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PubMed2001

Twelve years of activity of the International Trichinella Reference Centre.

The ITRC is the official reference laboratory of both the International Commission on Trichinellosis (since 1988) and the International Office of Epizootics (since 1992). The ITRC was created as a repository for Trichinella strains and as a source of materials and information for international research in 1988. To date, about 900 isolates of human and animal origin from throughout the world have been examined and identified by new procedures developed at the ITRC or in collaboration with other institutions. Using material from this collection, the ITRC has provided a complete revision of the systematics of the genus Trichinella. The ITRC database can be consulted by accessing the web-site: www.simi.iss.it/trichinella/index.htm.

Animals↗

PubMed2000

The risks of transfusion-transmitted infection: direct estimation and mathematical modelling.

Direct measurement of the risk of transfusion-transmitted infection (TTI) is practical and accurate only if the level of risk is high. Historically, studies that established frozen repositories of transfusion recipient and/or blood donor samples were important in establishing the risk of many TTI agents, including the human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). However, given the current very low risk of TTI, mathematical modelling is necessary to estimate the magnitude of such a risk. For agents for which routine blood donor screening is performed, most of this risk comes from transfusion of units collected in the window period between donor infection and a positive blood screening assay. The incidence/window period model has been used to estimate the magnitude of such risks (of the order of 1:100 000 to 1:1 000 000) and for predicting the extent of risk reduction that can be expected with implementation of new tests. Direct estimation and mathematical modelling approaches are both important tools for future assessment of potential, new or emerging TTI agents.

Blood Donors↗

PubMed2005

Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn's disease.

BACKGROUND & AIMS: Antibody responses to certain microbial antigens define heterogeneous groups of Crohn's patients; multiple and high-level responses to these antigens are associated with aggressive clinical phenotypes. The flagellin, CBir1, identified by investigations in the C3H/HeJBir mouse model, has been identified as a dominant antigen capable of inducing colitis in mice and eliciting antibody responses in a subpopulation of patients with Crohn's disease (CD). The aim of this study was to evaluate serum response to CBir1 flagellin in CD patients and to compare this response to responses defined previously to oligomannan (anti-Saccharomyces cerevisiae antibody), I2, OmpC, and neutrophil nuclear autoantigens (pANCA), and to determine anti-CBir1-associated phenotypes. METHODS: A total of 484 sera from the Cedars Sinai Medical Center repository, previously typed for anti-Saccharomyces cerevisiae antibody, anti-I2, anti-OmpC, and pANCA were tested for anti-CBir1 by enzyme-linked immunosorbent assay, and results were assessed for clinical phenotype associations. RESULTS: The presence and level of immunoglobulin G anti-CBir1 were associated with CD independently. Anti-CBir1 was present in all antibody subgroups and expression increased in parallel with increases in the number of antibody responses. pANCA+ CD patients were more reactive to CBir1 than were pANCA+ ulcerative colitis patients. Anti-CBir1 expression is associated independently with small-bowel, internal-penetrating, and fibrostenosing disease features. CONCLUSIONS: Serum responses to CBir1 independently identify a unique subset of patients with complicated CD. This bacterial antigen was identified in a murine model and has a similar pattern of aberrant reactivity in a subset of CD patients.

Animals↗

PubMedDate not supplied

In vitro elution of gentamicin from Plaster of Paris beads.

OBJECTIVE: To determine the in vitro elution characteristics of gentamicin from Plaster of Paris-gentamicin (POP-gent) beads. STUDY DESIGN: In vitro, controlled, experimental study. METHODS: The POP-gent beads were made using a bead mold from 20 g calcium sulfate hemihydrate, 5 mL (500 mg) gentamicin solution, and 3 mL of phosphate buffered saline (PBS). Control beads were made similarly, using 30 g of dried powder and 8 mL of PBS. Beads were left in the mold overnight, gas-sterilized with ethylene oxide, and stored at room temperature for 5 months before testing. Bead chains were placed in sterile tubes containing porcine serum, and tubes were placed in a 37 degrees C incubator on a rocker. Serum was removed at intervals over 14 days and the concentration of gentamicin determined by fluorescent polarization immunoassay. Serum antibacterial activity was determined against an equine origin Escherichia coli. RESULTS: POP-gent beads released gentamicin for the 14-day sampling period. Eighty percent of the gentamicin incorporated in the beads was released over the first 48 hours. Eluent from POP-gent beads inhibited the growth of E coli at all time periods. No gentamicin was eluted from control beads and control eluent did not inhibit growth of E coli. CONCLUSIONS: In this experimental model, POP-gent beads released bactericidal drug for 14 days. Eighty percent of the gentamicin incorporated into the beads was released during the first 48 hours. The drug retains its bactericidal activity after ethylene oxide sterilization and storage at room temperature for up to 5 months. CLINICAL RELEVANCE: Pop-gent beads may be a useful repository device to deliver gentamicin locally in tissues.

Animals↗

PubMed2001

Development and utilization of paperless medical records: a unique approach.

The purpose of this article is to describe the development and utilization of a unique paperless medical record system in a large multispeciality group practice setting. The Scott and White integrated health care delivery system provides care over a 34-county area in Central Texas. Since 1988, clinicians at Scott and White have developed a text-based, content-searchable electronic medical record system known as EMRx. This system provides a single clinical data repository that allows patient care activities and aggregate data analyses to occur by using the same set of data on a daily basis. Use of this approach has led to the aggregation of over 9.8 million clinical documents since 1994. Over 1,845 health care providers used the system during May 2000 for direct patient care; 866,114 patient records have been accessed since January 1, 1999 to answer questions related to patient care, quality assurance, outcomes research, and accreditation.

Group Practice↗

PubMed2000

[Physician's anxiety and physician's elegance. Problems in dealing with cost reduction, education of general practitioners and optimal size of practice networks in a cross-national comparison].

The key reason for physicians networking in managed care is to get a better coping with uncertainty on action (treatment) decisions. The second reason for networking in managed care are financial benefits grounds. But this reason is very ambivalent. Three different action problems (role conflicts) in managed care network are to solved, which was also in single practices. In the lecture the decision strategies and decision resources has been compared. Observations are done using expert interviews, patient interviews and analysis of documents in USA, Germany and Switzerland. The first problem is the choosing of a cost reduction strategy which is not reducing the effectiveness. Such "ugly" solution strategies like exclusion of "expensive" patients and a rationing of necessary medical services in a kind of McDonalds network of physicians will fail the target. The optimost way is a saving of all unnecessary medical even injourious performances. The chosen cost reduction strategy is not real visible from outside but in fact limited cognizable and controllable. Evidence based health care can be a resource of treatment decisions and could train such decisions but it will not substitute these decisions. The second problem is the making of real family practitioners as gatekeepers. Knowledge about the care system is still not making a real family practitioner, even if this is the minimum condition of their work. Also contractual relationships between insurance and doctor as a gatekeeper or financial incentives for patients are still making not a real family practitioner as a gatekpeeper. Only throughout the trust of patients supported by second opinions is making the real family practitioner as a gatekeeper. "Doctor hopping" could be the reaction by scarcity of trustworthy family practitioners as gatekeepers. The third problem is the choosing of the optimal scale of a network due to the very different optimal size of networks regarding the requirement of risk spreeds, of the motivated engagement, of competition, incentives of inclusion of insurantes, they always need other net sizes. But it is possible, for each requirement there could function different networks. A practice (doctor's office) can be a member in different networks in several levels. The social transition from a small office to a network of offices is in all business lines a cultural shock involving not only benefits also psychical and social distress. In this there is no difference between health or agriculture or each other business of trade and industry. The destiny of the joint doctor's offices in Germany suggest due to a very serious power to scatter this networks. The comparative analysis of conflicts, strains, resources and strategies of associations and networks could yield from a developed methodical repository in sociology and social psychology what exists since 40 years (see also Meyer--in this journal). But therefore must be included also the action problems, which are only mentioned in passing of the according profession horizon.

Cost Control↗

PubMed2001

Relaxin causes changes of the liver. In vivo studies in rats.

During pregnancy, the liver undergoes metabolic adjustments directed to fulfil the needs of the mother and the growing fetus. This study was designed to verify whether relaxin, a hormone related to pregnancy, may induce histochemical and ultrastructural modifications of hepatocytes which can be related to metabolic changes. Estrogen-primed female rats were treated with relaxin (10 microg in repository vehicle) for 18 h. Additional male rats were treated with relaxin (10 microg/day in PBS) for 4 days. Appropriate vehicle-treated rats were used as controls. After fasting, the rats were killed and liver fragments were processed for light and electron microscopy and for computer-assisted morphometry of PAS-positive glycogen deposits and acid phosphatase-reactive organelles. In both sexes, the relaxin-treated rats underwent a significant decrease in the amount of glycogen in the hepatocytes as compared with the controls. These changes were accompanied by an increase in smooth endoplasmic reticulum, endocytosis vesicles and lysosomes. These findings show that relaxin promotes glycogen depletion and induces morphological changes of hepatocytes which are consistent with functional activation. It is suggested that relaxin might play an important role in hepatic metabolic adjustments occurring during pregnancy.

Animals↗

PubMed2005

A pooled analysis to evaluate results of capsule endoscopy trials.

BACKGROUND AND STUDY AIM: Capsule endoscopy is a new tool in the evaluation of the small intestine. To speed evaluation and acceptance of this technology, the manufacturer (Given Imaging Ltd, Yoqneam, Israel) funded several trials. The data from these trials were collected at a central repository using a standardized reporting tool. Presentation of this data to the US Food and Drug Administration (FDA) in July 2003 led to the removal of the adjunctive term with regard to indication for capsule endoscopy, recognizing that the method is of independent importance for evaluating the small bowel. The aim of the present study was to combine the data from several capsule trials to help determine the yield and miss rate of capsule endoscopy for different diseases, compared with alternative diagnostic modalities. METHODS: Capsule studies were identified from a master database of funded studies. Studies were included in the pooled analysis if they reported a prospective comparison with another modality for evaluation of the small intestine. RESULTS: 32 studies with a total of 691 patients were found in the master database, of which 24 studies, representing 530 patients, met inclusion criteria and were entered into the pooled analysis. Prior to study entry, patients had undergone a mean of 6.77 diagnostic procedures, without findings. Of these 24 studies, 14 (involving 310 patients) were categorized as "bleeding" studies, and 10 studies (220 patients) as "nonbleeding small-bowel disorders" studies. The comparison procedure was push enteroscopy in 300 patients (in 45 for nonbleeding disorders), small-bowel series in 140 patients (in 125 for non-bleeding disorders), and colonoscopy with ileoscopy in 90 patients (50 for nonbleeding disorders). Overall analysis per patient showed new findings from capsule endoscopy in 50 % of patients; 17 % had new findings from the comparison method; in 22 % there were similar findings; and in 11 % there were no findings. A total of 1349 instances of disease were identified in the 530 examinations. Capsule endoscopy solely detected 87 % of the disease instances, while the comparison method solely detected 13 %. The yield for push enteroscopy alone was 14.8 %, for small-bowel series it was 9.9 %, and for colonoscopy it was 13.2 %. Capsule endoscopy missed 146 disease instances for a miss rate of 10 %; 989 were missed by the comparison methods for a miss rate of 73 %; and 214 were detected by both methods. CONCLUSION: Capsule endoscopy is the state of the art method for noninvasive detection of small-bowel disease.

Adolescent↗

PubMed2005

Modulation of the G2 cell cycle checkpoint by sesquiterpene lactones psilostachyins A and C isolated from the common ragweed Ambrosia artemisiifolia.

A phenotypic cell-based assay for inhibitors of the G (2) DNA damage checkpoint was used to screen plant extracts from the US National Cancer Institute Natural Products Repository. It revealed activity in a methanol extract from the common ragweed Ambrosia artemisiifolia. Assay-guided fractionation led to the identification of the sesquiterpene lactones psilostachyins A and C as novel checkpoint inhibitors. Elimination of their alpha,beta-unsaturated carbonyl group caused a loss of activity, suggesting that the compounds can bind covalently to target proteins through Michael addition. Psilostachyins A and C also blocked cells in mitosis and caused the formation of aberrant microtubule spindles. However, the compounds did not interfere with microtubule polymerization in vitro. The related sesquiterpene lactones psilostachyin B, paulitin and isopaulitin were also isolated from the same extract but showed no checkpoint inhibition. The identification of the target(s) of psilostachyins A and C may provide further insight into the signalling pathways involved in cell cycle arrest and mitotic progression.

Ambrosia↗

PubMed1990

Screening of selected male blood donors for p24 antigen of human immunodeficiency virus type 1. The Transfusion Safety Study Group.

BACKGROUND: The p24 antigen of human immunodeficiency virus type 1 (HIV-1) is sometimes detected before antibody (anti-HIV-1) is detectable in the serum of recently infected persons. This has led to the consideration of p24-antigen testing for routine screening of blood donors. METHODS: To estimate how many HIV-infected seronegative donors would be identified if p24-antigen screening was introduced, we tested selected donations from a repository of 200,000 serum samples from voluntary donors that was established in late 1984 and early 1985. The 8597 serum samples selected for p24-antigen screening were chosen because their donors had demographic characteristics known to be associated with a high prevalence of seropositivity. RESULTS: The prevalence of anti-HIV-1 antibodies in the 1984-1985 serum samples selected for p24-antigen screening was 1.54 percent--more than 100 times the 0.012 percent prevalence in present-day donations in the United States. The antigen was detected in 15 of 132 serum samples (11.4 percent) from donors who had already been confirmed as seropositive. No instance of confirmed positivity for p24 antigen was found among the 8465 seronegative serum samples. CONCLUSIONS: These data indicate that the yield of screening for p24 antigen in volunteer donors to identify HIV-1 carriers would be negligible. We therefore recommend against routine screening with currently available p24-antigen assays.

Blood Donors↗

PubMed2003

Development of autoantibodies before the clinical onset of systemic lupus erythematosus.

BACKGROUND: Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of autoantibody development before the clinical diagnosis. METHODS: The Department of Defense Serum Repository contains approximately 30 million specimens prospectively collected from more than 5 million U.S. Armed Forces personnel. We evaluated serum samples obtained from 130 persons before they received a diagnosis of SLE, along with samples from matched controls. RESULTS: In 115 of the 130 patients with SLE (88 percent), at least one SLE autoantibody tested was present before the diagnosis (up to 9.4 years earlier; mean, 3.3 years). Antinuclear antibodies were present in 78 percent (at a dilution of 1:120 or more), anti-double-stranded DNA antibodies in 55 percent, anti-Ro antibodies in 47 percent, anti-La antibodies in 34 percent, anti-Sm antibodies in 32 percent, anti-nuclear ribonucleoprotein antibodies in 26 percent, and antiphospholipid antibodies in 18 percent. Antinuclear, antiphospholipid antibodies, anti-Ro, and anti-La antibodies were present earlier than anti-Sm and anti-nuclear ribonucleoprotein antibodies (a mean of 3.4 years before the diagnosis vs. 1.2 years, P=0.005). Anti-double-stranded DNA antibodies, with a mean onset 2.2 years before the diagnosis, were found later than antinuclear antibodies (P=0.06) and earlier than anti-nuclear ribonucleoprotein antibodies (P=0.005). For many patients, the earliest available serum sample was positive; therefore, these measures of the average time from the first positive antibody test to the diagnosis are underestimates of the time from the development of antibodies to the diagnosis. Of the 130 initial matched controls, 3.8 percent were positive for one or more autoantibodies. CONCLUSIONS: Autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibodies in patients with SLE tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic.

Antibodies, Antinuclear↗

PubMed2003

Protecting research subjects under the waiver of informed consent for emergency research: experiences with efforts to inform the community.

STUDY OBJECTIVES: The US Food and Drug Administration (FDA) and Department of Health and Human Services created a method for obtaining a waiver of informed consent to permit research in emergency settings when patients are not competent. One of the requirements to obtain a waiver is public disclosure about the research. We describe approaches used to meet the public disclosure requirement. METHODS: We performed a qualitative content analysis of the FDA's repository for mandatory documentation of public disclosure efforts as of November 1999. Data from 4 studies were analyzed: 2 multi-institutional trials involving trauma and 2 smaller trials involving cardiac arrest. These efforts included both 1-way communications, such as announcements, and 2-way communications, such as focus groups and public meetings. Participation in and common concerns expressed during 2-way communications were noted, as was evidence of mechanisms of advance refusal and the collection of quantitative data on public opinion. RESULTS: One-way communications were the predominant method of disclosure. Many 2-way communications were not directed toward lay persons. Those that were often involved fewer than 15 participants. Concerns regarding inability to refuse study participation, racial biases affecting study design and execution, and ambiguity with regard to how community input would be used in study decision making were raised in several 2-way communications. A minority of participating hospitals announced mechanisms of advance refusal or collected quantitative data on public opinion concerning proposed research. CONCLUSION: Initial experience with obtaining a waiver of informed consent for emergency research suggests that community involvement and specific public concerns should be carefully considered in future applications for such a waiver.

Cardiopulmonary Resuscitation↗

PubMed2002

Virtual temporal bone dissection: an interactive surgical simulator.

OBJECTIVE: Our goal was to integrate current and emerging technology in virtual systems to provide a temporal bone dissection simulator that allows the user interactivity and realism similar to the cadaver laboratory. STUDY DESIGN: Iterative design and validation of a virtual environment for simulating temporal bone dissection. SETTING: University otolaryngology training program with interdisciplinary interaction in a high-performance computer facility. RESULTS: The system provides visual, force feedback (haptic), and aural interfaces. Unlike previous "fly through" virtual systems, this environment provides a richer emulation of surgical experience. CONCLUSION: The system provides a high level of functional utility and, through initial evaluations, demonstrates promise in adding to traditional training methods. SIGNIFICANCE: The system provides an environment to learn temporal bone surgery in a way similar to the experience with cadaver material where the subject is able to interact with the data without constraints (nondeterministic). Eventually, it may provide the "front end" to a large repository of various temporal bone pathologies that can be accessed through the Internet.

Algorithms↗

PubMed2005

Intracellular Helicobacter pylori in gastric epithelial progenitors.

Helicobacter pylori is generally viewed as an extracellular pathogen. We have analyzed the tropism of H. pylori clinical isolates in a gnotobiotic transgenic mouse model of human chronic atrophic gastritis, a preneoplastic condition. These mice lack acid-producing parietal cells and have an amplified population of dividing gastric epithelial progenitors (GEPs) that express NeuAc alpha 2,3Gal beta 1,4-glycans recognized by H. pylori adhesins. Scanning confocal and transmission electron microscopic studies of stomachs that had been colonized for 1 month or 1 year revealed intracellular bacterial collections (IBCs) in a small subset of multi- and oligopotential epithelial progenitors. Transmission electron microscopic and multilabel immunohistochemical analyses disclosed bacteria with several morphotypes, including spiral-shaped, in the cytoplasm and endosomes. Several stages in IBC evolution were documented, from a few solitary bacteria to consolidated populations in dividing and nondividing GEPs, to microorganisms traversing breaches in the GEP plasma cell membrane. IBC formation was not a unique feature of H. pylori strains isolated from patients with chronic atrophic gastritis. The notion that adult mammalian epithelial progenitors can function as a repository for H. pylori broadens the view of host habitats available to this and perhaps other pathogens.

Animals↗

PubMed2005

Evolution of carbon sinks in a changing climate.

Climate change is expected to influence the capacities of the land and oceans to act as repositories for anthropogenic CO2 and hence provide a feedback to climate change. A series of experiments with the National Center for Atmospheric Research-Climate System Model 1 coupled carbon-climate model shows that carbon sink strengths vary with the rate of fossil fuel emissions, so that carbon storage capacities of the land and oceans decrease and climate warming accelerates with faster CO2 emissions. Furthermore, there is a positive feedback between the carbon and climate systems, so that climate warming acts to increase the airborne fraction of anthropogenic CO2 and amplify the climate change itself. Globally, the amplification is small at the end of the 21st century in this model because of its low transient climate response and the near-cancellation between large regional changes in the hydrologic and ecosystem responses. Analysis of our results in the context of comparable models suggests that destabilization of the tropical land sink is qualitatively robust, although its degree is uncertain.

Atmosphere↗

PubMed2006

Metal stocks and sustainability.

The relative proportions of metal residing in ore in the lithosphere, in use in products providing services, and in waste deposits measure our progress from exclusive use of virgin ore toward full dependence on sustained use of recycled metal. In the U.S. at present, the copper contents of these three repositories are roughly equivalent, but metal in service continues to increase. Providing today's developed-country level of services for copper worldwide (as well as for zinc and, perhaps, platinum) would appear to require conversion of essentially all of the ore in the lithosphere to stock-in-use plus near-complete recycling of the metals from that point forward.

Conservation of Natural Resources↗

PubMed2006

An internally controlled peripheral biomarker for Alzheimer's disease: Erk1 and Erk2 responses to the inflammatory signal bradykinin.

Cognitive impairment has recently been found to correlate with changes in peripheral inflammatory signals such as TNF-alpha and IL-1beta. PKC isozymes regulate levels of TNF-alpha and IL-6 and the release of other cytokines and also show deficits in Alzheimer's disease (AD) brains and skin fibroblasts. Here, we investigate MAPK Erk1 and Erk2 phosphorylation in response to the inflammatory agonist bradykinin, which activates PKC pathways. An internally controlled comparison of Erk1 and Erk2 produced an AD index that accurately distinguished fibroblasts of AD from those of normal controls and of non-AD dementias. This accuracy was demonstrated for Coriell Cell Repository (Coriell Institute of Medical Research, Camden, NJ) samples, as well as for samples analyzed on gels with autopsy diagnostic confirmation. AD Erk1 and Erk2 index values were inversely correlated with disease duration, suggesting maximal efficacy for early diagnosis. Finally, the results also demonstrate that, when the AD index agreed with the clinical diagnosis on the presence of AD, there was a high probability of accuracy based on autopsy validation. Thus, this peripheral molecular biomarker, based on differential Erk1 and Erk2 phosphorylation, could have important clinical utility for providing increased certainty in the positive diagnosis of AD, particularly in the early phase of disease progression.

Alzheimer Disease↗

PubMed1981

Induction of terminal deoxynucleotidyl transferase and Lyt antigens with thymosin: identification of multiple subsets of prothymocytes in mouse bone marrow and spleen.

Thymosin (fraction 5 and synthetic alpha 1 peptide) induced prothymocytes in mouse bone marrow and spleen to express terminal deoxynucleotidyl transferase (TdT; DNA nucleotidylexotransferase; nucleosidetriphosphate:DNA deoxynucleotidylexotransferase, EC 2.7.7.31) or Lyt-1+, 2+, 3+ alloantigens (or both) after brief incubation in vitro. Three antigenic phenotypes were generated: (i) TdT+ Lyt+, (ii) TdT- Lyt+, and (iii) TdT+ Lyt-. The TdT+ Lyt+ phenotype was expressed by 80% of prothymocytes in bone marrow and 30% of prothymocytes in spleen from normal mice. The TdT- Lyt+ phenotype was expressed by 81% of prothymocytes in bone marrow from athymic mice. More than 80% of TdT+ bone marrow cells from normal and athymic mice expressed Lyt antigens after thymosin treatment. We interpret these observations as suggesting that (i) most TdT+ hemopoietic cells in normal and athymic mice are thymocyte progenitors; (ii) two independent lineages of prothymocytes exist, one that expresses TdT and another that does not, (iii) commitment of prothymocytes to the TdT+ cell pathway is partially regulated by a thymic feedback mechanism; and (iv) the bone marrow preferentially produces TdT+ prothymocytes, whereas the spleen may serve as a repository for TdT- prothymocytes. A model of T-cell development is presented in which the thymus functions as a compound organ to process TdT+ and TdT- thymocytes progenitors and to generate two lines of T cells.

Animals↗