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1.
J Vet Cardiol ; 39: 22-34, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34963075

ABSTRACT

INTRODUCTION/OBJECTIVES: The objectives were to conduct a survey of cardiologists on their recent experiences with cats that have dilated cardiomyopathy (DCM) and to retrospectively review individual cases of feline DCM. ANIMALS, MATERIALS AND METHODS: Part one: A survey was distributed to cardiologists with questions regarding caseload and clinical management of cats with DCM diagnosed over the past two years. Part two: Cardiologists completing the survey were invited to submit data from cats recently diagnosed with DCM. Data on signalment, clinical signs, diet, echocardiographic measurements and outcome were recorded. RESULTS: Part one: From 52 completed surveys, many cardiologists responded that measuring and supplementing taurine and recommending a diet change in cats with DCM are common practices. Few (15%) cardiologists reported an increase in the number of feline DCM cases over the past two years, although some had cases that improved even if taurine deficiency was not present. Part two: Twenty of 37 (54%) cats ate low pea/lentil (low PL) diets, and 14/37 (38%) ate high PL diets at the time of diagnosis; three had incomplete diet information. Two of 13 cats (15%) in which taurine was measured had levels below the reference range. After adjusting for other variables, cats eating high PL diets that changed diets after diagnosis had a significantly longer survival time than that of cats eating high PL diets that did not change diets after diagnosis (P = 0.025). CONCLUSIONS: Additional research is warranted to determine whether there could be a possible association between diet and DCM in cats.


Subject(s)
Cardiologists , Cardiomyopathy, Dilated , Cat Diseases , Animals , Cardiomyopathy, Dilated/veterinary , Cat Diseases/epidemiology , Cat Diseases/etiology , Cats , Diet/veterinary , Dogs , Humans , Retrospective Studies
2.
World J Microbiol Biotechnol ; 36(3): 42, 2020 Mar 04.
Article in English | MEDLINE | ID: mdl-32130551

ABSTRACT

Photobioreactors (PBRs) are equipment of central importance for the massive cultivation of microalgae, providing controlled conditions for high cell productivity. There are a few popular PBR designs, with contrasting advantages and limitations, such as poor light distribution, mass transfer, or hydrodynamic behavior. Due to the environmental concerns in recent decades and the discovery of new, useful microalgal metabolites, the interest in finding alternatives to solve technological bottlenecks of PBRs has intensified. In this process, new geometries, materials, and modes of light supply were developed, generating a significant scientific and technological output, reported in papers and patents. We present a technological landscape analysis of photobioreactor design, focusing on improvements of the classical geometries and trends in industrial photobioreactors. The analysis of 412 patent documents showed a surge in innovation filing since 2005 and a reduction in the number of new documents along the last decade. The recent efforts in design improvement, the leading countries, institutes and companies that innovate, and the trends in PBR technology are presented and discussed.


Subject(s)
Equipment Design/methods , Microalgae/growth & development , Photobioreactors/microbiology , Biomass , Hydrodynamics , Patents as Topic
3.
Osteoporos Int ; 29(4): 953-960, 2018 04.
Article in English | MEDLINE | ID: mdl-29429033

ABSTRACT

PURPOSE: Although half of women and one-quarter of men aged 50 and older will sustain an acute low-trauma fracture, less than a quarter receive appropriate secondary fracture prevention. The goal of this quality improvement demonstration project was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in three open health care systems aided by a cloud-based tool. METHODS: The pre-post study design examined the proportion of men and women over age 50 who received appropriate assessment (bone mineral density, vitamin D levels) and treatment (calcium/vitamin D, pharmacologic therapy) in the six months following a recently diagnosed fracture. The pre-study (Pre FLS) included a retrospective chart review for baseline data (N = 344 patients) within each health care system. In the post-evaluation (Post FLS, N = 148 patients), the FLS coordinator from each health care system examined these parameters following enrollment and for 6 months following the recently diagnosed fracture. Data were managed in the cloud-based FLS application tool. RESULTS: Ninety-three participants completed the program. The FLS program increased the percentage of patients receiving bone mineral density testing from 21% at baseline to 93% (p < 0.001) Post FLS implementation. Assessments of vitamin D levels increased from 25 to 84% (p < 0.001). Patients prescribed calcium/vitamin D increased from 36% at baseline to 93% (p < 0.001) and those prescribed pharmacologic treatment for osteoporosis increased on average from 20 to 54% (p < 0.001) Post FLS. CONCLUSIONS: We conclude that the FLS model of care in an open health care system, assisted by a cloud-based tool, significantly improved assessment and/or treatment of patients with a recently diagnosed osteoporotic fracture. Future studies are necessary to determine if this model of care is scalable and if such programs result in prevention of fractures. Mini-Abstract: The goal was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in open health care systems aided by a cloud-based tool. This model significantly improved assessment and/or treatment of patients with a recently diagnosed fracture.


Subject(s)
Delivery of Health Care, Integrated/organization & administration , Models, Organizational , Osteoporotic Fractures/prevention & control , Absorptiometry, Photon/methods , Aged , Bone Density/physiology , Bone Density Conservation Agents/therapeutic use , Calcium/therapeutic use , Cloud Computing , Dietary Supplements , Drug Utilization/statistics & numerical data , Female , Humans , Male , Middle Aged , Osteoporosis/diagnosis , Osteoporosis/drug therapy , Osteoporosis/physiopathology , Osteoporotic Fractures/physiopathology , Retrospective Studies , Secondary Prevention/organization & administration , United States , Vitamin D/therapeutic use
4.
Osteoporos Int ; 27(2): 683-90, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26286624

ABSTRACT

UNLABELLED: The aims of this study are to develop a cloud-based application of the Fracture Liaison Service for practitioners to coordinate the care of osteoporotic patients after suffering primary fractures and provide a performance feedback portal for practitioners to determine quality of care. The application provides continuity of care, improved patient outcomes, and reduced medical costs. INTRODUCTION: The purpose of this study is to describe the content development and functionality of a cloud-based application to broadly deploy the Fracture Liaison Service (FLS) to coordinate post-fracture care for osteoporotic patients. METHODS: The Bone Health Collaborative developed the FLS application in 2013 to support practitioners' access to information and management of patients and provide a feedback portal for practitioners to track their performance in providing quality care. A five-step protocol (identify, inform, initiate, investigate, and iterate) organized osteoporotic post-fracture care-related tasks and timelines for the application. A range of descriptive data about the patient, their medical condition, therapies and care, and current providers can be collected. Seven quality of care measures from the National Quality Forum, The Joint Commission, and the Centers for Medicare and Medicaid Services can be tracked through the application. RESULTS: There are five functional areas including home, tasks, measures, improvement, and data. The home, tasks, and data pages are used to enter patient information and coordinate care using the five-step protocol. Measures and improvement pages are used to enter quality measures and provide practitioners with continuous performance feedback. The application resides within a portal, running on a multitenant, private cloud-based Avedis enterprise registry platform. All data are encrypted in transit and users access the application using a password from any common web browser. CONCLUSION: The application could spread the FLS model of care across the US health care system, provide continuity of care, effectively manage osteoporotic patients, improve outcomes, and reduce medical costs.


Subject(s)
Cloud Computing , Delivery of Health Care, Integrated/organization & administration , Models, Organizational , Osteoporotic Fractures/prevention & control , Bone Density Conservation Agents/therapeutic use , Clinical Protocols , Delivery of Health Care, Integrated/standards , Humans , Intersectoral Collaboration , Osteoporosis/drug therapy , Secondary Prevention/organization & administration , Secondary Prevention/standards , United States
5.
Bioresour Technol ; 200: 374-9, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26512861

ABSTRACT

The red yeast Sporobolomyces ruberrimus H110 was able to use glycerol as a carbon source. The highest concentration (0.51gL(-1)) and productivity (0.0064gL(-1)h(-1)) of carotenoids were achieved when raw glycerol from biodiesel production, containing around 1gL(-1) of fatty acids, was used as the carbon source, which represented increases of 27% and 1.5×, respectively, in relation to pure glycerol. Mass spectrometry analysis led to the identification of four carotenoids in the fermented samples, torularhodin, torulene, ß-carotene and γ-carotene. The use of raw glycerol also enhanced the proportion of torularhodin (69% against 59% in pure glycerol). The addition of individual fatty acids (palmitic, stearic, oleic and linoleic acids) to pure glycerol resulted in increases between 15% and 25% in maximum concentration and between 1.6× and 2.0× in productivity of carotenoids. The presence of palmitic and oleic acids increased the torularhodin proportion to 66%.


Subject(s)
Basidiomycota/metabolism , Carotenoids/biosynthesis , Glycerol/chemistry , beta Carotene/biosynthesis , Biofuels , Bioreactors , Chromatography, Gas , Chromatography, High Pressure Liquid , Fatty Acids/analysis , Fatty Acids/chemistry , Fermentation , Linoleic Acids/chemistry , Mass Spectrometry , Oleic Acids/chemistry , Palmitic Acids/chemistry , Stearic Acids/chemistry
6.
Am J Transplant ; 13(2): 450-7, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23205926

ABSTRACT

Most centers utilize phone or written surveys to screen candidates who self-refer to be living kidney donors. To increase efficiency and reduce resource utilization, we developed a web-based application to screen kidney donor candidates. The aim of this study was to evaluate the use of this web-based application. Method and time of referral were tabulated and descriptive statistics summarized demographic characteristics. Time series analyses evaluated use over time. Between January 1, 2011 and March 31, 2012, 1200 candidates self-referred to be living kidney donors at our center. Eight hundred one candidates (67%) completed the web-based survey and 399 (33%) completed a phone survey. Thirty-nine percent of donors accessed the application on nights and weekends. Postimplementation of the web-based application, there was a statistically significant increase (p < 0.001) in the number of self-referrals via the web-based application as opposed to telephone contact. Also, there was a significant increase (p = 0.025) in the total number of self-referrals post-implementation from 61 to 116 per month. An interactive web-based application is an effective strategy for the initial screening of donor candidates. The web-based application increased the ability to interface with donors, process them efficiently and ultimately increased donor self-referral at our center.


Subject(s)
Internet , Kidney Transplantation/methods , Tissue and Organ Procurement/methods , Adult , Body Mass Index , Cohort Studies , Female , Humans , Living Donors , Male , Middle Aged , Models, Statistical , Patient Education as Topic , Program Development , Referral and Consultation , Renal Insufficiency/therapy , Retrospective Studies , Software
7.
Bioresour Technol ; 118: 603-6, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22704830

ABSTRACT

Phytase production by Aspergillus niger F3 by solid state fermentation (SSF) on citrus peel was evaluated at pilot scale under different aeration conditions. The best airflow intensity was 1 VkgM (Lair kg medium(-1) min(-1)), which allowed to produce 65 units of phytases per gram in dry basis (65 Ug(-1) d.b.) as it removed the metabolic heat generated by the microorganism, Agitation did not improve heat removal. Airflow intensity was considered as scale-up criterion. When the airflow intensity was maintained at 1 VkgM for SSF with 2 and 20 kg of medium, the kinetics parameters for biomass and enzyme concentration at the end of fermentation differed by less than 2. The air flow intensity was required to maintain the temperature and cool the SSF and to provide oxygen for microbial growth. Air flow intensity is a key a factor that must be considered when scale-up of SSF is attempted.


Subject(s)
6-Phytase/biosynthesis , Air Movements , Aspergillus niger/enzymology , Biotechnology/methods , Fermentation/physiology , Aerobiosis , Hot Temperature , Kinetics
8.
Am J Transplant ; 11(11): 2308-16, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21967066

ABSTRACT

Breakthroughs in basic and clinical science in solid organ transplantation were presented at the American Transplant Congress 2011. Key areas of presentation included the pathogenesis of late allograft failure, immune regulation and tolerance, pathways in allograft injury, electing appropriate patients for transplantation, determining the best allocation schemes to maximize effective utilization, organ preservation, monitoring the alloimmune response and immunosuppressive management. In this review, we present highlights of the meeting. These presentations demonstrate the exciting promise in translating from the bench to affect patient care.


Subject(s)
Organ Transplantation , Graft Rejection/etiology , Humans , Immune Tolerance/physiology , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Organ Preservation , Tissue Donors/supply & distribution , Transplantation Immunology , Transplantation, Homologous , Treatment Failure
9.
Haemophilia ; 17(1): 118-23, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20738412

ABSTRACT

Severe haemophilic arthropathy of the elbow is a significant cause of morbidity among adults with haemophilia. However, previous reports of total elbow arthroplasty (TEA) in the haemophilic population have been based on small numbers of patients with relatively short-term follow-up. The records of seven total elbow arthroplasties in six adult men with haemophilia at the University of California, San Francisco who underwent TEA over a period of 25 years were retrospectively reviewed. Type of haemophilia, age at time of TEA, HIV infection status, pre- and postoperative range-of-motion (ROM) scores, complications (including infections), need for subsequent surgical revision and functional outcomes were recorded. Four patients had severe factor VIII deficiency and two patients had severe factor IX deficiency. None of the patients had an inhibitor. The mean age at the time of surgery was 34 years (range, 22-46 years) and the mean follow-up period was 118 months (range, 37-176 months). One of the six patients had TEA in both elbows. Five of the six patients were infected with HIV. There were no immediate perioperative complications. At a mean of 19.2 months postoperatively, ROM had improved in five of seven TEAs: mean flexion had increased from 110.7° (SD = 15.0) to 120.1° (SD = 14.5), whereas mean preoperative extension increased from -44.3° (SD = 21.5) to -36.9° (SD = 27.0). One patient required a revision at 30 months because of ulnar component loosening. This same patient sustained a staph epidermidis infection and ultimate removal of the prosthesis 15 years postoperatively. At a mean of 118 months postoperatively, five of six patients continued to report reduced pain and preserved functionality, with ability to perform normal daily activities. TEA resulted in favourable results in six of seven procedures. Our findings support the viability of TEA for individuals with severe haemophilic arthropathy of the elbow, especially to reduce pain and preserve or restore functionality.


Subject(s)
Arthroplasty, Replacement, Elbow , Hemophilia A/surgery , Hemophilia B/surgery , Adult , Hemophilia A/physiopathology , Hemophilia B/physiopathology , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Pain Measurement , Postoperative Complications , Range of Motion, Articular , Retrospective Studies , Young Adult
10.
Am J Transplant ; 10(1): 115-23, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19958332

ABSTRACT

Organs from donors after cardiac death (DCD) are being increasingly utilized. Prior reports of DCD kidney transplantation involve the use of prednisone-based immunosuppression. We report our experience with early corticosteroid withdrawal (ECSW). Data on 63 DCD kidney transplants performed between 2002 and 2007 were analyzed. We compared outcomes in 28 recipients maintained on long-term corticosteroids (LTCSs) with 35 recipients that underwent ECSW. DGF occurred in 49% of patients on ECSW and 46% on LTCS (p=0.8). There was no difference between groups for serum creatinine or estimated GFR between 1 and 36 months posttransplant. Acute rejection rates at 1 year were 11.4% and 21.4% for the ECSW and LTCS group (p=0.2). Graft survival at 1 and 3 years was 94% and 91% for the ECSW group versus 82% and 78% for the LTCS group (p>or=0.1). Death censored graft survival was significantly better at last follow-up for the ECSW group (p=0.02). Multivariate analysis revealed no correlation between the use of corticosteroids and survival outcomes. In conclusion, ECSW can be used successfully in DCD kidney transplantation with no worse outcomes in DGF, rejection, graft loss or the combined outcome of death and graft loss compared to patients receiving LTCS.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/methods , Adult , Cadaver , Creatinine/blood , Death , Female , Glomerular Filtration Rate , Graft Rejection/prevention & control , Graft Survival/drug effects , Humans , Kidney Transplantation/mortality , Kidney Transplantation/physiology , Male , Middle Aged , Retrospective Studies , Time Factors , Tissue Donors , Treatment Outcome
11.
Am J Transplant ; 9(9): 1973-80, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19563334

ABSTRACT

Recent advances in our understanding of the basic mechanisms that control liver regeneration and repair will produce the next generation of therapies for human liver disease. Insights gained from large-scale genetic analysis are producing a new framework within which to plan interventions. Identification of specific molecules that drive regeneration will increase the options for live-donor liver transplantation, and help treat patients with small-for-size syndrome or large tumors who would otherwise have inadequate residual mass after resection. In a complementary fashion, breakthroughs in the ability to manipulate various cell types to adopt the hepatocyte or cholangiocyte phenotype promise to revolutionize therapy for acute liver failure and metabolic liver disease. Finally, elucidating the complex interactions of liver cells with each other and various matrix components during the response to injury is essential for fabricating a liver replacement device. This focused review will discuss how a variety of important scientific advances are likely to impact the treatment of specific types of liver disease.


Subject(s)
Liver Diseases/therapy , Liver Transplantation/methods , Liver/pathology , Regeneration , Animals , Bilirubin/metabolism , Blood Platelets/cytology , Cytokines/metabolism , Extracellular Matrix/metabolism , Hepatocytes/cytology , Humans , Liver/physiology , Liver Diseases/physiopathology , Liver Failure, Acute/therapy , Models, Biological , Rats , Stem Cells/cytology
12.
Scand J Med Sci Sports ; 18(2): 235-49, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17490454

ABSTRACT

This study investigates how female ice hockey players describe and explain their situation within as well as outside their sport. Information was obtained by semi-structured interviews with female ice hockey players. The results were analyzed in a gender perspective where the main starting point was the concepts of different levels of power relations in society developed by Harding and applied to sports by Kolnes (the symbolic, structural, and individual level). The study shows that the players appeared to share the traditional views of men and women. They also described gender differences in terms of financial and structural conditions as well as differences in ice hockey history. Even though the players described structural inequalities, they were quite content with their situation and the differences in conditions were not considered when they explained the gender differences in ice hockey performance. At the individual level, the players considered themselves different from other women and appeared to share the traditional views of femininity and masculinity. It has been suggested that performance of a sport traditionally associated with the other sex might alter the traditional view of men and women; however, our results lend little support to this suggestion.


Subject(s)
Attitude , Gender Identity , Hockey , Adult , Female , Humans , Interviews as Topic , Sex Factors , Sweden
13.
Am J Transplant ; 7(10): 2326-32, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17845566

ABSTRACT

We conducted a survey of 132 US kidney transplant programs to examine how they evaluate and select potential living kidney donors, focusing on donor-recipient relationships, psychosocial criteria, and consent processes. There is heterogeneity in donor-recipient relationships that are considered acceptable, although most programs (70%) will not consider publicly solicited donors. Most programs (75%) require a psychosocial evaluation for all potential living donors. Most programs agree that knowledge of financial reward (90%), active substance abuse (86%), and active mental health problems (76%) are absolute contraindications to donation. However, there is greater variability in how other psychosocial issues are considered in the selection process. Consent processes are highly variable across programs: donor and recipient consent for the donor evaluation is presumed in 57% and 76% of programs, respectively. The use of 13 different informed consent elements varied from 65% (alternative donation procedures) to 86% (description of evaluation, surgery and recuperative period) of programs. Forty-three percent use a 'cooling off' period. Findings demonstrate high variability in current practice regarding acceptable donor-recipient relationships, psychosocial criteria, and consent processes. Whether greater consensus should be reached on these donor evaluation practices, especially in the context of more expansive use of living donor kidney transplantation, is discussed.


Subject(s)
Informed Consent , Kidney , Living Donors/psychology , Living Donors/statistics & numerical data , Patient Selection , Tissue and Organ Harvesting/methods , Contraindications , Family , Female , Histocompatibility Testing , Humans , Kidney Transplantation/statistics & numerical data , Male , Medical History Taking , Socioeconomic Factors , Tissue and Organ Harvesting/statistics & numerical data , United States
14.
Am J Transplant ; 7(10): 2333-43, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17845567

ABSTRACT

The use of living donors for kidney transplantation in the United States is common, and long-term studies have demonstrated the safety of donation by young, healthy individuals. However, transplant programs have little data to guide them in deciding which donors are unacceptable, and which characteristics are associated with kidney disease or poor psychosocial outcomes after donation. To document current practices in evaluating potential donors, we surveyed all US kidney transplant programs. Compared to a survey 12 years ago, medical criteria for donation are more inclusive in several areas. All responding programs now accept living unrelated donors. Most programs no longer have an upper age limit to be eligible. Programs are now more likely to accept donors with treated hypertension, or a history of kidney stones, provided that certain additional criteria are met. In contrast, medical criteria for donation are more restrictive in other areas, such as younger donor age and low creatinine clearance. Overall, significant variability remains among transplant programs in the criteria used to evaluate donors. These findings highlight the need for more data on long-term outcomes in various types of donors with potential morbidities related to donation.


Subject(s)
Kidney , Living Donors/statistics & numerical data , Patient Selection , Age Distribution , Aged , Cardiovascular Diseases/genetics , Glucose Tolerance Test , Health Surveys , Humans , Middle Aged , Obesity , Patient Care Team , Surveys and Questionnaires , Tissue and Organ Harvesting/methods , United States
15.
Development ; 128(24): 5099-108, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11748145

ABSTRACT

Indian hedgehog (Ihh), one of the three mammalian hedgehog (Hh) proteins, coordinates proliferation and differentiation of chondrocytes during endochondral bone development. Smoothened (Smo) is a transmembrane protein that transduces all Hh signals. In order to discern the direct versus indirect roles of Ihh in cartilage development, we have used the Cre-loxP approach to remove Smo activity specifically in chondrocytes. Animals generated by this means develop shorter long bones when compared to wild-type littermates. In contrast to Ihh mutants (Ihh(n)/Ihh(n)), chondrocyte differentiation proceeds normally. However, like Ihh(n)/Ihh(n) mice, proliferation of chondrocytes is reduced by about 50%, supporting a direct role for Ihh in the regulation of chondrocyte proliferation. Moreover, by overexpressing either Ihh or a constitutively active Smo allele (Smo*) specifically in the cartilage using the bigenic UAS-Gal4 system, we demonstrate that activation of the Ihh signaling pathway is sufficient to promote chondrocyte proliferation. Finally, expression of cyclin D1 is markedly downregulated when either Ihh or Smo activity is removed from chondrocytes, indicating that Ihh regulates chondrocyte proliferation at least in part by modulating the transcription of cyclin D1. Taken together, the present study establishes Ihh as a key mitogen in the endochondral skeleton.


Subject(s)
Bone and Bones/embryology , Cartilage/embryology , Chondrocytes/cytology , Receptors, Cell Surface/metabolism , Receptors, G-Protein-Coupled , Trans-Activators/metabolism , Animals , Bone and Bones/cytology , Cartilage/cytology , Cell Differentiation , Cell Division , Cyclin D1/genetics , Gene Expression Regulation, Developmental , Hedgehog Proteins , Mice , Mice, Knockout , Receptors, Cell Surface/genetics , Signal Transduction , Smoothened Receptor , Tibia/cytology , Tibia/embryology , Trans-Activators/genetics
16.
Development ; 128(22): 4523-34, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11714677

ABSTRACT

During endochondral ossification, two secreted signals, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP), have been shown to form a negative feedback loop regulating the onset of hypertrophic differentiation of chondrocytes. Bone morphogenetic proteins (BMPs), another family of secreted factors regulating bone formation, have been implicated as potential interactors of the Ihh/PTHrP feedback loop. To analyze the relationship between the two signaling pathways, we used an organ culture system for limb explants of mouse and chick embryos. We manipulated chondrocyte differentiation by supplementing these cultures either with BMP2, PTHrP and Sonic hedgehog as activators or with Noggin and cyclopamine as inhibitors of the BMP and Ihh/PTHrP signaling systems. Overexpression of Ihh in the cartilage elements of transgenic mice results in an upregulation of PTHrP expression and a delayed onset of hypertrophic differentiation. Noggin treatment of limbs from these mice did not antagonize the effects of Ihh overexpression. Conversely, the promotion of chondrocyte maturation induced by cyclopamine, which blocks Ihh signaling, could not be rescued with BMP2. Thus BMP signaling does not act as a secondary signal of Ihh to induce PTHrP expression or to delay the onset of hypertrophic differentiation. Similar results were obtained using cultures of chick limbs. We further investigated the role of BMP signaling in regulating proliferation and hypertrophic differentiation of chondrocytes and identified three functions of BMP signaling in this process. First we found that maintaining a normal proliferation rate requires BMP and Ihh signaling acting in parallel. We further identified a role for BMP signaling in modulating the expression of IHH: Finally, the application of Noggin to mouse limb explants resulted in advanced differentiation of terminally hypertrophic cells, implicating BMP signaling in delaying the process of hypertrophic differentiation itself. This role of BMP signaling is independent of the Ihh/PTHrP pathway.


Subject(s)
Bone Morphogenetic Proteins/metabolism , Chondrocytes/cytology , Osteogenesis/physiology , Parathyroid Hormone/metabolism , Proteins/metabolism , Trans-Activators/metabolism , Animals , Cell Differentiation , Cell Division , Chick Embryo , Extremities/embryology , Feedback , Hedgehog Proteins , Hypertrophy , Mice , Mice, Transgenic , Models, Biological , Organ Culture Techniques , Parathyroid Hormone-Related Protein , Signal Transduction , Trans-Activators/genetics
17.
Cancer Epidemiol Biomarkers Prev ; 10(5): 467-73, 2001 May.
Article in English | MEDLINE | ID: mdl-11352856

ABSTRACT

Several studies using families with multiple occurrences of breast cancer have provided evidence for a very high lifetime penetrance in carriers of BRCA1 or BRCA2 mutations. However, there are reasons to suspect that the estimates of penetrance from studies of cancer families may be inflated. Access to the genotypes of incident cases of breast cancer in three hospitals and from a large series of unaffected survey participants provided the basis for direct estimation of the age-specific relative risks attributable to these mutations, and the resulting lifetime penetrance, without any reference to familial aggregation of cancer. Cases were identified from incident series of Jewish patients treated for primary breast cancer at the three hospitals. Control data were obtained from the large series of Jewish women recruited in the Washington, D.C., area by investigators at the National Cancer Institute and limited to 3434 women with no previous history of breast or ovarian cancer. All subjects were genotyped for the three mutations that are relatively common in Ashkenazi Jews, namely 185delAG and 5382 insC in BRCA1 and 6174delT in BRCA2. For BRCA1, the relative risks of breast cancer were estimated to be 21.6 in women under 40 years of age, 9.6 in women 40-49 years of age, and 7.6 in women > or = 50 years of age. On the basis of these estimates, the penetrance of breast cancer at age 70 among BRCA1 mutation carriers is estimated to be 46% (95% confidence, 31%-80%) rising to 59% (95% confidence, 40%-93%) at age 80. For BRCA2, the relative risks in the same three age categories were estimated to be 3.3, 3.3, and 4.6, respectively, resulting in a penetrance at age 70 of 26% (95% confidence, 14%-50%) rising to 38% (95% confidence, 20%-68%) at age 80. The lifetime risk of breast cancer in Jewish women who are mutation carriers estimated via this approach is substantially lower than the reported lifetime risks estimated using multiple-case families. The risks appear to be different for carriers of BRCA1 and BRCA2 mutations.


Subject(s)
Breast Neoplasms/ethnology , Breast Neoplasms/genetics , Genes, BRCA1/genetics , Genetic Predisposition to Disease/ethnology , Heterozygote , Jews/genetics , Adult , Age Distribution , Aged , Case-Control Studies , Female , Genetic Testing , Humans , Incidence , Middle Aged , Mutation , Odds Ratio , Population Surveillance , Probability , Reference Values , Risk Assessment , United States/epidemiology
18.
Clin Oncol (R Coll Radiol) ; 13(1): 38-43, 2001.
Article in English | MEDLINE | ID: mdl-11292134

ABSTRACT

One of the most frequently cited reasons for poor recruitment to multicentre randomized clinical trials is the additional workload placed on clinical staff. We report the effect on patient recruitment of employing a data manager to support clinical staff in an English district general hospital (DGH). In addition, we explore the effect data managers have on the quality of data collected, proxied by the number of queries arising with the trial organizers. We estimate that the cost of employing a data manager on a full-time basis is 502 per patient recruited but may amount to 326 if the appointment is part-time. Data quality is high when full responsibility lies with a data manager but falls when responsibility is shared. Whether the costs of employing a data manager to recruit patients from a DGH are worth incurring depends on the value placed on the speed at which multicentre trials can be completed, how important it is to broaden the research base beyond the traditional setting of teaching hospitals, and the amount of evaluative data required.


Subject(s)
Clinical Trials as Topic , Information Management , Patient Selection , Costs and Cost Analysis , England , Humans , Multicenter Studies as Topic , Research Support as Topic , Salaries and Fringe Benefits , Workforce , Workload
20.
Adv Ren Replace Ther ; 7(4 Suppl 1): S81-4, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11053592

ABSTRACT

Billing data from the Health Care Financing Administration (HCFA) indicated that the influenza immunization rates for dialysis patients in the United States do not meet the goal of 60% set by Healthy People 2000, and fall significantly short of the goal of 90% of all Medicare beneficiaries as outlined in Healthy People 2010. Influenza and pneumonia together are the sixth leading cause of death in the United States. Despite the known benefits of influenza vaccination in reducing morbidity and mortality, only 40% to 50% of high-risk patients are immunized. Although HCFA/Medicare billing data may not provide the best measurement of actual practice, it is currently the only measure available from any national source. The data suggest that there is a need for improvement. Because the HCFA/Medicare rates were based only on those immunizations for which Medicare was billed, End-Stage Renal Disease Network 15 embarked on a project to determine a more accurate rate of immunization within the Network based on information provided by the dialysis facilities. Influenza vaccination rates for the winter 1998 flu season ranged from 51.5% to 84.9% for the states in the Network; the rate for the whole Network was 74.6%. The HCFA/Medicare billed influenza immunization rates were 26.5 to 45.6 percentage points lower.


Subject(s)
Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Arizona , Centers for Medicare and Medicaid Services, U.S. , Colorado , Humans , Immunization/statistics & numerical data , Kidney Failure, Chronic/therapy , Nevada , New Mexico , Total Quality Management , United States , Utah , Wyoming
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