased near death. CONCLUSIONS: Patients with liver disease were young, likely to be male, and often had low incomes. The high burden of pain was comparable to that reported for patients with lung and colon cancer. Persons dying with liver disease may benefit from increased attention to relief of symptoms, improved home care, and advanced care planning.

Adult↗

Human rights and the AIDS crisis: the debate over resources.

In his plenary presentation of 11 July 2000 at the XIII International AIDS Conference, Kenneth Roth, the Executive Director of Human Rights Watch, the largest US-based human rights organization, reflects on whether a human-rights perspective can help us confront the AIDS crisis. More specifically, he asks the question whether human rights can help us meet the urgent challenge of securing the vast resources we need for treatment and prevention. Mr Roth believes they can. He argues that human rights are a powerful tool for meeting basic human needs, but that their contribution to the fight against AIDS is not as simple or straightforward as many often assume. In his presentation, he explains why.

Acquired Immunodeficiency Syndrome↗

Trocar and instrument positioning system TISKA. An assist device for endoscopic solo surgery.

The assistance received by the surgeon from support personnel during surgical laparoscopy is extremely important. This includes the retracting of instruments and the positioning of the endoscope. However, human assistance is costly and often does not provide satisfaction for the surgeon. The aim of the project was to develop a mechanical arm capable of manipulating a laparoscopic instrument under the control of the operating surgeon. The system design is based on a particular kinematic construction that maintains an invariant point of constraint motion coincident with the trocar puncture site through the abdominal wall. The guidance system allows transparent and intuitive operation, and its setup is easy and quick. It may be adapted either as an instrument retractor or as an optic positioning device. A new generation of instrument positioning systems, with improved ergonomy, will be a first step toward the diffusion of solo surgery techniques in minimally invasive therapy. We believe this prototype represents a valid compromise between human and robotic control for conventional laparoscopic instruments.

Animals↗

Regulated targeting of BAX to mitochondria.

The proapoptotic protein BAX contains a single predicted transmembrane domain at its COOH terminus. In unstimulated cells, BAX is located in the cytosol and in peripheral association with intracellular membranes including mitochondria, but inserts into mitochondrial membranes after a death signal. This failure to insert into mitochondrial membrane in the absence of a death signal correlates with repression of the transmembrane signal-anchor function of BAX by the NH2-terminal domain. Targeting can be instated by deleting the domain or by replacing the BAX transmembrane segment with that of BCL-2. In stimulated cells, the contribution of the NH2 terminus of BAX correlates with further exposure of this domain after membrane insertion of the protein. The peptidyl caspase inhibitor zVAD-fmk partly blocks the stimulated mitochondrial membrane insertion of BAX in vivo, which is consistent with the ability of apoptotic cell extracts to support mitochondrial targeting of BAX in vitro, dependent on activation of caspase(s). Taken together, our results suggest that regulated targeting of BAX to mitochondria in response to a death signal is mediated by discrete domains within the BAX polypeptide. The contribution of one or more caspases may reflect an initiation and/or amplification of this regulated targeting.

Amino Acid Chloromethyl Ketones↗

Vitamin E induces ramification and downregulation of adhesion molecules in cultured microglial cells.

Microglial cells in the healthy adult CNS possess a characteristic ramified morphology and show little or no expression of major histocompatibility complex (MHC) or adhesion molecules. In contrast, microglial cells isolated from newborn rat brains inevitably show a nonramified amoeboid morphology and express immunoeffector molecules, such as MHC class I and II, and various adhesion molecules thought to be markers of microglial activation. Furthermore, they produce large amounts of oxygen radicals. Treatment of cultured microglial cells with the antioxidants vitamin E (alpha-tocopherol) and vitamin C (ascorbic acid) induced a ramified microglial morphology after 48 h in vitro, otherwise only seen in healthy adult CNS tissue or in co-culture with astrocytes. Morphological transformation of microglial cells was quantified by morphometric analysis and was found to be statistically significant. Ramification of microglia induced by vitamin E was accompanied by downregulated expression of adhesion molecules leukocyte function antigen-1, very late antigen-4, and intercellular adhesion molecule-1, as assessed by FACS analysis and immunocytochemistry. Moreover, cell numbers of microglia treated with vitamin E remained stable within 7 days in vitro, whereas untreated controls showed a cell loss of 81.5%. These data show that vitamin E acts as a protective compound in dissociated microglial cell cultures. In conclusion, our results suggest that vitamin E and vitamin C shift microglial morphology toward ramification and induce an immunological deactivation. These changes seem to be mediated by oxidative mechanisms.

Animals↗

Patterns of mycobacterium avium culture and PCR positivity in immunodeficient HIV-infected patients: progression from localized to systematic disease, German Aids Study Group (GASG/IDKF).

Our aim was to establish the frequency and the longitudinal pattern of MAC culture positivity in late stage HIV-infected patients. Two other aims were to analyse risk factors for progression from localized to systemic disease and the value of PCR diagnosis using blood specimens. A total of 107 patients were recruited to be followed for 32 weeks. Prior MAC treatment and CD4 > 100/microliters were exclusion criteria. A total of 56 patients showed M. avium in at least 1 culture. 10/37 patients with MAC detected by culture first in 'non-sterile' specimens (stool, sputum) and urine progressed to systemic disease as determined by positive blood culture. Risk factors associated with this progression were a high symptom score at baseline, lymphadenopathy, anaemia, and low platelets. PCR was less sensitive than culture in detection of M. avium in blood specimens: Only 7/29 patients with positive blood cultures had a positive PCR at the same time. We conclude that symptomatic patients with advanced HIV-infection have a high frequency of MAC detection. Progression from localized to systemic culture positivity is associated with risk factors. Early 'pre-emptive' therapy is discussed.

Acquired Immunodeficiency Syndrome↗

Image analysis for comparative genomic hybridization based on a karyotyping program for windows.

OBJECTIVE: To describe the image processing and analysis techniques we developed for the quantitative analysis of comparative genomic hybridization (CGH). STUDY DESIGN: A system for CGH cytometry is based on a semiautomated karyotyping program using the Windows graphic user interface. RESULTS: After alignment and normalization of the fluorescence images of the test genome (FITC) and reference genome (TRITC), the chromosomes are segmented and arranged as a CGH karyogram. The CGH karyograms from different metaphases of one tumor sample are represented as a CGH sum karyogram. Mean DAPI, FITC, TRITC and RATIO images, as well as ratio profiles with the 95% confidence interval, can be displayed. CONCLUSION: Representation of CGH results in the form of pseudocolored mean ratio chromosomes enhances the visibility of the method. The ratio profile plus confidence interval facilitates the identification of preparation artifacts and the classification of chromosomal imbalances. The sum karyograms of several tumors can be combined into a CGH superkaryogram of a tumor subgroup; that helps identify recurrent DNA changes in a tumor and might lead to genetic tumor classification based on CGH.

DNA, Neoplasm↗