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Sample records for cell disease patients

  1. Pentazocine dependence among sickle cell disease patients ...

    African Journals Online (AJOL)

    Introduction: Sickle cell disease is a chronic disease. Severe bone pain is commonly the hallmark of clinical features. This commonly necessitates the use of analgesics especially Opioids which unfortunately have a high potential to produce dependence. The complications of dependence in patients on any psychoactive ...

  2. Pregnancy Outcome among Patients with Sickle Cell Disease in Jos

    African Journals Online (AJOL)

    Zamzar

    The antenatal complications included anaemia (62.9%), vaso-oclusive. (bone pain) ... Conclusion: Pregnancy in sickle cell disease patients is associated with high maternal and perinatal morbidity .... and malaria (25.7%) were other common.

  3. Addiction or pseudoaddiction in sickle cell disease patients: Time to ...

    African Journals Online (AJOL)

    Objective: The objective of this report is to highlight the background factors associated with opioid abuse among Sickle Cell Disease (SCD) patients. Patients: Eleven patients aged 13-53 years (mean, 26.1yrs) which included six female and five male were seen in the last six year at a tertiary health facility. The modes of ...

  4. Towards safer surgery in patients with sickle cell disease

    International Nuclear Information System (INIS)

    Meshikhes, Abdul-Wahed N.

    2007-01-01

    Surgery in patients with sickle cell disease (SCD) has been associated with high morbidity and mortality. In recent years, a marked improvement in the safety of surgery and anesthesia in this high-risk group of patients has been witnessed; owing to the improvements in surgical and anesthetic care, greater awareness of pathophysiology of disease, proper perioperative preparation and attention to factors predisposing to vasoocclusive crises. However, this is not paralleled by similar improvement in countries where the disease is not prevalent. Greater population mobility in recent years makes recognition of surgical manifestations of the disease and awareness of perioperative management of sickle cell patients undergoing surgical interventions of paramount importance. This article aims to summarize steps towards safer surgery in patients with SCD. (author)

  5. T. B-cell subpopulation in patients with malignant diseases

    International Nuclear Information System (INIS)

    Ogawa, Motoyoshi; Goto, Tatsuhiko; Naruto, Mamiko.

    1978-01-01

    T, B cells in the peripheural blood of patients with malignant diseases were investigated. The percentages of T cells in patients with malignant lymphomas correlated to the extent of disease determined by clinical stagings of Ann Arbor's classification, in stages III and IV T-cells decreased to compare with those in stages I and II, while B-cells did not show any changes. Absolute numbers of lymphocytes, blastogenesis induced by PHA or PWM decreased remarkably during combination chemotherapies and during radiotherapy whereas the percentages of T-cells measuring in the same patients did not influenced consistently by these treatments. The DNA pattern of lymphocytes during treatments was examined by Flow-Microphotometry and the result suggested that those lymphocytes were damaged by treatments and subsequently they were refractory to the action of mitogens. The results indicate that selective timing needs between chemotherapy and immunotherapy. (auth.)

  6. Best practices for transfusion for patients with sickle cell disease

    Science.gov (United States)

    Wun, Ted; Hassell, Kathryn

    2010-01-01

    The β-globin gene mutation in sickle cell anemia results in anemia and repeated bouts of vascular occlusion. The cumulative effect of these vasocclusive events is progressive damage to many organs including the kidneys, lungs, and brain. The transfusion of red blood cells (RBC) can ameliorate many of these complications, but can be associated with both acute and chronic complications, including iron overload. The objective of the Best Practices in Transfusion Medicine for Patients with Sickle Cell Disease (SCD) Conference was to review the available published evidence and clinical experience surrounding the use of RBC transfusions for sickle cell disease by a panel of experts. The expert panel developed explicit clinical guidelines for the use of RBC in SCD patients. The panel also made recommendations for further research. A set of guidelines were produced for dissemination to pertinent stakeholders. If implemented, these clinical pathways have the potential to optimize the use of red blood cell transfusions in SCD.

  7. Red blood cell alloimmunization in sickle cell disease patients in ...

    African Journals Online (AJOL)

    Objective: Alloimmunization is a recognized complication of red blood cell (RBC) transfusion and causes delayed hemolytic transfusion reactions and provides problems sourcing compatible blood for future transfusions. The objective of this study was to determine the frequency of RBC alloimmunization in SCD patients in ...

  8. Modeling neurodegenerative diseases with patient-derived induced pluripotent cells

    DEFF Research Database (Denmark)

    Poon, Anna; Zhang, Yu; Chandrasekaran, Abinaya

    2017-01-01

    patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls generated using CRISPR-Cas9 mediated genome editing. The iPSCs are self-renewable and capable of being differentiated into the cell types affected by the diseases. These in vitro models based on patient-derived iPSCs provide...... the possibilities of generating three-dimensional (3D) models using the iPSCs-derived cells and compare their advantages and disadvantages to conventional two-dimensional (2D) models....

  9. Autopsy findings in sickle cell disease patients in Lagos State ...

    African Journals Online (AJOL)

    Autopsy findings in sickle cell disease patients in Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria. ... The study showed that the most common cause of sudden death was anemia-related (50%) while 21% were due to acute infections, 18.4 % were due to cardiovascular events and 4.6% were due to ...

  10. Tract specific analysis in patients with sickle cell disease

    Science.gov (United States)

    Chai, Yaqiong; Coloigner, Julie; Qu, Xiaoping; Choi, Soyoung; Bush, Adam; Borzage, Matt; Vu, Chau; Lepore, Natasha; Wood, John

    2015-12-01

    Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. It affects numerous people in the world and leads to a shorter life span, pain, anemia, serious infections and neurocognitive decline. Tract-Specific Analysis (TSA) is a statistical method to evaluate white matter alterations due to neurocognitive diseases, using diffusion tensor magnetic resonance images. Here, for the first time, TSA is used to compare 11 major brain white matter (WM) tracts between SCD patients and age-matched healthy subjects. Alterations are found in the corpus callosum (CC), the cortico-spinal tract (CST), inferior fronto-occipital fasciculus (IFO), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinated fasciculus (UNC). Based on previous studies on the neurocognitive functions of these tracts, the significant areas found in this paper might be related to several cognitive impairments and depression, both of which are observed in SCD patients.

  11. Glomerular function in sickle cell disease patients during crisis.

    Science.gov (United States)

    Aderibigbe, A; Arije, A; Akinkugbe, O O

    1994-06-01

    An 8 month prospective study was carried out in 20 adult sickle cell disease (SCD) patients 16 sickle cell anaemia (Hbss) and 4 sickle cell Hbc disease (Hbsc); who had vaso-occlusive crises within the study period to determine the extent of the effect of sickle cell crisis on glomerular function in SCD patients during crisis. The male: female ratio was 1:57 and their mean age was 21.1 +/- 7.9 years. Creatinine clearance (CCr), as an index of glomerular function, was determined at the pre-crisis, crisis, 2 and 4 weeks post-crisis and at the end of the study period. The mean values of their CCr dropped from 113.37 +/- 33.80mls/min at pre-crisis stage to 96.39 +/- 30.13mls/min during crisis (p pre-crisis stage (p > 0.05). It is concluded that glomerular dysfunction in SCD patients during crisis is potentially reversible.

  12. Best practices for transfusion for patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Ted Wun

    2010-01-01

    Full Text Available The beta-globin gene mutation in sickle cell anemia results in anemia and repeated bouts of vascular occlusion. The cumulative effect of these vasocclusive events is progressive damage to many organs including the kidneys, lungs, and brain. The transfusion of red blood cells (RBC can ameliorate many of these complications, but can be associated with both acute and chronic complications, including iron overload. The objective of the Best Practices in Transfusion Medicine for Patients with Sickle Cell Disease (SCD Conference was to review the available published evidence and clinical experience surrounding the use of RBC transfusions for sickle cell disease by a panel of experts. The expert panel developed explicit clinical guidelines for the use of RBC in SCD patients. The panel also made recommendations for further research.  A set of guidelines were produced for dissemination to pertinent stakeholders. If implemented, these clinical pathways have the potential to optimize the use of red blood cell transfusions in SCD.

  13. Increased theta band EEG power in sickle cell disease patients

    Directory of Open Access Journals (Sweden)

    Case M

    2017-12-01

    Full Text Available Michelle Case,1 Sina Shirinpour,1 Huishi Zhang,1 Yvonne H Datta,2 Stephen C Nelson,3 Karim T Sadak,4 Kalpna Gupta,2 Bin He1,5 1Department of Biomedical Engineering, 2Department of Medicine, University of Minnesota, 3Pediatric Hematology-Oncology, Children’s Hospitals and Clinics of Minnesota, 4Pediatric Hematology-Oncology, University of Minnesota Masonic Children’s Hospital, 5Institute for Engineering in Medicine, University of Minnesota, Minneapolis, MN, USA Objective: Pain is a major issue in the care of patients with sickle cell disease (SCD. The mechanisms behind pain and the best way to treat it are not well understood. We studied how electroencephalography (EEG is altered in SCD patients. Methods: We recruited 20 SCD patients and compared their resting state EEG to that of 14 healthy controls. EEG power was found across frequency bands using Welch’s method. Electrophysiological source imaging was assessed for each frequency band using the eLORETA algorithm. Results: SCD patients had increased theta power and decreased beta2 power compared to controls. Source localization revealed that areas of greater theta band activity were in areas related to pain processing. Imaging parameters were significantly correlated to emergency department visits, which indicate disease severity and chronic pain intensity. Conclusion: The present results support the pain mechanism referred to as thalamocortical dysrhythmia. This mechanism causes increased theta power in patients. Significance: Our findings show that EEG can be used to quantitatively evaluate differences between controls and SCD patients. Our results show the potential of EEG to differentiate between different levels of pain in an unbiased setting, where specific frequency bands could be used as biomarkers for chronic pain. Keywords: sickle cell disease, electroencephalography, chronic pain, electrophysiological source imaging, thalamocortical dysrhythmia

  14. Patient Perspectives on Gene Transfer Therapy for Sickle Cell Disease.

    Science.gov (United States)

    Strong, Heather; Mitchell, Monica J; Goldstein-Leever, Alana; Shook, Lisa; Malik, Punam; Crosby, Lori E

    2017-08-01

    Sickle cell disease (SCD) is a chronic genetic disease with high morbidity and early mortality; it affects nearly 100,000 individuals in the USA. Bone marrow transplantation, the only curative treatment, is available to less than 20% of patients because of a number of access barriers. Gene transfer therapy (GTT) has been shown to be curative in animal models and is approved for use in humans for early-phase studies at a few centers. GTT would offer a more accessible treatment option available to all patients. It is important to understand patient perspectives on GTT to help ensure human clinical trial success. Two focus groups were conducted with younger (18-30 years) and older (31 years and older) adults with SCD to obtain data on patient knowledge and beliefs about GTT. Data from these two focus groups was used to develop a GTT educational brochure. A third focus group was conducted to obtain participant feedback on acceptability and feasibility of education and the brochure. Most adults, especially young adults, had little knowledge about GTT and expressed fear and uncertainty about the side effects of chemotherapy (e.g., hair loss, infertility), use of a human immunodeficiency virus (HIV)-derived viral vector, and potential for cancer risk. Participants wanted full transparency in educational materials, but advised researchers not to share the vector's relation to HIV because of cultural stigma and no HIV virus is used for the GTT vector. Older adults had more desire to participate in human clinical GTT trials than younger participants. When recruiting for trials, researchers should develop GTT educational materials that address participant lack of trust in the healthcare system, cultural beliefs, fears related to side effects, and include visual illustrations. Use of such materials will provide adults with SCD the information they need to fully evaluate GTT.

  15. Managing acute complications of sickle cell disease in pediatric patients [digest].

    Science.gov (United States)

    Subramaniam, Sathyaseelan; Chao, Jennifer H; Chaudhari, Pradip

    2016-11-22

    Sickle cell disease is a chronic hematologic disease with a variety of acute, and often recurring, complications. Vaso-occlusive crisis, a unique but common presentation in sickle cell disease, can be challenging to manage. Acute chest syndrome is the leading cause of death in patients with sickle cell disease, occurring in more than half of patients who are hospitalized with a vaso-occlusive crisis. Uncommon diagnoses in children, such as stroke, priapism, and transient red cell aplasia, occur more frequently in patients with sickle cell disease and necessitate a degree of familiarity with the disease process and its management. Patients with sickle cell trait generally have a benign course, but are also subject to serious complications. This issue provides a current review of evidence-based management of the most common acute complications of sickle cell disease seen in pediatric patients in the emergency department. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice].

  16. GVHD (Graft-Versus-Host Disease): A Guide for Patients and Families After Stem Cell Transplant

    Science.gov (United States)

    ... Disease): A guide for patients and families after stem cell transplant The immune system is the body's tool ... and attacking them. When you receive a donor's stem cells (the “graft”), the stem cells recreate the donor's ...

  17. Best practices for transfusion for patients with sickle cell disease

    OpenAIRE

    Ted Wun; Kathryn Hassell

    2010-01-01

    The beta-globin gene mutation in sickle cell anemia results in anemia and repeated bouts of vascular occlusion. The cumulative effect of these vasocclusive events is progressive damage to many organs including the kidneys, lungs, and brain. The transfusion of red blood cells (RBC) can ameliorate many of these complications, but can be associated with both acute and chronic complications, including iron overload. The objective of the Best Practices in Transfusion Medicine for Patients with S...

  18. The role of colonic mast cells and myenteric plexitis in patients with diverticular disease.

    Science.gov (United States)

    Bassotti, Gabrio; Villanacci, Vincenzo; Nascimbeni, Riccardo; Antonelli, Elisabetta; Cadei, Moris; Manenti, Stefania; Lorenzi, Luisa; Titi, Amin; Salerni, Bruno

    2013-02-01

    Gut mast cells represent an important cell population involved in intestinal homeostasis and inflammatory processes. However, their possible role has not to date been investigated in colonic diverticular disease. This study aims to evaluate colonic mast cells in patients undergoing surgery for diverticular disease. Surgical resection samples from 27 patients undergoing surgery for diverticular disease (12 emergency procedures for severe disease and 15 elective procedures) were evaluated. The number of mast cells was assessed in the various layers by means of a specific antibody (tryptase) and compared with those evaluated in ten controls. In patients with mast cells degranulation, double immunohistochemistry, also assessing nerve fibres, was carried out. In addition, the presence of myenteric plexitis was sought. Compared with controls, the number of mast cells in diverticular patients was significantly increased, both as an overall figure and in the various layers of the large bowel. In patients in whom mast cells degranulation was present, these were always closed to nerve fibres. No differences were found between the two subgroups of patients with respect to the number and distribution of mast cells; however, all patients undergoing emergency surgery (but none of those undergoing elective procedures) had myenteric plexitis, represented by lymphocytic infiltration in 67 % and eosinophilic infiltration in 33 % of cases. Patients with diverticular disease display an increase of mast cells in the large bowel. The presence of myenteric plexitis in those with complicated, severe disease, suggest that this could represent a histopathologic marker of more aggressive disease.

  19. Patient-derived stem cells: pathways to drug discovery for brain diseases

    Directory of Open Access Journals (Sweden)

    Alan eMackay-Sim

    2013-03-01

    Full Text Available The concept of drug discovery through stem cell biology is based on technological developments whose genesis is now coincident. The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS. The second is patient-derived stem cells for modelling the cell biology of brain diseases. HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs. HCS combines new fluorescent probes with automated microscopy and computational power to quantify the effects of compounds on cell functions. Stem cell biology has advanced greatly since the discovery of genetic reprogramming of somatic cells into induced pluripotent stem cells (iPSCs. There is now a rush of papers describing their generation from patients with various diseases of the nervous system. Although the majority of these have been genetic diseases, iPSCs have been generated from patients with complex diseases (schizophrenia and sporadic Parkinson’s disease. Some genetic diseases are also modelled in embryonic stem cells generated from blastocysts rejected during in vitro fertilisation. Neural stem cells have been isolated from post-mortem brain of Alzheimer’s patients and neural stem cells generated from biopsies of the olfactory organ of patients is another approach. These olfactory neurosphere-derived cells demonstrate robust disease-specific phenotypes in patients with schizophrenia and Parkinson’s disease. High content screening is already in use to find small molecules for the generation and differentiation of embryonic stem cells and induced pluripotent stem cells. The challenges for using stem cells for drug discovery are to develop robust stem cell culture methods that meet the rigorous requirements for repeatable, consistent quantities of defined cell types at the industrial scale necessary for high

  20. addiction or pseudoaddiction in sickle cell disease patients

    African Journals Online (AJOL)

    2015-06-01

    Jun 1, 2015 ... of its use in the management of pain in this disorder is an issue of debate ... the use of opioid in chronic sickle cell pain and provide alternatives and a suitable guideline .... McCarberg B, Stantos S. Key patient assessment tools and treatment strategies for pain manage- ment. ... R Coll Surg Edinburgh. 1980 ...

  1. Liver Function In Patients With Homozygous Sickle Cell Disease ...

    African Journals Online (AJOL)

    Using the sensitive ELISA technique, 213 patients with sickle cell anemia (112 males and 101 females) aged 6 months to 18 years were screened for Hepatitis B infection using Hepatitis B surface antigen (HBsAg) and antibody to Hepatitis B core antigen. A biochemical evaluation of liver function was carried out on all ...

  2. Hematopoietic stem cell transplantation in sickle cell disease: patient selection and special considerations

    Directory of Open Access Journals (Sweden)

    Bhatia M

    2015-07-01

    Full Text Available Monica Bhatia,1 Sujit Sheth21Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, 2Division of Pediatric Hematology and Oncology, Weill Cornell Medical College, New York, NY, USAAbstract: Hematopoietic stem cell transplantation remains the only curative treatment currently in use for patients with sickle cell disease (SCD. The first successful hematopoietic stem cell transplantation was performed in 1984. To date, approximately 1,200 transplants have been reported. Given the high prevalence of this disorder in Africa, and its emergence in the developed world through immigration, this number is relatively small. There are many reasons for this; primary among them are the availability of a donor, the risks associated with this complex procedure, and the cost and availability of resources in the developing world. Of these, it is fair to say that the risks associated with the procedure have steadily decreased to the point where, if currently performed in a center with experience using a matched sibling donor, overall survival is close to 100% and event-free survival is over 90%. While there is little controversy around offering hematopoietic stem cell transplantation to symptomatic SCD patients with a matched sibling donor, there is much debate surrounding the use of this modality in “less severe” patients. An overview of the current state of our understanding of the pathology and treatment of SCD is important to show that our current strategy is not having the desired impact on survival of homozygous SCD patients, and should be changed to significantly impact the small proportion of these patients who have matched siblings and could be cured, especially those without overt clinical manifestations. Both patient families and providers must be made to understand the progressive nature of SCD, and should be encouraged to screen full siblings of patients with homozygous SCD for their potential to

  3. Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease

    OpenAIRE

    Shroff, Geeta

    2016-01-01

    Case series Patient: Male, 42 ? Female, 30 Final Diagnosis: Human embryonic stem cells showed good therapeutic potential for treatment of multiple sclerosis with lyme disease Symptoms: Fatigue ? weakness in limbs Medication: ? Clinical Procedure: Human embryonic stem cells transplantation Specialty: Transplantology Objective: Rare disease Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause dela...

  4. Histamine release from gut mast cells from patients with inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Nolte, Hendrik; Spjeldnæs, Nikolaj; Kruse, Aksel

    1990-01-01

    Inflammatory mediators from intestinal mast cells may serve as initiators of acute and delayed inflammation. Mast cell histamine release was measured in 19 patients with inflammatory bowel diseases using gut mast cells from enzymatically dispersed endoscopic forceps biopsy specimens...... of macroscopically inflamed and normal tissue. Mast cells and corresponding basophils were challenged with anti-IgE, anti-IgG, subclass anti-IgG4, and formyl-methionyl-leucyl-phenylalanine (FMLP) and results were compared with those from nine patient control subjects. The mast cell count in patients with ulcerative...... colitis was increased compared with that in control subjects and patients with Crohn's disease, and the mast cell count obtained from inflamed tissue was greater than that of normal tissue. The study also shows the heterogeneity of the responsiveness of the histamine releasing cells to various...

  5. Changing practice: red blood cell typing by molecular methods for patients with sickle cell disease.

    Science.gov (United States)

    Casas, Jessica; Friedman, David F; Jackson, Tannoa; Vege, Sunitha; Westhoff, Connie M; Chou, Stella T

    2015-06-01

    Extended red blood cell (RBC) antigen matching is recommended to limit alloimmunization in patients with sickle cell disease (SCD). DNA-based testing to predict blood group phenotypes has enhanced availability of antigen-negative donor units and improved typing of transfused patients, but replacement of routine serologic typing for non-ABO antigens with molecular typing for patients has not been reported. This study compared the historical RBC antigen phenotypes obtained by hemagglutination methods with genotype predictions in 494 patients with SCD. For discrepant results, repeat serologic testing was performed and/or investigated by gene sequencing for silent or variant alleles. Seventy-one typing discrepancies were identified among 6360 antigen comparisons (1.1%). New specimens for repeat serologic testing were obtained for 66 discrepancies and retyping agreed with the genotype in 64 cases. One repeat Jk(b-) serologic phenotype, predicted Jk(b+) by genotype, was found by direct sequencing of JK to be a silenced allele, and one N typing discrepancy remains under investigation. Fifteen false-negative serologic results were associated with alleles encoding weak antigens or single-dose Fy(b) expression. DNA-based RBC typing provided improved accuracy and expanded information on RBC antigens compared to hemagglutination methods, leading to its implementation as the primary method for extended RBC typing for patients with SCD at our institution. © 2015 AABB.

  6. Enteric Neural Cells From Hirschsprung Disease Patients Form Ganglia in Autologous Aneuronal ColonSummary

    Directory of Open Access Journals (Sweden)

    Benjamin N. Rollo

    2016-01-01

    Full Text Available Background & Aims: Hirschsprung disease (HSCR is caused by failure of cells derived from the neural crest (NC to colonize the distal bowel in early embryogenesis, resulting in absence of the enteric nervous system (ENS and failure of intestinal transit postnatally. Treatment is by distal bowel resection, but neural cell replacement may be an alternative. We tested whether aneuronal (aganglionic colon tissue from patients may be colonized by autologous ENS-derived cells. Methods: Cells were obtained and cryopreserved from 31 HSCR patients from the proximal resection margin of colon, and ENS cells were isolated using flow cytometry for the NC marker p75 (nine patients. Aneuronal colon tissue was obtained from the distal resection margin (23 patients. ENS cells were assessed for NC markers immunohistologically and by quantitative reverse-transcription polymerase chain reaction, and mitosis was detected by ethynyl-2′-deoxyuridine labeling. The ability of human HSCR postnatal ENS-derived cells to colonize the embryonic intestine was demonstrated by organ coculture with avian embryo gut, and the ability of human postnatal HSCR aneuronal colon muscle to support ENS formation was tested by organ coculture with embryonic mouse ENS cells. Finally, the ability of HSCR patient ENS cells to colonize autologous aneuronal colon muscle tissue was assessed. Results: ENS-derived p75-sorted cells from patients expressed multiple NC progenitor and differentiation markers and proliferated in culture under conditions simulating Wnt signaling. In organ culture, patient ENS cells migrated appropriately in aneural quail embryo gut, and mouse embryo ENS cells rapidly spread, differentiated, and extended axons in patient aneuronal colon muscle tissue. Postnatal ENS cells derived from HSCR patients colonized autologous aneuronal colon tissue in cocultures, proliferating and differentiating as neurons and glia. Conclusions: NC-lineage cells can be obtained from HSCR patient

  7. Lactate dehydrogenase as a biomarker for early renal damage in patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Mohammad S Alzahri

    2015-01-01

    Full Text Available Among many complications of sickle cell disease, renal failure is the main contributor to early mortality. It is present in up to 21% of patients with sickle cell disease. Although screening for microalbuminuria and proteinuria is the current acceptable practice to detect and follow renal damage in patients with sickle cell disease, there is a crucial need for other, more sensitive biomarkers. This becomes especially true knowing that those biomarkers start to appear only after more than 60% of the kidney function is lost. The primary purpose of this study is to determine whether lactate dehydrogenase (LDH correlates with other, direct and indirect bio-markers of renal insufficiency in patients with sickle cell disease and, therefore, could be used as a biomarker for early renal damage in patients with sickle cell disease. Fifty-five patients with an established diagnosis of sickle cell disease were recruited to in the study. Blood samples were taken and 24-h urine collection samples were collected. Using Statcrunch, a data analysis tool available on the web, we studied the correlation between LDH and other biomarkers of kidney function as well as the distribution and relationship between the variables. Regression analysis showed a significant negative correlation between serum LDH and creatinine clearance, R (correlation coefficient = -0.44, P = 0.0008. This correlation was more significant at younger age. This study shows that in sickle cell patients LDH correlates with creatinine clearance and, therefore, LDH could serve as a biomarker to predict renal insufficiency in those patients.

  8. thirst perception in dehydrated sickle cell disease patients in steady

    African Journals Online (AJOL)

    Daniel Owu

    Ingram, 1956). It is prevalent especially among people with ancestry in ..... thalassemia and sickle polymerization tendency on the urine concentrating defect of individual with sickle cell trait. J. Clin. Invest., 88: 1963-. 1968. Igbokwe, VU. and Obika ...

  9. Low bone mass density is associated with hemolysis in brazilian patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Gabriel Baldanzi

    2011-01-01

    Full Text Available OBJECTIVES: To determine whether kidney disease and hemolysis are associated with bone mass density in a population of adult Brazilian patients with sickle cell disease. INTRODUCTION: Bone involvement is a frequent clinical manifestation of sickle cell disease, and it has multiple causes; however, there are few consistent clinical associations between bone involvement and sickle cell disease. METHODS: Patients over 20 years of age with sickle cell disease who were regularly followed at the Hematology and Hemotherapy Center of Campinas, Brazil, were sorted into three groups, including those with normal bone mass density, those with osteopenia, and those with osteoporosis, according to the World Health Organization criteria. The clinical data of the patients were compared using statistical analyses. RESULTS: In total, 65 patients were included in this study: 12 (18.5% with normal bone mass density, 37 (57% with osteopenia and 16 (24.5% with osteoporosis. Overall, 53 patients (81.5% had bone mass densities below normal standards. Osteopenia and osteoporosis patients had increased lactate dehydrogenase levels and reticulocyte counts compared to patients with normal bone mass density (p<0.05. Osteoporosis patients also had decreased hemoglobin levels (p<0.05. Hemolysis was significantly increased in patients with osteoporosis compared with patients with osteopenia, as indicated by increased lactate dehydrogenase levels and reticulocyte counts as well as decreased hemoglobin levels. Osteoporosis patients were older, with lower glomerular filtration rates than patients with osteopenia. There was no significant difference between the groups with regard to gender, body mass index, serum creatinine levels, estimated creatinine clearance, or microalbuminuria. CONCLUSION: A high prevalence of reduced bone mass density that was associated with hemolysis was found in this population, as indicated by the high lactate dehydrogenase levels, increased

  10. Cytotoxic T cells are preferentially activated in the duodenal epithelium from patients with florid coeliac disease.

    Science.gov (United States)

    Buri, Caroline; Burri, Philipp; Bähler, Peter; Straumann, Alex; Müller-Schenker, Beatrice; Birrer, Stefan; Mueller, Christoph

    2005-06-01

    Villous atrophy and increased numbers of intraepithelial T cells in duodenal biopsies represent a hallmark of coeliac disease. In the present study, an attempt has been made to define whether cytotoxic cell subsets are activated in situ in the affected mucosa of susceptible individuals early after ingestion of a gluten-containing diet. Duodenal biopsies from 11 patients with coeliac disease who repeatedly underwent endoscopic biopsy after ingestion of individually dosed amounts of gluten were used for immunohistochemistry and in situ hybridization. To identify the cell subsets expressing perforin mRNA and protein, in situ hybridization and FACS analyses were performed on cells isolated from fresh biopsies. Compared with normal mucosa, the number of intraepithelial lymphocytes containing perforin mRNA and protein increased significantly in tissue samples showing moderate or florid coeliac disease and closely paralleled the severity of morphological alteration, whereas the frequency of perforin-expressing lamina propria lymphocytes increased only moderately. Cells isolated from florid biopsies that expressed perforin mRNA and protein were preferentially T-cell receptor (TCR) alphabeta T cells. The increase in both the absolute number and the percentage of lymphocytes expressing perforin mRNA indicates in situ activation of lymphocytes within the epithelial compartment in florid coeliac disease upon ingestion of a gluten-containing diet in patients predisposed to coeliac disease. Copyright 2005 Pathological Society of Great Britain and Ireland

  11. Interleukin 8 as a vaso-occlusive marker in Brazilian patients with sickle cell disease.

    Science.gov (United States)

    Gonçalves, M S; Queiroz, I L; Cardoso, S A; Zanetti, A; Strapazoni, A C; Adorno, E; Albuquerque, A; Sant'Ana, A; dos Reis, M G; Barral, A; Barral Netto, M

    2001-10-01

    Sickle cell disease has a worldwide distribution and is a public health problem in Brazil. Although vaso-occlusive crisis (VOC) is one of the most important clinical features of the disease, there are still several steps of its pathogenesis which are unknown. The increase of the chemotactic factor interleukin 8 (IL-8) has been reported to be involved in sickle cell disease crisis, but this has not been demonstrated conclusively. In the present study we analyzed serum IL-8 levels by ELISA and hematological parameters and hemoglobin patterns by standard techniques in 23 (21 SS and 2 SC) Brazilian patients with sickle cell syndromes during VOC caused by different inducing factors, 22 (21 SS and 1 SC) sickle cell patients out of crisis, and 11 healthy controls. Increased IL-8 levels were observed in 19 of 23 VOC patients (79.2%), 3 of them with more than 1,000 pg/ml. Seventeen of 22 (77.3%) non-crisis patients showed low IL-8 levels (less than 15 pg/ml). Healthy controls had low IL-8 levels. A significant difference in serum IL-8 levels was observed between crisis and non-crisis sickle cell patients (Pcrisis-inducing factor. We conclude that in the studied population, IL-8 concentration may be a useful VOC marker, although the mechanism of the pathogenic process of sickle cell VOC syndromes remains unclear.

  12. Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease.

    Science.gov (United States)

    Shroff, Geeta

    2016-12-13

    BACKGROUND Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. CASE REPORT Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD. The hESCs were administered via different routes including intramuscular, intravenous, and supplemental routes (e.g., deep spinal, caudal, intercostal through eye drops) to regenerate the injured cells. Both the patients showed remarkable improvement in their functional skills, overall stamina, cognitive abilities, and muscle strength. Furthermore, the improvement in the patients' conditions were assessed by magnetic resonance tractography and single photon emission computed tomography (SPECT). CONCLUSIONS Therapy with hESCs might emerge as an effective and safe treatment for patients with both MS and LD. Well-designed clinical trials and follow-up studies are needed to prove the long-term efficacy and safety of hESC therapy in the treatment of patients with MS and LD.

  13. Modeling neurodegenerative diseases with patient-derived induced pluripotent cells: Possibilities and challenges.

    Science.gov (United States)

    Poon, Anna; Zhang, Yu; Chandrasekaran, Abinaya; Phanthong, Phetcharat; Schmid, Benjamin; Nielsen, Troels T; Freude, Kristine K

    2017-10-25

    The rising prevalence of progressive neurodegenerative diseases coupled with increasing longevity poses an economic burden at individual and societal levels. There is currently no effective cure for the majority of neurodegenerative diseases and disease-affected tissues from patients have been difficult to obtain for research and drug discovery in pre-clinical settings. While the use of animal models has contributed invaluable mechanistic insights and potential therapeutic targets, the translational value of animal models could be further enhanced when combined with in vitro models derived from patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls generated using CRISPR-Cas9 mediated genome editing. The iPSCs are self-renewable and capable of being differentiated into the cell types affected by the diseases. These in vitro models based on patient-derived iPSCs provide the opportunity to model disease development, uncover novel mechanisms and test potential therapeutics. Here we review findings from iPSC-based modeling of selected neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and spinocerebellar ataxia. Furthermore, we discuss the possibilities of generating three-dimensional (3D) models using the iPSCs-derived cells and compare their advantages and disadvantages to conventional two-dimensional (2D) models. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Expression of a retinoic acid signature in circulating CD34 cells from coronary artery disease patients

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    van der Laan Anja M

    2010-06-01

    Full Text Available Abstract Background Circulating CD34+ progenitor cells have the potential to differentiate into a variety of cells, including endothelial cells. Knowledge is still scarce about the transcriptional programs used by CD34+ cells from peripheral blood, and how these are affected in coronary artery disease (CAD patients. Results We performed a whole genome transcriptome analysis of CD34+ cells, CD4+ T cells, CD14+ monocytes, and macrophages from 12 patients with CAD and 11 matched controls. CD34+ cells, compared to other mononuclear cells from the same individuals, showed high levels of KRAB box transcription factors, known to be involved in gene silencing. This correlated with high expression levels in CD34+ cells for the progenitor markers HOXA5 and HOXA9, which are known to control expression of KRAB factor genes. The comparison of expression profiles of CD34+ cells from CAD patients and controls revealed a less naïve phenotype in patients' CD34+ cells, with increased expression of genes from the Mitogen Activated Kinase network and a lowered expression of a panel of histone genes, reaching levels comparable to that in more differentiated circulating cells. Furthermore, we observed a reduced expression of several genes involved in CXCR4-signaling and migration to SDF1/CXCL12. Conclusions The altered gene expression profile of CD34+ cells in CAD patients was related to activation/differentiation by a retinoic acid-induced differentiation program. These results suggest that circulating CD34+ cells in CAD patients are programmed by retinoic acid, leading to a reduced capacity to migrate to ischemic tissues.

  15. disease patient

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    Setareh Mamishi

    2016-09-01

    Full Text Available Background and Purpose: Chronic granulomatous disease (CGD is an inherited disorder of the nicotinamide adenine dinucleotide phosphate (NADPH oxidase complex. This disorder results in recurrent life-threatening bacterial and fungal infections. Aspergillus species are the most common fungal infections in these patients. Case Report: Herein, we present a case of fungal infection in a girl with CGD. We confirmed aspergillosis through the positive microscopic and macroscopic examinations, as well as radiology results. Invasive aspergillosis in this patient with pneumonia, lung abscess, and osteomyelitis of the ribs was not initially treated with amphotericin B (Am B and recombinant interferon-gamma. Conclusion: Among infectious diseases, fungal infections, in particular aspergillosis, remain a serious problem in CGD patients. Considering poor clinical response and deficient immune system, rapid diagnosis of fungal infection and optimizing the treatment of these patients are recommended.

  16. T regulatory cells are markers of disease activity in multiple sclerosis patients.

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    Dacia Dalla Libera

    Full Text Available FoxP3⁺ Treg cells are believed to play a role in the occurrence of autoimmunity and in the determination of clinical recurrences. Contradictory reports are, however, available describing frequency and function of Treg cells during autoimmune diseases. We examined, by both polychromatic flow cytometry, and real-time RT-PCR, several Treg markers in peripheral blood mononuclear cells from patients with multiple sclerosis (MS, an autoimmune disease affecting the central nervous system. We found that Tregs, as defined by CD25, CD39, FoxP3, CTLA4, and GITR expression, were significantly decreased in stable MS patients as compared to healthy donors, but, surprisingly, restored to normal levels during an acute clinical attack. We conclude that Treg cells are not involved in causing clinical relapses, but rather react to inflammation in the attempt to restore homeostasis.

  17. ABO (H) secretor status of sickle cell disease patients in Zaria ...

    African Journals Online (AJOL)

    Certain individuals secrete ABO blood group antigens in body fluids and secretions while others do not. In this study, the presence of water soluble agglutinogens in body fluids such as blood, saliva and urine of 64 sickle cell disease patients and 75 AA genotype subjects who served as control were taken and tested by ...

  18. Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease

    NARCIS (Netherlands)

    Krenning, Guido; Dankers, Patricia Y. W.; Drouven, Johannes W.; Waanders, Femke; Franssen, Casper F. M.; van Luyn, Marja J. A.; Harmsen, Martin C.; Popa, Eliane R.

    Krenning G, Dankers PY, Drouven JW, Waanders F, Franssen CF, van Luyn MJ, Harmsen MC, Popa ER. Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease. Am J Physiol Renal Physiol 296: F1314-F1322, 2009. First published April 1, 2009; doi:

  19. Mortality rate in Sickle Cell Disease Patients in Crisis at a ...

    African Journals Online (AJOL)

    The Haematology Day Care Unit (HDCU) of the University College Hospital, Ibadan, Nigeria was established in 1975 with the main goal of providing immediate and specialized care to haematological emergencies, particularly sickle cell disease (SCD) patients. Since inception, a systematic analysis of its effectiveness has ...

  20. Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease.

    Science.gov (United States)

    Powell, Tiffany M; Paul, Jonathan D; Hill, Jonathan M; Thompson, Michael; Benjamin, Moshe; Rodrigo, Maria; McCoy, J Philip; Read, Elizabeth J; Khuu, Hanh M; Leitman, Susan F; Finkel, Toren; Cannon, Richard O

    2005-02-01

    Endothelial progenitor cells (EPCs) that may repair vascular injury are reduced in patients with coronary artery disease (CAD). We reasoned that EPC number and function may be increased by granulocyte colony-stimulating factor (G-CSF) used to mobilize hematopoietic progenitor cells in healthy donors. Sixteen CAD patients had reduced CD34(+)/CD133(+) (0.0224+/-0.0063% versus 0.121+/-0.038% mononuclear cells [MNCs], P<0.01) and CD133(+)/VEGFR-2(+) cells, consistent with EPC phenotype (0.00033+/-0.00015% versus 0.0017+/-0.0006% MNCs, P<0.01), compared with 7 healthy controls. Patients also had fewer clusters of cells in culture, with out-growth consistent with mature endothelial phenotype (2+/-1/well) compared with 16 healthy subjects at high risk (13+/-4/well, P<0.05) or 14 at low risk (22+/-3/well, P<0.001) for CAD. G-CSF 10 microg/kg per day for 5 days increased CD34(+)/CD133(+) cells from 0.5+/-0.2/microL to 59.5+/-10.6/microL and CD133(+)/ VEGFR-2(+) cells from 0.007+/-0.004/microL to 1.9+/-0.6/microL (both P<0.001). Also increased were CD133(+) cells that coexpressed the homing receptor CXCR4 (30.4+/-8.3/microL, P<0.05). Endothelial cell-forming clusters in 10 patients increased to 27+/-9/well after treatment (P<0.05), with a decline to 9+/-4/well at 2 weeks (P=0.06). Despite reduced EPCs compared with healthy controls, patients with CAD respond to G-CSF with increases in EPC number and homing receptor expression in the circulation and endothelial out-growth in culture. Endothelial progenitor cells (EPCs) are reduced in coronary artery disease. Granulocyte colony-stimulating factor (CSF) administered to patients increased: (1) CD133+/VEGFR-2+ cells consistent with EPC phenotype; (2) CD133+ cells coexpressing the chemokine receptor CXCR4, important for homing of EPCs to ischemic tissue; and (3) endothelial cell-forming clusters in culture. Whether EPCs mobilized into the circulation will be useful for the purpose of initiating vascular growth and myocyte repair

  1. Pain measurement as part of primary healthcare of adult patients with sickle cell disease

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    Andreza Aparecida Felix Signorelli

    2013-01-01

    Full Text Available OBJECTIVE: The aim of this exploratory, cross-sectional study was to evaluate pain in sickle cell disease patients and aspects related to primary healthcare. METHODS: Data were obtained through home interviews. The assessment instruments (body diagram, Numerical Pain Scale, McGill Pain Questionnaire collected information on the underlying disease and on pain. Data were analyzed using the Statistical Package for Social Sciences program for Windows. Associations between the subgroups of sickle cell disease patients (hemoglobin SS, hemoglobin SC, sickle β-thalassemia and others and pain were analyzed using contingency tables and non-parametric tests of association (classic chi-square, Fisher's and Kruskal-Wallis with a level of 5% (p-value < 0.05 being set for the rejection of the null hypothesis. RESULTS: Forty-seven over 18-year-old patients with sickle cell disease were evaluated. Most were black (78.7% and female (59.6% and the mean age was 30.1 years. The average number of bouts of pain annually was 7.02; pain was predominantly reported by individuals with sickle cell anemia (hemoglobin SS. The intensity of pain (Numeric Pain Scale was 5.5 and the quantitative index (McGill was 35.9. This study also shows that patients presented a high frequency of moderately painful crises in their own homes. CONCLUSION: According to these facts, it is essential that pain related to sickle cell disease is properly identified, quantified, characterized and treated at the three levels of healthcare. In primary healthcare, accurate measurement of pain combined with better care may decrease acute painful episodes and consequently minimize tissue damage, thus improving the patient's overall health.

  2. Challenges and opportunities for stem cell therapy in patients with chronic kidney disease.

    Science.gov (United States)

    Hickson, LaTonya J; Eirin, Alfonso; Lerman, Lilach O

    2016-04-01

    Chronic kidney disease (CKD) is a global health care burden affecting billions of individuals worldwide. The kidney has limited regenerative capacity from chronic insults, and for the most common causes of CKD, no effective treatment exists to prevent progression to end-stage kidney failure. Therefore, novel interventions, such as regenerative cell-based therapies, need to be developed for CKD. Given the risk of allosensitization, autologous transplantation of cells to boost regenerative potential is preferred. Therefore, verification of cell function and vitality in CKD patients is imperative. Two cell types have been most commonly applied in regenerative medicine. Endothelial progenitor cells contribute to neovasculogenesis primarily through paracrine angiogenic activity and partly by differentiation into mature endothelial cells in situ. Mesenchymal stem cells also exert paracrine effects, including proangiogenic, anti-inflammatory, and antifibrotic activity. However, in CKD, multiple factors may contribute to reduced cell function, including older age, coexisting cardiovascular disease, diabetes, chronic inflammatory states, and uremia, which may limit the effectiveness of an autologous cell-based therapy approach. This Review highlights current knowledge on stem and progenitor cell function and vitality, aspects of the uremic milieu that may serve as a barrier to therapy, and novel methods to improve stem cell function for potential transplantation. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  3. Quality of life in patients with sickle cell disease in Jamaica: rural-urban differences.

    Science.gov (United States)

    Asnani, Monika R; Reid, Marvin E; Ali, Susanna B; Lipps, Garth; Williams-Green, Pauline

    2008-01-01

    Quality of life (QOL) refers to people's ability to function in the ordinary tasks of living. It moves beyond direct manifestations of illness to the patient's personal morbidity. These assessments are an important aspect of chronic disease management. Sickle cell disease (SCD) is a chronic and potentially, quite a debilitating disease. The disease is severe and may result in significant morbidity, as well as a shortened life span. It is the most common genetic disorder seen in Jamaica and impacts on physical, psychological, social and occupational wellbeing. Jamaica is a developing country where support systems that exist for patients with SCD are sparse. Health related QOL has been shown to be poorer in people living in the rural areas as compared with urban populations. Utilization of comprehensive sickle cells disease services has also been shown to be lower for individuals with the disease living in rural areas than for those living in urban areas. As there are rural-urban differences in Jamaica's health services, it is hypothesized that there may be rural-urban differences in the experiences of the disease and the QOL of these patients in these subgroups. The SF 36 v2 (Short Form 36) questionnaire has been validated for use in the Jamaican SCD population. This validated questionnaire was interviewer-administered to 166 patients presenting to an urban clinic for routine health maintenance visits and to 90 patients presenting to the rural clinics for routine visits. Socio-demographic information was also collected on these two groups. Multiple linear regression analyses were performed to study predictors of QOL in these two sub-populations. The study received ethical approval from the University of the West Indies/University Hospital of the West Indies Ethics Committee. There were no significant differences in the measured socio-demographic characteristics of the rural and urban patients. Living in rural areas compared with urban areas (p <0.001), being

  4. Pain control in sickle cell disease patients: use of complementary and alternative medicine.

    Science.gov (United States)

    Thompson, Wendy E; Eriator, Ike

    2014-02-01

    To examine the factors associated with the use of complementary and alternative medicine (CAM) as reported by patients attending an adult sickle cell clinic at a tertiary institution. Cross-sectional survey. This study was conducted in a university tertiary care adult sickle cell clinic. Adult sickle cell patients. Following Institutional Review Board approval, a questionnaire was administered to patients in a sickle cell clinic to examine their use of CAM for managing pain at home and while admitted to the hospital. Of the 227 respondents who completed the questionnaire, 92% experienced pain lasting from 6 months to more than 2 years. Two hundred and eight (91.6%) indicated that they have used CAM within the last 6 months to control pain. The frequency of CAMs use was higher among females, singles, those with more education, and higher household income. This study shows that a substantial majority of sickle cell patients live with pain on a regular basis and that there is substantial CAM use in the adult Sickle cell disease population. Being female and having a high school or higher education were significantly correlated with the use of CAM in sickle cell patients. A variety of CAM therapies are used, with the most common being prayer. Wiley Periodicals, Inc.

  5. [Th17 and Treg cell levels in patients with sarcoidosis and their relation to disease activation].

    Science.gov (United States)

    Weng, Yue-song; Wang, Hua-ying; Lv, Ding-feng; Fu, Zhong-ming; Yu, Wan-jun

    2015-03-01

    To investigate the Th17 cell and Treg cell levels in patients with sarcoidosis, and their relation to disease activation and glucocorticoids treatment. Twenty-three sarcoidosis patients admitted in Yinzhou People's Hospital from January 2009 to December 2013 and 25 healthy subjects (controls) were included in this study. The blood samples and bronchoalveolar lavage fluid (BALF) samples were collected in all patients before and after glucocorticoids treatment. The serum angiotensin converting enzyme (SACE) levels were detected. The percentages of Th17 cells and Treg cells in peripheral blood and BALF were determined by flow cytometry, the concentrations of cytokines in serum and supernatants of BALF were measured by enzyme-linked immunosorbent assay (ELISA). The levels of ROR-γt and Foxp3 mRNA transcripts in peripheral blood mononuclear cells (PBMC) were determined by real-time quantitative PCR. The potential correlation between the percentages of Th17 or Treg cells and SACE levels was evaluated. Compared with healthy controls, significantly higher frequencies of Th17 cells (4.34%±0.89% vs 1.60% ± 0.42%), lower frequencies of Treg cells (1.28% ± 0.37% vs 3.39% ± 0.50%) in peripheral blood were observed. Higher level of ROR-γt mRNA (21.31 ± 3.55 vs 3.63 ± 1.00) and lower level of Foxp3 mRNA (1.60 ± 0.24 vs 3.12 ± 0.76) in peripheral blood were detected in sarcoidosis patients in active stage (before glucocorticoids treatment) (all PSACE (r= 0.781). The imbalance of Th17 cells and Treg cells in peripheral blood and airway may be involved in the pathogenesis of sarcoidosis, which was associated with the activity of disease, and the treatment of glucocorticoids may achieve a therapeutic effect by correcting the immune imbalance.

  6. The composition of T cell subtypes in duodenal biopsies are altered in coeliac disease patients.

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    Janni V Steenholt

    Full Text Available One of the hallmarks of Celiac disease (CD is intraepithelial lymphocytosis in the small intestine. Until now, investigations to characterize the T cell subpopulations within the epithelial layer have not discriminated between the heterodimeric co-receptor molecule, CD8αβ, and the possibly immunoregulatory CD8αα homodimer molecule. Besides TCRαβ+ CD4+ cells, no other phenotypes have been shown to be gluten-reactive. Using flow cytometry on lymphocytes from duodenal biopsies, we determined that the number of B cells (CD3- CD19+ and the number of CD3+ CD4- CD8- double-negative (DN T cells were elevated 6-7 fold in children with CD. We next isolated and quantified intraepithelial lymphocytes (IELs from biopsies obtained from patients (both children and adults with CD, potential CD and non-CD controls. Flow cytometric analysis of the duodenal T cell subpopulations was performed including the markers TCRαβ, TCRγδ, CD4, CD8α and CD8β. Proportions of γδ T cells and CD8αβ+ cells among IELs were increased in CD patients, whereas proportions of CD4+ CD8αα+ and CD4+ single-positive T cells were decreased. Additionally, two gluten-reactive T cell lines (TCLs derived from CD biopsies were analyzed for changes in proportions of T cell subsets before and after gluten stimulation. In a proliferation assay, dividing cells were tracked with carboxyfluorescein succinimidyl ester (CFSE, and both αβ and γδ T cells proliferated in response to gluten. Changes in duodenal T cell subpopulations in potential CD patients followed the same pattern as for CD patients, but with less pronounced effect.

  7. The Effectiveness of self management program on quality of life in patients with sickle cell disease

    Science.gov (United States)

    Ahmadi, M; Jahani, S; Poormansouri, S; Shariati, A; Tabesh, H

    2015-01-01

    Background Sickle cell patients suffer from many physical, psychological, and social problems that can affect their quality of life. To deal with this chronic condition and manage their disease and prevent complications associated with the disease, they must learn skills and behaviours. The aim of this study was to determine the effectiveness of self-management programs on quality of life in these patients. Material and Methods Samples of this quasi-experimental study, which included 69 patients with sickle cell disease referring to the Thalassemia Clinic of Shafa Hospital, were entered into the study by census method. Patients received a self-management program using the 5A model for 12 weeks, while their quality of life before the intervention were assessed at the twelfth week and thirty-sixth week using SF-36 questionnaire. Data were analyzed by descriptive statistics, paired t-test, Wilcoxon test, Hotelling's T2, and repeated measures test. Results The eight dimensions and the total QoL score after intervention were significantly increased compared to those before the intervention (P<0.001). Repeated measures test showed that the mean score of eight QoL dimensions and the total QoL score decreased in the thirty-sixth week, compared to twelfth week. However, it was significantly enhanced in comparison with the intervention baseline (P<0.05). Conclusions Current study revealed the efficacy of self-management interventions on the quality of life in patients with sickle cell disease. Therefore, application of this supportive method could be useful to empower the patients and help them to manage the disease. PMID:25914799

  8. Treatment with adipose stem cells in a patient with moderate Alzheimer's disease: case report

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    Tsolaki M

    2015-10-01

    Full Text Available Magda Tsolaki,1,2 Stelios Zygouris,1,3 Vassilis Tsoutsikas,2 Doxakis Anestakis,2,4,5 George Koliakos6,7 1Third Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Greek Association of Alzheimer's Disease and Related Disorders, Thessaloniki, Greece; 3CND+, 4Laboratory of Forensic Medicine and Toxicology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece; 5Laboratory of General Biology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece; 6Biohellenika Stem Cells Bank, Thessaloniki, Greece; 7Department of Biological Chemistry, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece Objective: This article presents the case of a female patient with Alzheimer's disease (AD. The patient was treated with cholinesterase inhibitors and also with intravenous administration of autologous adipose stem cells.Methods: The patient was assessed with a neuropsychological battery including measures of general cognition, functional problems, neuropsychiatric issues, memory (verbal, visual and episodic, verbal learning and visuospatial abilities. Magnetic resonance imaging (MRI scans were conducted before and after the treatment with stem cells.Results: A transient and mild improvement of scores in measures of general cognition and neuropsychiatric issues was evident. A rapid deterioration followed the initial improvement. The first MRI scan showed ischemic areas in periventricular white matter of both hemispheres, as well as in both temporal and parietal lobes. The second MRI scan revealed the same picture with no significant changes.Conclusion: This case report indicates that the administration of stem cells is feasible in a clinical setting however its effectiveness in the treatment of AD is uncertain. The improvement of the patient's condition highlights the potential therapeutic action of stem cells, however the rapid deterioration poses

  9. Partial Red Blood Cell Exchange in Children and Young Patients with Sickle Cell Disease: Manual Versus Automated Procedure.

    Science.gov (United States)

    Escobar, Carlos; Moniz, Marta; Nunes, Pedro; Abadesso, Clara; Ferreira, Teresa; Barra, António; Lichtner, Anabela; Loureiro, Helena; Dias, Alexandra; Almeida, Helena

    2017-10-31

    The benefits of manual versus automated red blood cell exchange have rarely been documented and studies in young sickle cell disease patients are scarce. We aim to describe and compare our experience in these two procedures. Young patients (≤ 21 years old) who underwent manual- or automated-red blood cell exchange for prevention or treatment of sickle cell disease complications were included. Clinical, technical and hematological data were prospectively recorded and analyzed. Ninety-four red blood cell exchange sessions were performed over a period of 68 months, including 57 manual and 37 automated, 63 for chronic complications prevention, 30 for acute complications and one in the pre-operative setting. Mean decrease in sickle hemoglobin levels was higher in automated-red blood cell exchange (p exchange and access alarm on automated-red blood cell exchange. No major complication or alloimunization was recorded. Automated-red blood cell exchange decreased sickle hemoglobin levels more efficiently than manual procedure in the setting of acute and chronic complications of sickle cell disease, with minor technical concerns mainly due to vascular access. The threshold of sickle hemoglobin should be individualized for clinical and hematological goals. In our cohort of young patients, the need for an acceptable venous access was a limiting factor, but iron-overload was avoided. Automated red blood cell exchange is safe and well tolerated. It permits a higher sickle hemoglobin removal efficacy, better volume status control and iron-overload avoidance.

  10. [Blood transfusion assessment to 112 homozygous sickle-cell disease patients in university hospital of Brazzaville].

    Science.gov (United States)

    Dokekias, A Elira; Ossini, L Ngolet; Tsiba, F O Atipo; Malanda, F; Koko, I; De Montalembert, M

    2009-01-01

    Homozygous, sickle-cell disease (SCD) is responsible for acute complication, especially anaemic crisis and special situation such as acute chest syndrome, stroke and acute priapism. Pregnancy sickle-cell disease presents high risk for the mother and the fetus. In these indications, blood transfusion is the main therapy aiming to reduce anaemia in order to restore hemoglobin's rate or to increase normal Hb proportion. This study aims to assess the short-term efficiency of the red cell transfusion in SCD homozygous form. One hundred and twelve homozygous sickle-cell patients were enrolled in this prospective study: 59 females and 53 males, median age is 21,8 years (extremes: 2 and 45 years). These patients are mostly with very low income. Two groups of patients are included in this study. In the first group, patients present acute anemia crisis caused by infections disease (malaria, bacterial infections). In the second group (20 cases), SCD patients have particularly situations: pregnancy (10 cases); stroke (six cases); cardiac failure (two cases) and priapism (two cases). Transfusion treatment in first group is simple regimen. Transfusion of EC increased median Hb level at 2,9 g/dl (extremes: 1,1 and 4,7). In the second group of patients, 16 cases were transfused by manual partial exchange (1-3) and four patients received simple regimen of transfusion. Median Hb level was 3,1g/dl (extremes: 2,4-4,9 g/dl). HbS percentage reduction was after PTE between -30 and -66,8% (median: -52,6%). According to our diagnostic possibilities (blood serologic test), we have not found any contamination by HIV, HBV and HCV (virus).

  11. EXPRESSION OF A NEW A3 ANTIGEN IN THE CELLS OF PATIENTS WITH VARIOUS LYMPHOPROLIFERATIVE DISEASES

    Directory of Open Access Journals (Sweden)

    N. L. Deineko

    2014-01-01

    Full Text Available We have conducted a study of a novel monoclonal A3 antibody raised by means of hybridoma biotechnology. The study was performed with malignant cells of the patients with various lymphoproliferative disorders, and persons with nonmalignant diseases, as compared with intact lymphocytes from healthy people,using a method of immunocytochemical staining and indirect immunofluorescence technique. It was found that in cases of lymphoproliferative diseases with low proliferation rates, as based on the numbers of Ki-67 positive cells, as well as in non-malignant blood diseases, the A3 antigen was localized in nucleoli, and it was visualized as focal fluorescence. In malignant lymphoproliferative diseases with high proliferation indexes, the number of brightly fluorescent foci is observed, with formation of necklace-like structures within the nucleolar structures. The obtained data point to a diagnostic significance of A3 Mab in assessment of cellular proliferative rates in patients with various lymphoproliferative diseases. It was established that, in contrast to Ki-67, the proliferation stage could be determined for each cell, according to the number of fuorescent foci in nucleoli. This specific property of the A3 antigen points to its significance for diagnostics and malignancy staging of lymphoproliferative disorders.

  12. Metabolic rescue in pluripotent cells from patients with mtDNA disease.

    Science.gov (United States)

    Ma, Hong; Folmes, Clifford D L; Wu, Jun; Morey, Robert; Mora-Castilla, Sergio; Ocampo, Alejandro; Ma, Li; Poulton, Joanna; Wang, Xinjian; Ahmed, Riffat; Kang, Eunju; Lee, Yeonmi; Hayama, Tomonari; Li, Ying; Van Dyken, Crystal; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Koski, Amy; Mitalipov, Nargiz; Amato, Paula; Wolf, Don P; Huang, Taosheng; Terzic, Andre; Laurent, Louise C; Izpisua Belmonte, Juan Carlos; Mitalipov, Shoukhrat

    2015-08-13

    Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.

  13. Hematological differences between patients with different subtypes of sickle cell disease on hydroxyurea treatment

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    Fabia Neves

    2012-01-01

    Full Text Available OBJECTIVE: Sickle cell anemia and the interaction S/Beta thalassemia differ in hematological values due to microcytosis and hypochromia caused by the thalassemic mutation. The clinical benefit of long-term hydroxyurea treatment is undeniable in sickle cell disease with monitoring of the biological action of the drug being by the complete blood count. The objective of this work is to compare changes in some of the erythrocytic indexes between S/Beta thalassemia and sickle cell anemia patients on long-term hydroxyurea treatment. METHODS: The values of erythrocyte indexes (mean corpuscular volume and mean corpuscular hemoglobin were compared in a retrospective study of two groups of patients (Sickle cell anemia and S/Beta thalassemia on hydroxyurea treatment over a mean of six years. RESULTS: The quantitative values of the two parameters differed between the groups. Increases in mean corpuscular volume and reductions in mean corpuscular hemoglobin delay longer in S/Beta thalassemia patients (p-value = 0.018. CONCLUSION: Hematological changes are some of the beneficial effects of hydroxyurea in sickle cell disease as cellular hydration increases and the hemoglobin S concentration is reduced. The complete blood count is the best test to monitor changes, but the interpretation of the results in S/Beta thalassemia should be different.

  14. Modeling Red Blood Cell and Iron Dynamics in Patients with Chronic Kidney Disease

    Science.gov (United States)

    2012-02-10

    level in the body. Most patients with CKD have elevated levels of inflammation due to CKD and the presence of other medical issues (e.g., diabetes ...Blood, 37 (1971), 725–732. [11] Chung-Che Chang, Yayan Chen, Kapil Modi , Omar Awar, Clarence P. Alfrey, and Lawrence Rice, Changes of red blood cell...National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2008. [43] M. M. Udden, T. B. Driscoll, M

  15. Fecal bacteria from treatment-naive Crohn's disease patients can skew helper T cell responses.

    Science.gov (United States)

    Ma, Fei; Zhang, Yi; Xing, Junjie; Song, Xiaoling; Huang, Ling; Weng, Hao; Wu, Xiangsong; Walker, Emma; Wang, Zhongchuan

    2017-12-01

    Many studies have demonstrated that the inflamed mucosa of Crohn's disease (CD) patients presented a disturbed gut commensal community, and the shift in microbial composition and species variety is associated with disease severity. To establish a link between changes in the intestinal bacterial composition and the alteration of inflammation, we obtained fecal bacteria from CD patients and non-CD controls. The bacteria were then used to stimulate the peripheral blood mononuclear cells (PBMCs) from one non-CD individual. We found that the frequency of IFN-γ- and IL-17-expressing CD4 T cells was significantly higher after stimulation with CD bacteria than with non-CD bacteria, while the frequency of IL-4- and IL-10-expressing CD4 T cells was significantly decreased after stimulation with CD bacteria. A similar trend was observed in the level of cytokine expression and transcription expression. However, this difference was not clear-cut, as overlapping regions were observed between the two groups. With longer stimulation using CD bacteria, the skewing toward Th1/Th17 responses were further increased. This increase depended on the presence of monocytes/macrophages. Interestingly, we also found that B cells presented an inhibitory effect in CD bacteria-mediated skewing toward Th1/Th17 cells and promoted IL-10 secretion in CD bacteria-stimulated PBMCs. Together, our results demonstrated that CD bacteria could promote Th1/Th17 inflammation in a host factor-independent fashion. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Mutagenicity of hydroxyurea in lymphocytes from patients with sickle cell disease

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    Khayat André Salim

    2004-01-01

    Full Text Available Hydroxyurea is commonly used in the treatment of myeloproliferative diseases and in patients with sickle cell disease (SCD. The use of this antineoplastic agent in patients with SCD is justified because of the drug's ability to increase fetal hemoglobin levels, thereby decreasing the severity of SCD. However, high doses or prolonged treatment with hydroxyurea can be cytotoxic or genotoxic for these patients, with an increased risk of developing acute leukemia. This danger can be avoided by monitoring the lymphocytes of patients treated with hydroxyurea. Cytogenetic tests are important endpoints for monitoring the physiological effects of physical and chemical agents, including drugs. In this work, we assessed the genotoxicity of hydroxyurea in short-term cultures of lymphocytes from SCD patients. Hydroxyurea was not cytotoxic or genotoxic at the concentrations tested in the G2 phase of the cell cycle. These results support the use of hydroxyurea in the treatment of SCD, although further work is necessary to understand the effects of this drug in vivo.

  17. Cellular function reinstitution of offspring red blood cells cloned from the sickle cell disease patient blood post CRISPR genome editing

    Directory of Open Access Journals (Sweden)

    Jianguo Wen

    2017-06-01

    Full Text Available Abstract Background Sickle cell disease (SCD is a disorder of red blood cells (RBCs expressing abnormal hemoglobin-S (HbS due to genetic inheritance of homologous HbS gene. However, people with the sickle cell trait (SCT carry a single allele of HbS and do not usually suffer from SCD symptoms, thus providing a rationale to treat SCD. Methods To validate gene therapy potential, hematopoietic stem cells were isolated from the SCD patient blood and treated with CRISPR/Cas9 approach. To precisely dissect genome-editing effects, erythroid progenitor cells were cloned from single colonies of CRISPR-treated cells and then expanded for simultaneous gene, protein, and cellular function studies. Results Genotyping and sequencing analysis revealed that the genome-edited erythroid progenitor colonies were converted to SCT genotype from SCD genotype. HPLC protein assays confirmed reinstallation of normal hemoglobin at a similar level with HbS in the cloned genome-edited erythroid progenitor cells. For cell function evaluation, in vitro RBC differentiation of the cloned erythroid progenitor cells was induced. As expected, cell sickling assays indicated function reinstitution of the genome-edited offspring SCD RBCs, which became more resistant to sickling under hypoxia condition. Conclusions This study is an exploration of genome editing of SCD HSPCs.

  18. Combined analysis of circulating epithelial cells and serum thyroglobulin for distinguishing disease status of the patients with papillary thyroid carcinoma

    OpenAIRE

    Lin, Hung-Chih; Liou, Miaw-Jene; Hsu, Hsung-Ling; Hsieh, Jason Chia-Hsun; Chen, Yi-An; Tseng, Ching-Ping; Lin, Jen-Der

    2015-01-01

    Papillary thyroid carcinoma (PTC) accounts for about 80% of the cases in thyroid cancer. Routine surveillance by serum thyroglobulin (Tg) and medical imaging is the current practice to monitor disease progression of the patients. Whether enumeration of circulating epithelial cells (CECs) helps to define disease status of PTC patients was investigated. CECs were enriched from the peripheral blood of the healthy control subjects (G1, n = 17) and the patients at disease-free status (G2, n = 26) ...

  19. Autoantigens targeted in scleroderma patients with vascular disease are enriched in endothelial lineage cells

    Science.gov (United States)

    McMahan, Zsuzsanna H.; Cottrell, Tricia R.; Wigley, Fredrick M.; Antiochos, Brendan; Zambidis, Elias T.; Park, Tea Soon; Halushka, Marc K.; Gutierrez-Alamillo, Laura; Cimbro, Raffaello; Rosen, Antony; Casciola-Rosen, Livia

    2016-01-01

    Objective Scleroderma patients with autoantibodies to centromere proteins (CENPs) and/or interferon-inducible protein 16 (IFI16) are at increased risk of severe vascular complications. We set out to define whether these autoantigens are enriched in cells of the vasculature. Methods Successive stages of embryoid bodies (EBs) as well as vascular progenitors were used to evaluate the expression of scleroderma autoantigens IFI16 and CENP by immunoblotting. CD31 was included to mark early blood vessels. IFI16 and CD31 expression were defined in skin paraffin sections from scleroderma patients and from healthy controls. IFI16 expression was determined by flow cytometry in circulating endothelial cells (CECs) and circulating progenitor cells (CPCs). Results Expression of CENP-A, IFI16 and CD31 was enriched in EBs at days 10 and 12 of differentiation, and particularly in cultures enriched in vascular progenitors (IFI16, CD31, CENPs A and-B). This pattern was distinct from that of comparator autoantigens. Immunohistochemical staining of skin paraffin sections showed enrichment of IFI16 in CD31-positive vascular endothelial cells in biopsies from scleroderma patients and normal controls. Flow cytometry analysis revealed IFI16 expression in CPCs, but minimal expression in CECs. Conclusion Expression of scleroderma autoantigens IFI16 and CENPs, which are associated with severe vascular disease, is increased in vascular progenitors and mature endothelial cells. High level, lineage-enriched expression of autoantigens may explain the striking association between clinical phenotypes and the immune targeting of specific autoantigens. PMID:27159521

  20. Increased FKBP51 in induced sputum cells of chronic obstructive pulmonary disease patients after therapy

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    Holownia A

    2009-12-01

    Full Text Available Abstract Objective Immunophilin FKBP51 assists polypeptide folding, participates in glucocorticoid actions and may play a role in glucocorticoid resistance. FKBP51 is altered in patients with asthma, but its role in chronic obstructive pulmonary disease (COPD characterized by dysregulation of several pro/antiinflammatory genes is less clear. Methods We assessed changes in nuclear/cytosolic FKBP51 protein using SDS-PAGE/WB and FKBP51 mRNA by qRT-PCR in cells isolated from induced sputum of stable COPD patients treated with formoterol/budesonide or formoterol/budesonide/theophylline for 4 wk. Results Expression of FKBP51 was higher in formoterol/budesonide/theophylline-treated patients, compared with formoterol/budesonide group in both cytosolic and nuclear fractions by about 57% and 31%, respectively (P Conclusions Increased FKBP51 in COPD patients treated with formoterol/budesonide/theophylline may be important in altering signaling from corticosteroid receptors.

  1. Effect of L-arginine supplementation on immune responsiveness in patients with sickle cell disease.

    Science.gov (United States)

    Scavella, Arnette; Leiva, Lily; Monjure, Hanh; Zea, Arnold H; Gardner, Renee V

    2010-08-01

    L-arginine (L-Arg) is deficient in sickle cell disease (SSD) during vasoocclusion. We investigated possible causal relationship between L-Arg deficiency and immune dysfunction in SSD in steady-state. Fifteen patients with SSD in steady-state and 13 controls were studied. Plasma L-Arg levels were measured using liquid chromatography. T cell subsets and CD3zeta (CD3zeta) chain expression were analyzed using flow cytometry. Lymphocyte proliferative response to phytohemagglutinin (PHA) and production of IL-6 and interferon-gamma (IFN-gamma) were evaluated with and without L-Arg. SSD patients had significantly lower L-Arg levels than controls. CD3 and CD19 cell populations were comparable for both groups, but SSD patients had above normal numbers of natural killer cells (P = 0.06). Patients and controls exhibited significantly increased lymphocyte blastogenesis to PHA after introduction of L-Arg to cultures; response of patients was significantly greater than values for control individuals. Proliferative response to candida in SSD patients was significantly lower than in controls; L-Arg supplementation did not increase this response. L-Arg had no effect on blastogenic response to PPD and candida albicans. No effect was likewise seen in production of IL-6 and IFN-gamma after addition of L-Arg. CD3zeta chain expression increased after addition of L-Arg in both groups; differences were insignificant. L-Arg levels in steady-state SSD are significantly lower than in controls. L-Arg supplementation enhanced lymphocyte blastogenesis to PHA for both controls and patients, but not in response to antigen. There were no significant differences in CD3zeta chain expression although upregulation of expression occurred after L-Arg supplementation for both groups. (c) 2010 Wiley-Liss, Inc.

  2. Sonographic assessment of spleen size in Saudi patients with sickle cell disease

    International Nuclear Information System (INIS)

    Al-Salem, Ahmed H.; Al-Aithan, S.; Al-Jama, A.; Al-Dabbous, I.; Bhamidipati, P.

    1998-01-01

    In patients with SCD, the spleen commonly enlarges during the first two decades of life but then undergoes autosplenectomy due to repeated attacks of vaso-occlusion and infarction. This, however, is not the case in Saudi patients with SCD (340 SCD and 23-sickle beta-thalassemia). A total of 363 patients were evaluated. There ages ranged from 1-60 years (mean 60 years). Only 24 (6.6%) of our patients had autosplenectomy. The splenic index increased with age until about 40 years of age and then gradually decreased indicating persistence of splenomegaly in our patients into an older age group. Forty-three patients (11.8%) had marked-massive splenomegaly (splenic index >120cm) and these had higher HbF levels (mean HbF=22.2%) when compared with those who had autosplenectomy (mean HbF=14.6). This is significant (P-value=0.0169) and confirms the effect of HbF on persistence of splenomegaly in SCD patients. Ultrasonography is a simple, safe and accurate method of assessing splenic size in patients with sickle cell disease. Patients with persistent splenomegaly should be followed closely for development of complications which may necessitate splenectomy. (author)

  3. Lead Toxicity in the Pediatric Patient with Sickle Cell Disease: Unique Risks and Management.

    Science.gov (United States)

    Jung, Josephine Misun; Peddinti, Radhika

    2018-01-01

    Lead toxicity is the result of lead ingestion, one of the most common ingestions in the pediatric population. Nationwide and statewide efforts to recognize and curtail this epidemic have led to declining rates of toxicity. In patients with sickle cell disease (SCD), lead toxicity can be an elusive diagnosis due to overlapping symptom profiles, and inconsistent follow-up with a primary care physician can make the diagnosis even more difficult. In this article, two illustrative cases of lead toxicity in patients with SCD are described. The discussion reviews the current risk factors, screening, and inpatient management of lead toxicity, as well as describing the unique and sometimes confounding presentations of lead toxicity versus sickle cell crisis. [Pediatr Ann. 2018;47(1):e36-e40.]. Copyright 2018, SLACK Incorporated.

  4. Role of hydroxycarbamide in prevention of complications in patients with sickle cell disease

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    NM Wiles

    2009-09-01

    Full Text Available NM Wiles, J HowardDepartment of Haematology, St Thomas’ Hospital, Westminster, Bridge Road, London, SE1 7EH, UKAbstract: Sickle cell disease (SCD is a genetically inherited condition caused by a point mutation in the beta globin gene. This results in the production of the abnormal hemoglobin, sickle hemoglobin (HbS. Hydroxycarbamide, is an antimetabolite/cytotoxic which works by inhibiting ribonucleotide reductase, blocking the synthesis of DNA and arresting cells in the S phase. In sickle cell anemia, it promotes fetal hemoglobin (HbF synthesis, improves red cell hydration, decreases neutrophil and platelet count, modifies red cell endothelial cell interactions and acts as a nitric oxide donor. Trials have shown the clinical benefit of hydroxycarbamide in a subpopulation of adult patients with SCD, with a 44% reduction in the median annual rate of painful crises, a decrease in the incidence of acute chest syndrome and an estimated 40% reduction in overall mortality over a 9-year observational period. Its use in pediatrics has also been well established; trials have shown it is well tolerated and does not impair growth or development. In addition it decreases the number and duration of hospital attendences. A number of emerging uses of hydroxycarbamide currently are being investigated, such as stroke prevention.Keywords: sickle cell anemia, hydroxycarbamide, hydroxyurea, maximum tolerated dose, vaso-occlusive crisis

  5. Transcranial Doppler Ultrasound in Peninsular Arab Patients With Sickle Cell Disease.

    Science.gov (United States)

    Adekile, Adekunle; Hassan, Meaad; Asbeutah, Akram; Al-Hinai, Mohamed; Trad, Omar; Farhan, Nayef

    2018-05-06

    Transcranial Doppler ultrasound is used to identify patients with sickle cell disease (SCD) at risk for stroke. We performed transcranial Doppler studies in patients from 4 countries in the Arabian Peninsula (Kuwait, Oman, Iraq, and United Arab Emirates) to document the prevalence of abnormal transcranial Doppler findings. The patients were recruited from outpatient clinics and studied in a steady state. Transcranial Doppler examinations were performed with standard equipment by experienced operators. The time-averaged maximum mean velocity (TAMMV) was documented in the arteries of the circle of Willis. The hemoglobin (Hb) genotype was confirmed, and the fetal Hb level and complete blood counts were determined. There were 415 patients in the study, aged 2 to 18 years (mean ± SD, 8.6 ± 3.5 years). None of the patients had an abnormal TAMMV (ie, > 200 cm/s), whereas only 13 (3.1%), all from Iraq, had conditional values (170-200 cm/s) in the right middle cerebral artery and 7 (1.7%) in the left middle cerebral artery. There were no consistent TAMMV differences among male and female patients or in patients with different Hb genotypes (sickle cell anemia, sickle cell β 0- thalassemia, and sickle D). The use of hydroxyurea was associated with a lower TAMMV, whereas a blood transfusion history had no influence. Total hemoglobin, reticulocyte count, serum bilirubin, and fetal Hb values showed varying degrees of association with the TAMMV in the different vessels. This study has demonstrated the rarity of abnormal transcranial Doppler findings among Peninsular Arab patients with SCD. The guidelines for transcranial Doppler screening in this population need further studies and recommendations. © 2018 by the American Institute of Ultrasound in Medicine.

  6. Foetal haemoglobin and disease severity in sickle cell anaemia patients in Kampala, Uganda

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    Mpalampa Lena

    2012-09-01

    Full Text Available Abstract Background Sickle cell anaemia (SCA is a major chronic health problem in Uganda. In patients with SCA, the level of foetal haemoglobin (HbF has been found to be important in influencing the clinical course of the disease. Thus populations with high levels of HbF like those in Saudi Arabia have been described as having a milder clinical course with fewer complications as compared to populations with lower levels. Disease modifying drugs can increase the Hb F levels and modify the presentation of SCA. Methods This was a cross sectional study in which we determined foetal haemoglobin levels and examined the relationship between HbF levels and disease severity in SCA patients in Mulago Hospital, Kampala, Uganda. We consecutively enrolled 216 children aged 1 year to 18 years with SCA attending the Sickle Cell Clinic at Mulago Hospital whose guardians had given consent. The history included age at onset of initial symptoms and diagnosis, number of hospitalisations and blood transfusions and other complications of SCA (cardiovascular accidents, avascular hip necrosis and priapism. A detailed physical examination was performed to assess the current state and help describe the disease severity for each patient. Blood samples were drawn for HbF levels. HbF levels ≥10% was defined as high. Results Of the 216 children, (80 37% had HbF levels ≥10%. Significant correlations were observed between HbF level and several clinical parameters independent of age including age at diagnosis (p value 0.013, number of hospitalisations (p value 0.024 and transfusions (p value 0.018 since birth. Conclusion A third of the children with SCA attending the Sickle cell clinic in Mulago Hospital have high HbF levels. Higher HbF level is associated with later onset of symptoms and presentation, and less severe disease characterised by fewer hospitalisations and blood transfusions. We suggest HbF levels should be determined at initial contact for patients with SCA to

  7. Lesional accumulation of CD163-expressing cells in the gut of patients with inflammatory bowel disease.

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    Eleonora Franzè

    Full Text Available Monocytes/macrophages displaying different markers of activation/differentiation infiltrate the inflamed gut of patients with inflammatory bowel diseases (IBD, but the role that each monocyte/macrophage subpopulation plays in the pathogenesis of IBD is not fully understood. The hemoglobin scavenger receptor CD163, a specific marker of monocytes/macrophages, has been associated with either anti-inflammatory or inflammatory functions of macrophages in several pathologies. In this study we examined the tissue distribution and function of CD163-expressing monocytes/macrophages in IBD. CD163 RNA and protein expression was more pronounced in IBD in comparison to normal controls, with no significant difference between Crohn's disease and Ulcerative colitis. In IBD, over-expression of CD163 was restricted to areas with active inflammation and not influenced by current therapy. Immunohistochemical analysis confirmed the accumulation of CD163-expressing cells in IBD, mostly around and inside blood vessels, thus suggesting that these cells are partly recruited from the systemic circulation. Indeed, FACS analysis of circulating mononuclear cells showed that the fractions of CD163-positive monocytes were increased in IBD patients as compared to controls. Functionally, interleukin-6 up-regulated CD163 expression in lamina propria mononuclear cells and mucosal explants of normal subjects. In IBD blood and mucosal cell cultures, cross-linking of CD163 with a specific monoclonal anti-CD163 antibody enhanced tumor necrosis factor-α synthesis. These findings indicate that IBD mucosa is abundantly infiltrated with CD163-positive cells, which could contribute to amplify the inflammatory cytokine response.

  8. Dendritic cell chimerism in oral mucosa of transplanted patients affected by graft-versus-host disease.

    Science.gov (United States)

    Pérez, Claudio A; Rabanales, Ramón; Rojas-Alcayaga, Gonzalo; Larrondo, Milton; Escobar, Alejandro F; López, Mercedes N; Salazar-Onfray, Flavio; Alfaro, Jorge I; González, Fermín E

    2016-02-01

    Graft-versus-host disease (GVHD) is one of the main complications after haematopoietic stem cell transplantation. Clinical features of GVHD include either an acute (aGVHD) or a chronic (cGVHD) condition that affects locations such as the oral mucosa. While the involvement of the host's dendritic cells (DCs) has been demonstrated in aGVHD, the origin (donor/host) and mechanisms underlying oral cGVHD have not been completely elucidated. In this study, we intend to determine the origin of DCs present in mucosal tissue biopsies from the oral cavity of transplanted patients affected by cGVHD. We purified DCs, from oral biopsies of three patients with cGVHD, through immunobeads and subsequently performed DNA extraction. The origin of the obtained DCs was determined by PCR amplification of 13 informative short tandem repeat (STR) alleles. We also characterised the DCs phenotype and the inflammatory infiltrate from biopsies of two patients by immunohistochemistry. Clinical and histological features of the biopsies were concordant with oral cGVHD. We identified CD11c-, CD207- and CD1a-positive cells in the epithelium and beneath the basal layer. Purification of DCs from the mucosa of patients affected by post-transplantation cGVHD was >95%. PCR-STR data analysis of DCs DNA showed that 100% of analysed cells were of donor origin in all of the evaluated patients. Our results demonstrate that resident DCs isolated from the oral tissue of allotransplanted patients affected by cGVHD are originated from the donor. Further research will clarify the role of DCs in the development and/or severity of oral cGVHD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. N-acetylcysteine normalizes the urea cycle and DNA repair in cells from patients with Batten disease.

    Science.gov (United States)

    Kim, June-Bum; Lim, Nary; Kim, Sung-Jo; Heo, Tae-Hwe

    2012-12-01

    Batten disease is an inherited disorder characterized by early onset neurodegeneration due to the mutation of the CLN3 gene. The function of the CLN3 protein is not clear, but an association with oxidative stress has been proposed. Oxidative stress and DNA damage play critical roles in the pathogenesis of neurodegenerative diseases. Antioxidants are of interest because of their therapeutic potential for treating neurodegenerative diseases. We tested whether N-acetylcysteine (NAC), a well-known antioxidant, improves the pathology of cells from patients with Batten disease. At first, the expression levels of urea cycle components and DNA repair enzymes were compared between Batten disease cells and normal cells. We used both mRNA expression levels and Western blot analysis. We found that carbamoyl phosphate synthetase 1, an enzyme involved in the urea cycle, 8-oxoguanine DNA glycosylase 1 and DNA polymerase beta, enzymes involved in DNA repair, were expressed at higher levels in Batten disease cells than in normal cells. The treatment of Batten disease cells with NAC for 48 h attenuated activities of the urea cycle and of DNA repair, as indicated by the substantially decreased expression levels of carbamoyl phosphate synthetase 1, 8-oxoguanine DNA glycosylase 1 and DNA polymerase beta proteins compared with untreated Batten cells. NAC may serve in alleviating the burden of urea cycle and DNA repair processes in Batten disease cells. We propose that NAC may have beneficial effects in patients with Batten disease. Copyright © 2012 John Wiley & Sons, Ltd.

  10. Dyspnea, pulmonary function and exercise capacity in adult Saudi patients with sickle cell disease

    International Nuclear Information System (INIS)

    Alameri, Hatem F.; Alem, A.; Al-Momen, A.; Kardas, W.; Owais, M.; Jehangir, A.

    2008-01-01

    Objective was to examine pulmonary function, dyspnea, and exercise capacity in adult Saudi patients with sickle cell disease (SCD) patients. The patients were recruited from the hematology clinic at King Khalid University Hospital in Riyadh from January to December 2005. The study involved 39 patients with stable SCD 20 women and 19 men, with a mean age of 22.7+/- 7.1 years, hemoglobin level of 95.5+/-14.6g/L and hemoglobin F level of 13.7+/08.6. Patients underwent pulmonary function tests PFT forced expiratory volume in first second [FEV1], forced vital capacity [FVC], and diffusion capacity of carbon monoxide [DLco] data are presented as a percentage of the normal prediction, a 6- minute walk test 6MWT and echocardiography. Dyspnea was assessed using the Borg score. The 6MWT data were compared to body mass index matched healthy controls. Forty-one percent of SCD patients had mild dyspnea at rest and this increased to 61% at the end of the 6MWT. Pulmonary function tests were abnormal in 51%, 36% of patients had a restrictive pattern, 10% had isolated decrease in DLco and 5% had a mixed restrictive-obstrutive pattern. The 6MWD was shorter in SCD patients compared to the controls 368+/-67 versus 407+/-47m, p=0.005. No hematological variables correlated with outcome variables. Chronic pulmonary complications in adult Saudi SCD patients are relatively mild but common. Pulmonary function in these patients differs from that published for African-origin SCD patients. The difference may reflect a different natural history of SCD in the 2 populations. (author)

  11. A Patient-Centered Emergency Department Management Strategy for Sickle-Cell Disease Super-Utilizers.

    Science.gov (United States)

    Simpson, Grant G; Hahn, Hallie R; Powel, Alex A; Leverence, Robert R; Morris, Linda A; Thompson, Lara G; Zumberg, Marc S; Borde, Deepa J; Tyndall, Joseph A; Shuster, Jonathan J; Yealy, Donald M; Allen, Brandon R

    2017-04-01

    A subpopulation of sickle-cell disease patients, termed super-utilizers, presents frequently to emergency departments (EDs) for vaso-occlusive events and may consume disproportionate resources without broader health benefit. To address the healthcare needs of this vulnerable patient population, we piloted a multidisciplinary intervention seeking to create and use individualized patient care plans that alter utilization through coordinated care. Our goals were to assess feasibility primarily, and to assess resource use secondarily. We evaluated the effects of a single-site interventional study targeted at a population of adult sickle-cell disease super-utilizers using a pre- and post-implementation design. The pre-intervention period was 06/01/13 to 12/31/13 (seven months) and the post-intervention period was 01/01/14 to 02/28/15 (14 months). Our approach included patient-specific best practice advisories (BPA); an ED management protocol; and formation of a "medical home" for these patients. For 10 subjects targeted initially we developed and implemented coordinated care plans; after deployment, we observed a tendency toward reduction in ED and inpatient utilization across all measured indices. Between the annualized pre- and post-implementation periods we found the following: ED visits decreased by 16.5 visits/pt-yr (95% confidence interval [CI] [-1.32-34.2]); ED length of state (LOS) decreased by 115.3 hours/pt-yr (95% CI [-82.9-313.5]); in-patient admissions decreased by 4.20 admissions/pt-yr (95% CI [-1.73-10.1]); in-patient LOS decreased by 35.8 hours/pt-yr (95% CI [-74.9-146.7]); and visits where the patient left before treatment were reduced by an annualized total of 13.7 visits. We observed no patient mortality in our 10 subjects, and no patient required admission to the intensive care unit 72 hours following discharge. This effort suggests that a targeted approach is both feasible and potentially effective, laying a foundation for broader study.

  12. Acute Chest Syndrome in Sickle Cell Disease Patients Post Caesarean Delivery

    Directory of Open Access Journals (Sweden)

    YM Zhang

    2016-02-01

    Full Text Available Sickle cell disease (SCD is the most common inherited disease worldwide and is associated with anaemia and intermittent painful crisis. Pregnant women who are affected are known to have increased maternal and fetal mortality and morbidity. Acute chest syndrome (ACS is an uncommon but serious complication in pregnant women with SCD that can lead to death. We present two cases of patients with SCD, both of whom had severe ACS within 24 hours post Caesarean section. By accurate diagnosis and appropriate management by a multidisciplinary team, both mothers and fetuses had excellent outcomes. It is suggested that prompt recognition of ACS in a pregnant woman with SCD and collaborative medical and obstetric management are essential to optimize maternal and fetal outcomes.

  13. Frequency of red cell, leukocytic and platelet alloantibodies in patients with hematological diseases

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    N. V. Mineeva

    2014-07-01

    Full Text Available History of multiple transfusions in patients with hematological diseases increases the likelihood of immunization to donor blood cells antigensand immunological complications development. Incidence of alloantibodies development in this patients was assessed in this work. Alloantibodies detection was performed in patients with aplastic anemia, acute leukemia, chronic lymphocytic leukemia, and autoimmune thrombocytopenia. 9696 patients were included in this study. Frequency of alloantibodies to red cell antigens was 3.8 %, with 0.9 % of the antibody belong to the immunoglobulin G, and 2.9 % of the cases – to immunoglobulin M. Most of the IgG antibodies had following specificity:monospecific anti-D antibody (21 cases, anti-DC and anti-DE antibodies (4 cases, anti-C (8 cases, anti-E (15, anti-c (13, and anti-K (11. Anti-e (1, anti-Fya (2, anti-Lea (4, anti-S (2, anti-s (2, anti-Jka (2 antibodies were less common. Granulocytes antibodies were found in 66.7 % of 384 patients, with results dependent on the detection method used. The presence of antiplatelet alloantibodies studied in 285 serum samples, of which antibodies were detected in 99 patients (34.7 %. Specificity of platelet antibodies was determined in three serum samples only: anti-2b, anti-1a, anti-1b. In other patients, probably present antibodies to several antigens simultaneously, and to identify them was not possible.

  14. Peripheral-type benzodiazepine receptors in bronchoalveolar lavage cells of patients with interstitial lung disease

    International Nuclear Information System (INIS)

    Branley, Howard M.; Bois, Roland M. du; Wells, Athol U.; Jones, Hazel A.

    2007-01-01

    Introduction: PK11195 is a ligand with high affinity for peripheral benzodiazepine receptors (PBRs), which are present in large numbers in macrophages. PBRs play a role in antioxidant pathways and apoptosis, key factors in control of lung health. Intrapulmonary PBRs, assessed in vivo by positron emission tomography (PET), are decreased in interstitial lung disease (ILD) despite increased macrophage numbers. We wished to ascertain whether the observed decrease in in vivo expression of PBRs in the PET scans could be accounted for by a reduction in PBRs per cell by saturation-binding assays of R-PK11195 in cells obtained by bronchoalveolar lavage (BAL). Methods: We performed receptor saturation-binding assays with [ 3 H]-R-PK11195 on a mixed population of cells recovered by BAL to quantify the number of R-PK11195 binding sites per macrophage in 10 subjects with ILD and 10 normal subjects. Results: Receptor affinity [dissociation constant (Kd)] was similar in ILD patients and controls. However, R-PK11195 binding sites per cell [(maximal binding sites available (B max )] were decreased in macrophages obtained by BAL from subjects with ILD compared to normal (P<.0005). Microautoradiography confirmed localization of R-PK11195 to macrophages in a mixed inflammatory cell population obtained by BAL. Conclusion: These results demonstrate that in vitro PBR expression per cell on macrophages obtained by BAL is reduced in patients with ILD indicating a potentially functionally different macrophage phenotype. As PBRs are involved in the orchestration of lung inflammatory responses, this finding offers further insight into the role of macrophages in the pathogenesis of ILDs and offers a potential avenue for pharmacological strategy

  15. Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity.

    Science.gov (United States)

    Kwon, Yong-Soo; Cho, Young-Nan; Kim, Moon-Ju; Jin, Hye-Mi; Jung, Hyun-Ju; Kang, Jeong-Hwa; Park, Ki-Jeong; Kim, Tae-Jong; Kee, Hae Jin; Kim, Nacksung; Kee, Seung-Jung; Park, Yong-Wook

    2015-05-01

    Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. The aims of this study were to examine the levels of MAIT cells in pulmonary tuberculosis (TB) and nontuberculous mycobacteria (NTM) lung disease patients, to evaluate the clinical relevance of MAIT cell levels, and to investigate the functions of MAIT cells. Patients with pulmonary TB (n = 35), NTM (n = 29), and healthy controls (n = 75) were enrolled in the study. MAIT cell levels and functions were measured by flow cytometry. Circluating MAIT cell levels were found to be reduced in TB and NTM patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAIT cell numbers were significantly correlated with sputum AFB positivity, extent of disease, hemoglobin levels, lymphocyte counts, CRP and ESR levels. MAIT cells in TB patients failed to produce interferon-γ irrespective of the mode of stimulation, whereas NTM patients displayed a defect in MR1-dependent signaling pathway. Notably, an elevated expression of programmed death-1 was also associated with MAIT cell deficiency in TB. This study shows that MAIT cells are numerically and functionally deficient in TB and NTM patients and these deficiencies could contribute to immune system dysreguation in mycobacterial infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. High Dose Cyclophosphamide without Stem Cell Rescue in 207 Patients with Aplastic anemia and other Autoimmune Diseases

    Science.gov (United States)

    DeZern, Amy E.; Petri, Michelle; Drachman, Daniel B.; Kerr, Doug; Hammond, Edward R.; Kowalski, Jeanne; Tsai, Hua-Ling; Loeb, David M.; Anhalt, Grant; Wigley, Fredrick; Jones, Richard J.; Brodsky, Robert A.

    2011-01-01

    High-dose cyclophosphamide has long been used an anticancer agent, a conditioning regimen for hematopoietic stem cell transplantation and as potent immunosuppressive agent in autoimmune diseases including aplastic anemia. High-dose cyclophosphamide is highly toxic to lymphocytes but spares hematopoietic stem cells because of their abundant levels of aldehyde dehydrogenase, the major mechanism of cyclophosphamide inactivation. High dose cyclophosphamide therapy induces durable remissions in most patients with acquired aplastic anemia. Moreover, high-dose cyclophosphamide without hematopoietic stem cell rescue has shown activity in a variety of other severe autoimmune diseases. Here we review the history of cyclophosphamide as is applies to aplastic anemia (AA) and other autoimmune diseases. Included here are the historical data from early patients treated for AA as well as an observational retrospective study in a single tertiary care hospital. This latter component was designed to assess the safety and efficacy of high-dose cyclophosphamide therapy without stem cell rescue in patients with refractory autoimmune diseases. We analyzed fully the 140 patients with severe, progressive autoimmune diseases treated. All patients discussed here received cyclophosphamide, 50 mg/kg per day for 4 consecutive days. Response, relapse and overall survival were measured. Response was defined as a decrease in disease activity in conjunction with a decrease or elimination of immune modulating drugs. Relapse was defined as worsening disease activity and/or a requirement of an increase in dose of, or administration of new, immunosuppressive medications. Hematologic recovery occurred in all patients. The overall response rate of the was 95%, and 44% of those patients remain progression-free with a median follow up time of 36 (range 1–120) months for the 140 patients analyzed together. The overall actuarial and event free survival across all diseases at 60 months is 90.7% and 20

  17. Sickle Cell Disease

    Science.gov (United States)

    ... message, please visit this page: About CDC.gov . Learn Tips for Receiving Better Care in the Emergency Department in Our Fact ... related care in the United States. Read Supplement » VIDEO Sickle Cell Disease: When to Transfuse Learn about indications for blood transfusion in patients with ...

  18. Proteinuria in adult Saudi patients with sickle cell disease is not associated with identifiable risk factors

    Directory of Open Access Journals (Sweden)

    Aleem Aamer

    2010-01-01

    Full Text Available Renal involvement in patients with sickle cell disease (SCD is associated with signi-ficant morbidity and mortality. Proteinuria is common in patients with SCD and is a risk factor for future development of renal failure. We sought to identify risk factors, if any, associated with pro-teinuria in adult Saudi patients with SCD. We studied 67 patients with SCD followed-up at the King Khalid University Hospital, Riyadh, Saudi Arabia. All patients underwent 24-hour urine collection to measure creatinine clearance and to quantify proteinuria. In addition, blood was examined for evaluation of hematological and biochemical parameters. Clinical information was gathered from review of the patients′ charts. A urine protein level of more than 0.150 grams/24 hours was consi-dered abnormal. Urine protein was correlated with various clinical and laboratory parameters. Thirty-one males and 36 females were evaluated. The mean age of the cohort was 23.8 (± 7.2 years. Twenty-seven patients (40.3% had proteinuria of more than 0.150 grams/24 hours. The study group had a mean hemoglobin level of 8.5 (± 2.8 g/dL and mean fetal hemoglobin (HbF level of 14.4% (± 7.3%. Majority of the patients (61 had hemoglobin SS genotype and six patients had S-β0 thala-ssemia. None of the parameters evaluated correlated with proteinuria although there was a border-line association with older age and higher systolic blood pressure (P = 0.073 and 0.061 respec-tively. Hydroxyurea use for more than a year was not beneficial. In conclusion, our study suggests that proteinuria in adult Saudi patients is not associated with any clear identifiable risk factors.

  19. Regulatory B and T cell responses in patients with autoimmune thyroid disease and healthy controls

    DEFF Research Database (Denmark)

    Kristensen, Birte; Hegedüs, Laszlo

    2016-01-01

    ). HT is primarily a T-cell mediated disease, and whether B cells play a pathogenic role in the pathogenesis is still unclear. Both GD and HT are characterized by infiltration of the thyroid gland by self-reactive T cells and B cells. In the first paper of this thesis, the role of regulatory B cells...... (Bregs) and regulatory T cells (Tregs) were investigated in the context of GD and HT. First, we studied the role of the thyroid self-antigen, thyroglobulin (TG) in healthy donors. The self-antigen TG, but not the foreign recall antigen tetanus toxoid (TT), was able to induce interleukin 10 (IL-10......Autoimmune diseases occur due to faulty self-tolerance. Graves' disease (GD) and Hashimoto's thyroiditis (HT) are classic examples of organ-specific autoimmune diseases. GD is an auto-antibody-mediated disease where autoantibodies are produced against the thyroid stimulating hormone receptor (TSHR...

  20. Patient-specific induced pluripotent stem cells in neurological disease modeling: the importance of nonhuman primate models

    Directory of Open Access Journals (Sweden)

    Qiu Z

    2013-07-01

    Full Text Available Zhifang Qiu,1,2 Steven L Farnsworth,2 Anuja Mishra,1,2 Peter J Hornsby1,21Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA; 2Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USAAbstract: The development of the technology for derivation of induced pluripotent stem (iPS cells from human patients and animal models has opened up new pathways to the better understanding of many human diseases, and has created new opportunities for therapeutic approaches. Here, we consider one important neurological disease, Parkinson's, the development of relevant neural cell lines for studying this disease, and the animal models that are available for testing the survival and function of the cells, following transplantation into the central nervous system. Rapid progress has been made recently in the application of protocols for neuroectoderm differentiation and neural patterning of pluripotent stem cells. These developments have resulted in the ability to produce large numbers of dopaminergic neurons with midbrain characteristics for further study. These cells have been shown to be functional in both rodent and nonhuman primate (NHP models of Parkinson's disease. Patient-specific iPS cells and derived dopaminergic neurons have been developed, in particular from patients with genetic causes of Parkinson's disease. For complete modeling of the disease, it is proposed that the introduction of genetic changes into NHP iPS cells, followed by studying the phenotype of the genetic change in cells transplanted into the NHP as host animal, will yield new insights into disease processes not possible with rodent models alone.Keywords: Parkinson's disease, pluripotent cell differentiation, neural cell lines, dopaminergic neurons, cell transplantation, animal models

  1. Circulating gluten-specific FOXP3+CD39+ regulatory T cells have impaired suppressive function in patients with celiac disease.

    Science.gov (United States)

    Cook, Laura; Munier, C Mee Ling; Seddiki, Nabila; van Bockel, David; Ontiveros, Noé; Hardy, Melinda Y; Gillies, Jana K; Levings, Megan K; Reid, Hugh H; Petersen, Jan; Rossjohn, Jamie; Anderson, Robert P; Zaunders, John J; Tye-Din, Jason A; Kelleher, Anthony D

    2017-12-01

    Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3) + Treg cells. Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4 + T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4 + T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4 + T cells were FOXP3 + CD39 + Treg cells, which reside within the pool of memory CD4 + CD25 + CD127 low CD45RO + Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3 + CD39 + Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. This study provides the first estimation of FOXP3 + CD39 + Treg cell frequency within circulating gluten-specific CD4 + T cells after oral gluten challenge of patients with celiac disease. FOXP3 + CD39 + Treg cells comprised a major proportion of all circulating gluten-specific CD4 + T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key

  2. Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype

    Directory of Open Access Journals (Sweden)

    A. Hannemann

    2015-11-01

    Full Text Available Sickle cell disease (SCD in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals — but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.

  3. IMPACT OF MANNOSE-BINDING PROTEIN GENE POLYMORPHISMS IN OMANI SICKLE CELL DISEASE PATIENTS

    Directory of Open Access Journals (Sweden)

    Mathew Zachariah

    2016-02-01

    Full Text Available Objectives: Our objective was to study mannose binding protein (MBP polymorphisms in exonic and promoter region and correlate associated infections and vasoocculsive (VOC episodes, since MBP plays an important role in innate immunity by activating the complement system. Methods: We studied the genetic polymorphisms in the Exon 1 (alleles A/O and promoter region (alleles Y/X; H/L, P/Q of the MBL2 gene, in sickle cell disease (SCD patients as increased incidence of infections is seen in these patients. A PCR-based, targeted genomic DNA sequencing of MBL2 was used to study 68 SCD Omani patients and 44 controls (voluntary blood donors. Results: The observed frequencies of MBL2 promoter polymorphism (-221, Y/X were 44.4% and 20.5% for the heterozygous genotype Y/X and 3.2% and 2.2% for the homozygous (X/X respectively between SCD patients and controls. MBL2 Exon1 gene mutations were 29.4% and 50% for the heterozygous genotype A/O and 5.9% and 6.8% respectively for the homozygous (O/O genotype between SCD patients and controls. The distribution of variant MBL2 polymorphisms did not show any correlation in SCD patients with or without vasoocculsive crisis (VOC attacks (p=0.162; OR-0.486; CI=0.177 -1.33, however, it was correlated with infections (p=0.0162; OR-3.55; CI 1.25-10.04. Conclusions: Although the frequency of the genotypes and haplotypes of MBL2 in SCD patients did not differ from controls, overall in the SCD patient cohort the increased representation of variant alleles was significantly correlated with infections (p<0.05. However, these variant MBL2 polymorphisms did not seem to play a significant role in the VOC episodes in this SCD cohort. Keywords: Mannose-binding lectin, polymorphism, promoter, Sickle cell disease, MBL2, MBP

  4. Psychosocial stressors of sickle cell disease on adult patients in Cameroon.

    Science.gov (United States)

    Wonkam, Ambroise; Mba, Caryl Zameyo; Mbanya, Dora; Ngogang, Jeanne; Ramesar, Raj; Angwafo, Fru F

    2014-12-01

    Sickle Cell Disease (SCD) is a debilitating illness that affects quality of life. Studies of the psychosocial burden of SCD on patients have been rarely reported in Africa. We used a quantitative method, with face-to-face administered questionnaires, to study indices of psychosocial stressors on adult SCD patients in Cameroon. The questionnaire included a 36-item stress factors scale evaluating general perceptions of stress and five main stressors' domain: disease factors, hospital factors, financial factors, family factors and quality of personal-life factors. Items pertaining to psychosocial stressors involved four response options with increasing severity: 0, 1, 2 or 3. Non-parametric tests were used for analysis. The majority of the 83 participants were urban dwellers, female, 20-30 years old, single, unemployed, with at least a secondary or tertiary education. Median age at diagnosis was 100 months; 47.8% had >3 painful vaso-oclusive crises annually. Only 4.8% had been treated with hydroxyurea. The majority reported moderate to severe difficulty coping with SCD. The "degree of clinical severity" category displayed the highest median score (2.0), while familial stressors showed the lowest (0.8). Being female, married, with low education level, an additional affected sibling and low direct income were significantly associated with specific stressors' categories. In Cameroon, there is an urgent need to implement policies that ensure affordable access to health-care and practices to reduce SCD morbidity and improve patients' quality of life.

  5. Effector T-cells are expanded in systemic lupus erythematosus patients with high disease activity and damage indexes.

    Science.gov (United States)

    Piantoni, S; Regola, F; Zanola, A; Andreoli, L; Dall'Ara, F; Tincani, A; Airo', P

    2018-01-01

    Background and objectives T-cell activation may be one of the pathogenic mechanisms of systemic lupus erythematosus (SLE). After repeated antigenic stimulation, T-cells undergo different modifications, leading to the differentiation into effector memory T-cells (CCR7-CD45RA-) and terminally differentiated effector memory (TDEM) T-cells (CCR7-CD45RA+). Similarly, down-modulation of CD28 may lead to the expansion of the CD28- T-cells, a subpopulation with peculiar effector activities. The aim of this study was the characterization of T-cell phenotype in a cohort of patients with SLE according to disease activity and damage index. Materials and methods Phenotypic analysis of peripheral blood T lymphocytes of 51 SLE patients and 21 healthy controls was done by flow-cytometry. SLE disease activity was evaluated by SLE Disease Activity Index-2000 (SLEDAI-2K) and damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). The variations between different groups were evaluated by Mann-Whitney test. Bonferroni correction was applied to adjust for multiple comparisons ( p adj ). Spearman rank test was used to evaluate the correlations between quantitative variables. Results CD4+ lymphopenia was found among SLE patients. Patients showed a trend for a higher percentage of TDEM among the CD4+ T-cell subpopulation in comparison with healthy controls ( p = .04). SLE patients were divided into two groups according to disease activity: patients with SLEDAI-2K ≥ 6 ( n = 13) had a higher percentage of circulating CD4+ T-cells with CD28- phenotype ( p adj  = .005) as well as those with an effector memory ( p adj  = .004) and TDEM ( p adj  = .002) phenotype and a trend of decrease of regulatory T-cells (TREGs) ( p = .02), in comparison with patients with low disease activity ( n = 38). Patients with damage (SDI ≥ 1) tended to show an expansion of TDEM among CD4+ T-cells as compared with

  6. Osteoporosis and Vitamin D Deficiency in Patients with Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Zeynep Ozdemir

    2016-07-01

    Full Text Available Aim: Bone disorders such as osteopenia or osteoporosis are the most common clinical manifestations seen in sickle cell disease (SCD with a high of morbidity. There are many reasons, including vitamin D deficiency for the appearance of bone problems. In the present study we aimed to evaluate osteopathy in patients with SCD using bone mineral densitometry (BMD and biochemical indices. Material and Method: 61 patients (29 female, 32 male were included in the study. The age, gender, and biochemical parameters with BMD were evaluated using dual energy X-ray absorptiometry from lumbar vertebrae. According to Z scores, [-2] was considered as osteoporosis. Multivariate analysis was performed to determine the factors influencing BMD. Results: There were a total of 61 SCD patients. The average age was 21.06±5.06 (15-27 years and the mean BMI was 19.15±2.98 kg/m2. 23 patients were osteopenic (11 female, 12 male (37.7% and 26 were osteoporotic (12 female, 13 male (44.3%. Twelve patients (6 female and 6 male (18% had normal Z scores. Vitamin D was found severely deficient (

  7. Allogeneic Hematopoietic Cell Transplantation for Older Patients: Prognosis Determined by Disease Risk Index.

    Science.gov (United States)

    He, Fiona; Cao, Qing; Lazaryan, Aleksandr; Brunstein, Claudio; Holtan, Shernan; Warlick, Erica; Ustun, Celalettin; McClune, Brian; Arora, Mukta; Rashidi, Armin; Eckfeldt, Craig; Weisdorf, Daniel J; Bejanyan, Nelli

    2017-09-01

    The treatment of elderly patients with advanced hematological malignancies has expanded to include reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT) as a potentially curative option. We studied the association between Disease Risk Index (DRI) and clinical outcomes of 196 elderly patients (median age, 64.8; range, 60 to 75 years) with hematological malignancies receiving RIC alloHCT (2000 to 2014). Donors were related and unrelated adults (n = 100, 51.1%) or umbilical cord blood (n = 96, 48.9%). DRI classified 12 patients (6.1%) as low risk (LR), 146 patients (74.5%) as intermediate risk (IR), and 38 patients (19.4%) as high risk (HR). Two-year overall survival (OS) was 47% (52% for LR/IR versus 29% for HR, P risk of relapse (hazard ratio, 2.07; 95% confidence interval [CI], 1.34 to 3.33; P = .02) and treatment failure (hazard ratio, 2.07; 95% CI, 1.35 to 3.18; P risk of relapse leading to poor survival in HR DRI, participation in clinical trials offering relapse prevention strategies after RIC alloHCT should be encouraged when available. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Relevance of blood groups in transfusion of sickle cell disease patients.

    Science.gov (United States)

    Noizat-Pirenne, France

    2013-03-01

    Blood groups are clinically significant in sickle cell disease (SCD) as transfusion remains a key treatment in this pathology. The occurrence of a delayed haemolytic transfusion reaction (DHTR) is not rare and is a life-threatening event. The main cause of DHTR is the production of alloantibodies against red blood cell antigens. The high rate of alloimmunization in SCD patients is mainly due to the differences of red blood groups between patients of African descent, and the frequently Caucasian donors. From an immuno-haematological point of view, DHTR in SCD patients has specific features: classical antibodies known to be haemolytic can be encountered, but otherwise non significant antibodies, autoantibodies and antibodies related to partial and rare blood groups are also frequently found in individuals of African descent. In some cases, there are no detectable antibodies. As alloimmunization remains the main cause of DHTR, it is extremely important to promote blood donation by individuals of African ancestry to make appropriate blood available. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  9. 78 FR 66747 - Sickle Cell Disease Public Meeting on Patient-Focused Drug Development

    Science.gov (United States)

    2013-11-06

    ... effects have the greatest impact on your life? (Examples may include pain crises, breathing problems... negative effects of your sickle cell disease? Please describe these treatments, which may include blood... you do to prevent or treat any negative effects of your sickle cell disease? Please describe any...

  10. Hydroxyurea Therapy Mobilises Arachidonic Acid from Inner Cell Membrane Aminophospholipids in Patients with Homozygous Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    A. A. Daak

    2011-01-01

    Full Text Available The cytotoxic compound hydroxyurea (HU is effective therapy for sickle cell disease. However, its effect on unsaturated membrane lipids is unknown. Red cell fatty acids were investigated in HU-treated (n=19 and HU-untreated (n=17 sickle cell patients and controls (n=20. The HU-treated compared with the HU-untreated patients had lower arachidonic (AA acid level in ethanolamine, physphoglycerids (EPG (22.9±1.2   versus   24.0±1.1%,  P<0.05 serine SPG (22.13±2.2   versus   24.9±2.3%,  P<0.01 phosphoglycerides. The treated patients and controls had comparable levels of docosahexaenoic (DHA and total n-3 fatty acids in EPG and choline phosphoglycerides (CPG. In contrast, the untreated group had significantly (P<0.05 lower DHA and total n-3 compared with the controls in EPG (2.7±0.4   versus   3.2±0.6% and 4.6±0.5   versus   5.2±0.7% and CPG (0.7±0.2   versus   1.0±0.2% and 1.2±0.2   versus   1.4±0.3. HU is known to activate cytosolic phospholipase A2 and cyclooxygenase 2, and from this study, it appears to induce mobilisation of AA from the inner cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may play a role in clinical improvements which occur in HU-treated patients.

  11. Implementation of Indigenous Electronic Medical Record System to Facilitate Care of Sickle Cell Disease Patients in Chhattisgarh.

    Science.gov (United States)

    Choubey, Mona; Mishra, Hrishikesh; Soni, Khushboo; Patra, Pradeep Kumar

    2016-02-01

    Sickle cell disease (SCD) is prevalent in central India including Chhattisgarh. Screening for SCD is being carried out by Government of Chhattisgarh. Electronic Medical Record (EMR) system was developed and implemented in two phases. Aim was to use informatics techniques and indigenously develop EMR system to improve the care of SCD patients in Chhattisgarh. EMR systems had to be developed to store and manage: i) huge data generated through state wide screening for SCD; ii) clinical data for SCD patients attending the outpatient department (OPD) of institute. 'State Wide Screening Data Interface' (SWSDI) was designed and implemented for storing and managing data generated through screening program. Further, 'Sickle Cell Patients Temporal Data Management System' (SCPTDMS) was developed and implemented for storing, managing and analysing sickle cell disease patients' data at OPD. Both systems were developed using VB.Net and MS SQL Server 2012. Till April 2015, SWSDI has data of 1294558 persons, out of which 121819 and 4087 persons are carriers and patients of sickle cell disease respectively. Similarly till June 2015, SCPTDMS has data of 3760 persons, of which 923 are sickle cell disease patients (SS) and 1355 are sickle cell carriers (AS). Both systems are proving to be useful in efficient storage, management and analysis of data for clinical and research purposes. The systems are an example of beneficial usage of medical informatics solutions for managing large data at community level.

  12. Regulatory B and T cell responses in patients with autoimmune thyroid disease and healthy controls

    DEFF Research Database (Denmark)

    Kristensen, Birte

    2016-01-01

    Autoimmune diseases occur due to faulty self-tolerance. Graves' disease (GD) and Hashimoto's thyroiditis (HT) are classic examples of organ-specific autoimmune diseases. GD is an auto-antibody-mediated disease where autoantibodies are produced against the thyroid stimulating hormone receptor (TSHR...... (Bregs) and regulatory T cells (Tregs) were investigated in the context of GD and HT. First, we studied the role of the thyroid self-antigen, thyroglobulin (TG) in healthy donors. The self-antigen TG, but not the foreign recall antigen tetanus toxoid (TT), was able to induce interleukin 10 (IL-10......) secretion by B cells and CD4+ T cells. These IL-10 producing B cells (B10 cells) from healthy donors were enriched with the CD5+ and CD24hi phenotype. In addition, TG was able to induce IL-6 production by B cells. In contrast, TT induced production of Th1-type pro-inflammatory cytokines including interferon...

  13. Responsibilities of Health Care Professionals in Counseling and Educating Patients With Incurable Neurological Diseases Regarding "Stem Cell Tourism": Caveat Emptor.

    Science.gov (United States)

    Bowman, Michelle; Racke, Michael; Kissel, John; Imitola, Jaime

    2015-11-01

    "Stem cell tourism" is a rising Internet-based industry that aims to offer unproven procedures to patients with incurable diseases. This unregulated activity is reaching the neurologist's office as well as across the world, as patients request information or clearance for such procedures. Herein, we posit the need for medical societies and licensing boards to bring this issue to the forefront of neurology because it has the potential to affect patient care with risk of morbidity and mortality, as well as to undermine public confidence in legitimate stem cell research for incurable neurological diseases such as multiple sclerosis and amyotrophic lateral sclerosis.

  14. Hydroxyurea in Pediatric Patients With Sickle Cell Disease: What Nurses Need to Know.

    Science.gov (United States)

    Rees, Allison L

    2016-09-01

    Sickle cell disease (SCD) is an inherited disorder in which sickled red blood cells occlude the small vessels of the body, reducing oxygen delivery to tissues and ultimately negatively affecting many of the body's major organs. Hydroxyurea has proven beneficial in the treatment of SCD and prevention of disease-related complications. The 2014 guidelines put forth by the National Heart, Lung, and Blood Institute recommend hydroxyurea treatment in infants 9 months and older, children, and adolescents with SCD-SS or SCD-Sβ(0) thalassemia regardless of clinical severity. This is a change from the 2002 guidelines in which hydroxyurea was recommended for adolescents and children with SCD-SS or SCD-Sβ(0) thalassemia with frequent episodes of pain, a history of acute chest syndrome, severe and symptomatic anemia or other severe vaso-occlusive events. Nurses play a critical role in working with patients and families to provide education, guidance, and support to improve compliance to mitigate the long-term effects of SCD. © 2015 by Association of Pediatric Hematology/Oncology Nurses.

  15. Phenotypic Diversity of Sickle Cell Disease in Patients with a Double Heterozygosity for Hb S and Hb D-Punjab.

    Science.gov (United States)

    Torres, Lidiane S; Okumura, Jéssika V; Belini-Júnior, Édis; Oliveira, Renan G; Nascimento, Patrícia P; Silva, Danilo G H; Lobo, Clarisse L C; Oliani, Sonia M; Bonini-Domingos, Claudia R

    2016-09-01

    Phenotypic heterogeneity for sickle cell disease is associated to several genetic factors such as genotype for sickle cell disease, β-globin gene cluster haplotypes and Hb F levels. The coinheritance of Hb S (HBB: c.20A > T) and Hb D-Punjab (HBB: c.364G > C) results in a double heterozygosity, which constitutes one of the genotypic causes of sickle cell disease. This study aimed to assess the phenotypic diversity of sickle cell disease presented by carriers of the Hb S/Hb D-Punjab genotype and the Bantu [- + - - - -] haplotype. We evaluated medical records from 12 patients with sickle cell disease whose Hb S/Hb D-Punjab genotype and Bantu haplotype were confirmed by molecular analysis. Hb S and Hb D-Punjab levels were quantified by chromatographic analysis. Mean concentrations of Hb S and Hb D-Punjab were 44.8 ± 2.3% and 43.3 ± 1.8%, respectively. Painful crises were present in eight (66.7%) patients evaluated, representing the most common clinical event. Acute chest syndrome (ACS) was the second most prevalent manifestation, occurring in two individuals (16.7%). Three patients were asymptomatic, while another two exhibited greater diversity of severe clinical manifestations. Medical records here analyzed reported a significant clinical diversity in sickle cell disease ranging from the absence of symptoms to wide phenotypic variety. The sickle cell disease genotype, Bantu haplotype and hemoglobin (Hb) levels did not influence the clinical diversity. Thus, we concluded that the phenotypic variation in sickle cell disease was present within a specific genotype for disease regardless of the β-globin gene cluster haplotypes.

  16. MRA of the intracranial circulation in asymptomatic patients with sickle cell disease

    International Nuclear Information System (INIS)

    Gillams, A.R.; McMahon, L.; Weinberg, G.; Carter, A.P.

    1998-01-01

    Background. MR angiography (MRA) provides a mechanism for non-invasively studying blood flow, thus providing a new opportunity to study the intracranial circulation in asymptomatic sickle cell disease (SCD) patients. Although conventional angiography is the gold standard for the depiction of vascular anatomy, this is too invasive for an asymptomatic population. Objective. To establish the range of appearances in asymptomatic SCD patients and to correlate brain MRI results (either sub-clinical abnormalities or normal brain parenchyma) with the MRA findings. Materials and methods. Brain MRI and MRA of the intracranial circulation was performed on 22 patients (13 male and 9 female, median age 7.5 years, range 1.3-20 years). Fourteen were homozygous SS and eight were SC. The median haematocrit at the time of MRI was 25.9 (range 13.8-33.3). Results. On MR imaging, four patients had infarcts in eight vascular territories (six anterior and two posterior). In 3/4 of anterior vascular territories with infarction, long (≥ 6 mm) segments of abnormal signal were seen at the internal carotid artery bifurcation with associated reduced distal flow. Short focal areas of abnormal signal were commonly seen where vessels branched, bifurcated or curved and were not associated with infarcts. These areas probably represent turbulence-related dephasing secondary to high velocity flow found in SCD. Conclusion. Long segments (≥ 6 mm) of abnormal signal with reduced distal flow correlated with sub-clinical infarction. (orig.)

  17. Disease-in-a-dish: the contribution of patient-specific induced pluripotent stem cell technology to regenerative rehabilitation.

    Science.gov (United States)

    Mack, David L; Guan, Xuan; Wagoner, Ashley; Walker, Stephen J; Childers, Martin K

    2014-11-01

    Advances in regenerative medicine technologies will lead to dramatic changes in how patients in rehabilitation medicine clinics are treated in the upcoming decades. The multidisciplinary field of regenerative medicine is developing new tools for disease modeling and drug discovery based on induced pluripotent stem cells. This approach capitalizes on the idea of personalized medicine by using the patient's own cells to discover new drugs, increasing the likelihood of a favorable outcome. The search for compounds that can correct disease defects in the culture dish is a conceptual departure from how drug screens were done in the past. This system proposes a closed loop from sample collection from the diseased patient, to in vitro disease model, to drug discovery and Food and Drug Administration approval, to delivering that drug back to the same patient. Here, recent progress in patient-specific induced pluripotent stem cell derivation, directed differentiation toward diseased cell types, and how those cells can be used for high-throughput drug screens are reviewed. Given that restoration of normal function is a driving force in rehabilitation medicine, the authors believe that this drug discovery platform focusing on phenotypic rescue will become a key contributor to therapeutic compounds in regenerative rehabilitation.

  18. Peripheral blood and intrathyroidal T cell clones from patients with thyroid autoimmune diseases.

    Science.gov (United States)

    Massart, C; Caroff, G; Maugendre, D; Genetet, N; Gibassier, J

    1999-01-01

    For a better understanding of the pathogenesis of thyroid autoimmune diseases, we have studied morphological and functional properties of T clones from peripheral blood lymphocytes (PBL) and from intrathyroidal lymphocytes (ITL) obtained from 3 patients with Graves' disease or 1 Hashimoto's thyroiditis. Investigations were carried out on clones cultured alone or cocultured with autologous thyrocytes. Clonage efficiency ranged from 30% to 33% for PBL and 10% to 36% for ITL. A predominance of CD4-positive clones was observed whatever the origin of the lymphocytes or the autoimmune pathology. Gamma interferon (IFN-gamma) was detected in the majority (17/19) of the clones tested. Intracytoplasmic interleukin (IL-4) was secreted in 7/19 clones and both cytokines were produced in 5/19 clones. In coculture a proliferative response and tumour necrosis factor (TNF-alpha) production were observed with 6 clones (4 from Graves thyrocytes and 2 from thyroiditis). No cytotoxic clone was derived from Graves or thyroiditis tissues. These data demonstrate that the large majority of T clones are principally CD4-T cells; all the clones secreted TNF-alpha and a large majority produced IFN-gamma. Only a few clones produced IL-4 alone or associated with IFN-gamma. Six T clones induced proliferative response and of TNF-alpha secretion in coculture. Further investigations must be performed on these antigen-reactive T clones to analyse their role in the pathogenesis of the human thyroid autoimmune diseases.

  19. The Effectiveness of Self-Management Programs on Self-Efficacy in Patients With Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Ahmadi

    2014-07-01

    Full Text Available Background Patients with sickle cell disease suffer from various complications during their lifetime. In order to cope with the disease, they must adapt themselves to a complex set of behaviors that promote self-management and prevent complications associated with the disease. Chronic disease self-management programs are a combination of strategies that increase self-efficacy and promote self-management behaviors. Objectives This study aimed to determine the effectiveness of self-management programs on self-efficacy in patients with sickle cell disease. Patients and Methods In this quasi-experimental study, 69 patients with sickle cell disease who were referred to the Thalassemia Clinic of Ahvaz Shafa Hospital were entered into the study through the census method. Then, the self-management program was implemented using the 5A method for 12 weeks. The Levels of pre and post intervention self-efficacy were assessed using the sickle cell self-efficacy scale (SCSES, while descriptive statistics, paired t-test and Wilcoxon test were used to analyze the data. Results Before the intervention, the majority of subjects (50.7% had moderate self-efficacy, whereas after the intervention, the majority of patients (81.2% showed high self-efficacy. The overall scores and scores of the post-intervention self-efficacy sub-groups were significantly increased (P < 0.001. Conclusions The results of this study showed that self-management interventions are effective in promoting self-efficacy in patients with sickle cell disease. Thus, the use of self-management programs is advisable to change behaviors and promote self-efficacy in such patients.

  20. T cell responses in senior patients with community-acquired pneumonia related to disease severity.

    Science.gov (United States)

    Bian, Lu-Qin; Bi, Ying; Zhou, Shao-Wei; Chen, Zi-Dan; Wen, Jun; Shi, Jin; Mao, Ling; Wang, Ling

    2017-12-01

    Senior individuals older than 65 years of age are at a disproportionally higher risk of developing pneumonia. Impaired capacity to defend against airway infections may be one of the reasons. It is generally believed that weaker regulatory T cell responses may be beneficial to host defense against pathogens. In senior patients with community-acquired bacterial pneumonia, we investigated the frequencies and functions of regulatory T cells. Interestingly, we found that compared to age- and sex-matched healthy controls, senior pneumonia patients presented lower frequencies of Foxp3-expressing and Helios-expressing CD4 + T cells. The quantity of Foxp3 and Helios being expressed, measured by their mRNA transcription levels, was also lower in CD4 + T cells from pneumonia patients. Furthermore, following TCR and TGF-β stimulation, pneumonia patients presented impaired capacity to upregulate Foxp3 and Helios. Functional analyses revealed that CD4 + T cells from pneumonia patients secreted lower amounts of IL-10 and TGF-β, two cytokines critical to regulatory T cell-mediated suppression. Also, the expression of granzyme B and perforin, which were cytolytic molecules potentially utilized by regulatory T cells to mediate the elimination of antigen-presenting cells and effector T cells, were reduced in CD4 + CD25 + T cells from senior pneumonia patients. In addition, the CD4 + CD25 + T cells from senior pneumonia patients presented reduced capacity to suppress effector CD4 + and CD8 + T cell proliferation. Moreover, the value of pneumonia severity index was inversely correlated with several parameters of regulatory T cell function. Together, our results demonstrated that senior pneumonia patients presented a counterintuitive impairment in regulatory T cell responses that was associated with worse prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Successful orthotopic liver transplantation in an adult patient with sickle cell disease and review of the literature

    Directory of Open Access Journals (Sweden)

    Morey Blinder

    2013-05-01

    Full Text Available Sickle cell disease can lead to hepatic complications ranging from acute hepatic crises to chronic liver disease including intrahepatic cholestasis, and iron overload. Although uncommon, intrahepatic cholestasis may be severe and medical treatment of this complication is often ineffective. We report a case of a 37 year-old male patient with sickle cell anemia, who developed liver failure and underwent successful orthotopic liver transplantation. Both pre and post-operatively, he was maintained on red cell transfusions. He remains stable with improved liver function 42 months post transplant. The role for orthotopic liver transplantation is not well defined in patients with sickle cell disease, and the experience remains limited. Although considerable challenges of post-transplant graft complications remain, orthotopic liver transplantation should be considered as a treatment option for sickle cell disease patients with end-stage liver disease who have progressed despite conventional medical therapy. An extended period of red cell transfusion support may lessen the post-operative complications.

  2. High frequency of cytolytic 21-Hydroxylase specific CD8+ T cells in autoimmune Addison’s disease patients1

    Science.gov (United States)

    Dawoodji, Amina; Chen, Ji-Li; Shepherd, Dawn; Dalin, Frida; Tarlton, Andrea; Alimohammadi, Mohammad; Penna-Martinez, Marissa; Meyer, Gesine; Mitchell, Anna L; Gan, Earn H; Bratland, Eirik; Bensing, Sophie; Husebye, Eystein; Pearce, Simon H.; Badenhoop, Klaus; Kämpe, Olle; Cerundolo, Vincenzo

    2016-01-01

    The mechanisms behind the destruction of the adrenal glands in autoimmune Addison’s disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in over 90% of patients, but these autoantibodies are not thought to mediate the disease. Here we demonstrate highly frequent 21-hydroxylase specific T cells detectable in 20 patients with Addison’s disease. Using overlapping 18aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8+ and CD4+ T cell responses in a large proportion of Addison’s patients both ex-vivo and after in-vitro culture of peripheral blood lymphocytes up to 20 years after diagnosis. In a large proportion of patients, CD8+ 21-hydroxylase specific T cells and CD4+ 21-hydroxylase specific T cells were very abundant and detectable in ex-vivo assays. HLA class-I tetramer-guided isolation of 21-hydroxylase specific CD8+ T cells showed their ability to lyse 21-hydroxylase positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate strong cytotoxic T lymphocyte responses to 21-hydroxylase often occur in-vivo, and that reactive cytotoxic T lymphocytes have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer. PMID:25063864

  3. Clinical Interpretation of Quantitative Sensory Testing as a Measure of Pain Sensitivity in Patients with Sickle Cell Disease

    OpenAIRE

    Brandow, Amanda M.; Panepinto, Julie A.

    2016-01-01

    Patients with sickle cell disease (SCD) display significantly lower mean/median thermal and mechanical pain thresholds compared to controls. This suggests impaired pain sensitivity where stimuli produce exaggerated pain. Despite these mean/median differences, clinicians need to understand if patients meet criteria for impaired pain sensitivity. We defined thresholds for impaired cold, heat, and mechanical pain sensitivity in SCD patients. Using quantitative sensory testing (QST) we assessed c...

  4. Tuberculous spondylodiscitis in a patient with a sickle-cell disease: CT findings

    International Nuclear Information System (INIS)

    Krupniewski, Leszek; Palczewski, Piotr; Gołębiowski, Marek; Kosińska-Kaczyńska, Katarzyna

    2012-01-01

    Although sickle-cell anemia (SCA) is common in black Americans, Sub-Saharan Africa and in the Mediterranean area, the disease is rare in the temperate climate zone. The manifestations of the disease are related mainly to the production of abnormal hemoglobin that leads to organ ischemia and increased susceptibility to infection caused by functional asplenia. The authors present CT findings in a 39-year-old black woman diagnosed due to abdominal pain, lymphadenopathy and fever. CT of the thorax and abdomen demonstrated changes in the liver, spleen, and skeletal system suggestive of SCA complicated with spondylodiscitis in the thoracic spine. Hepatomegaly and small calcified spleen are typical findings in older homozygotic patients with SCA. The lesions in the skeleton may be related either to intramedullary hematopoiesis or osteonecrosis and osteomyelitis. In the latter case, diffuse osteosclerosis and H-shaped vertebrae are most typical. Tuberculous spondylodiscitis is characterized by the location in the thoracic region, preferential involvement of anterior elements, relative sparing of intervertebral discs, and cold abscesses

  5. Tuberculous spondylodiscitis in a patient with a sickle-cell disease: CT findings.

    Science.gov (United States)

    Krupniewski, Leszek; Palczewski, Piotr; Gołębiowski, Marek; Kosińska-Kaczyńska, Katarzyna

    2012-01-01

    Although sickle-cell anemia (SCA) is common in black Americans, Sub-Saharan Africa and in the Mediterranean area, the disease is rare in the temperate climate zone. The manifestations of the disease are related mainly to the production of abnormal hemoglobin that leads to organ ischemia and increased susceptibility to infection caused by functional asplenia. The authors present CT findings in a 39-year-old black woman diagnosed due to abdominal pain, lymphadenopathy and fever. CT of the thorax and abdomen demonstrated changes in the liver, spleen, and skeletal system suggestive of SCA complicated with spondylodiscitis in the thoracic spine. Hepatomegaly and small calcified spleen are typical findings in older homozygotic patients with SCA. The lesions in the skeleton may be related either to intramedullary hematopoiesis or osteonecrosis and osteomyelitis. In the latter case, diffuse osteosclerosis and H-shaped vertebrae are most typical. Tuberculous spondylodiscitis is characterized by the location in the thoracic region, preferential involvement of anterior elements, relative sparing of intervertebral discs, and cold abscesses.

  6. Mast cell derived carboxypeptidase A3 is decreased among patients with advanced coronary artery disease.

    Science.gov (United States)

    Lewicki, Łukasz; Siebert, Janusz; Koliński, Tomasz; Piekarska, Karolina; Reiwer-Gostomska, Magdalena; Targoński, Radosław; Trzonkowski, Piotr; Marek-Trzonkowska, Natalia

    2018-03-07

    Coronary artery disease (CAD) affects milions of people and can result in myocardial infarction (MI). Previously, mast cells (MC) have been extensively investigated in the context of hypersensitivity, however as regulators of the local inflammatory response they can potentially contribute to CAD and/or its progression. The aim of the study was to assess if serum concentration of MC proteases: carboxypeptidase A3, cathepsin G and chymase 1 is associated with the extension of CAD and MI. The 44 patients with angiographically confirmed CAD (23 subjects with non-ST segment elevation MI [NSTEMI] and 21 with stable CAD) were analyzed. Clinical data were obtained as well serum concentrations of carboxypeptidase A3, cathepsin G and chymase 1 were also measured. Patients with single vessel CAD had higher serum concentration of carboxypeptidase than those with more advanced CAD (3838.6 ± 1083.1 pg/mL vs. 2715.6 ± 442.5 pg/mL; p = 0.02). There were no significant differences in levels of any protease between patients with stable CAD and those with NSTEMI. Patients with hypertension had ≈2-fold lower serum levels of cathepsin G than normotensive individuals (4.6 ± 0.9 pg/mL vs. 9.4 ± 5.8 pg/mL; p = 0.001). Cathepsin G levels were also decreased in sera of the current smokers as compared with non-smokers (3.1 ± 1.2 ng/mL vs. 5.8 ± 1.2 ng/mL, p = 0.02). 1. Decreased serum level of carboxypeptidase is a hallmark of more advanced CAD. 2. Lower serum levels of carboxypeptidase A3 and catepsin G are associated with risk factors of blood vessel damage suggesting a protective role of these enzymes in CAD.

  7. High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients.

    Science.gov (United States)

    Dawoodji, Amina; Chen, Ji-Li; Shepherd, Dawn; Dalin, Frida; Tarlton, Andrea; Alimohammadi, Mohammad; Penna-Martinez, Marissa; Meyer, Gesine; Mitchell, Anna L; Gan, Earn H; Bratland, Eirik; Bensing, Sophie; Husebye, Eystein S; Pearce, Simon H; Badenhoop, Klaus; Kämpe, Olle; Cerundolo, Vincenzo

    2014-09-01

    The mechanisms behind destruction of the adrenal glands in autoimmune Addison's disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the disease. In this article, we demonstrate highly frequent 21-hydroxylase-specific T cells detectable in 20 patients with Addison's disease. Using overlapping 18-aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8(+) and CD4(+) T cell responses in a large proportion of Addison's patients both ex vivo and after in vitro culture of PBLs ≤20 y after diagnosis. In a large proportion of patients, CD8(+) and CD4(+) 21-hydroxylase-specific T cells were very abundant and detectable in ex vivo assays. HLA class I tetramer-guided isolation of 21-hydroxylase-specific CD8(+) T cells showed their ability to lyse 21-hydroxylase-positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate that strong CTL responses to 21-hydroxylase often occur in vivo, and that reactive CTLs have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer. Copyright © 2014 by The American Association of Immunologists, Inc.

  8. A fatal case of immune hyperhemolysis with bone marrow necrosis in a patient with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Matthew S. Karafin

    2017-03-01

    Full Text Available In patients with sickle cell disease, hyperhemolysis is a rare but life-threatening complication of transfusion. In this case report, we describe a 61 year-old woman with hemoglobin sickle cell (SC disease and history of alloimmunization who developed hyperhemolysis associated with a transfusion. She was found to have a warm and a clinically-significant cold autoantibody. Severe anemia (Hb 2.7 g/dL with reticulocytopenia and thrombocytopenia prompted a bone marrow biopsy, which demonstrated extensive bone marrow necrosis. Despite treatment, the bone marrow failure did not improve and the patient died on hospital day 38. This case illustrates the potential risks of transfusion in a patient with sickle cell disease, especially one with previous hemolytic reactions. While uncommon, hyperhemolysis can cause death, in this case by extensive bone marrow necrosis. In patients with sickle cell disease, judicious use of red cell transfusions with phenotypically-matched units can diminish, but never completely abrogate, the risks associated with transfusion.

  9. Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Atsushi Tanaka

    2015-08-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs has opened up a new scientific frontier in medicine. This technology has made it possible to obtain pluripotent stem cells from individuals with genetic disorders. Because iPSCs carry the identical genetic anomalies related to those disorders, iPSCs are an ideal platform for medical research. The pathophysiological cellular phenotypes of genetically heritable heart diseases such as arrhythmias and cardiomyopathies, have been modeled on cell culture dishes using disease-specific iPSC-derived cardiomyocytes. These model systems can potentially provide new insights into disease mechanisms and drug discoveries. This review focuses on recent progress in cardiovascular disease modeling using iPSCs, and discusses problems and future perspectives concerning their use.

  10. Circulating T-cell subsets in Graves' disease: differences between patients with active disease and in remission after 131I-therapy

    International Nuclear Information System (INIS)

    Canonica, G.W.; Bagnasco, M.; Ferrini, S.; Biassoni, P.; Giordano, G.; Corte, G.

    1983-01-01

    In the present investigation some surface markers in peripheral blood T lymphocytes of patients with active Graves' disease and subjects in remission after 131 I-therapy have been studied. We confirmed low TG levels in untreated patients and normal values in treated subjects. Increased percentages of DR+, MLR4+ (activated T cells), and 5/9+ (inducer-helper) T cells were detected in patients with active disease, thus indicating the presence of activated T cells and suggesting increased levels of helper T cells. High percentages of MLR4+ and 5/9+, but normal levels of DR+ were found in 131 I-treated subjects. The different distribution of DR and MLR4 positivities on 5/9+ and 5+9-T cells confirm the different meaning of these two markers of the activation state. The imbalance of T-cell subsets found in 131 I-treated subjects and the normal values observed in patients with hyperthyroidism due to toxic adenoma indicate that hyperthyroidism per se is not sufficient to explain the T-cell alterations. The possible meaning of these findings is discussed with respect to previous hypotheses on the pathogenesis of Graves' disease

  11. p75 neurotrophin receptor positive dental pulp stem cells: new hope for patients with neurodegenerative disease and neural injury.

    Science.gov (United States)

    Dai, Jie-wen; Yuan, Hao; Shen, Shun-yao; Lu, Jing-ting; Zhu, Xiao-fang; Yang, Tong; Zhang, Jiang-fei; Shen, Guo-fang

    2013-08-01

    Neurodegenerative diseases and neural injury are 2 of the most feared disorders that afflict humankind by leading to permanent paralysis and loss of sensation. Cell based treatment for these diseases had gained special interest in recent years. Previous studies showed that dental pulp stem cells (DPSCs) could differentiate toward functionally active neurons both in vitro and in vivo, and could promote neuranagenesis through both cell-autonomous and paracrine neuroregenerative activities. Some of these neuroregenerative activities were unique to tooth-derived stem cells and superior to bone marrow stromal cells. However, DPSCs used in most of these studies were mixed and unfractionated dental pulp cells that contain several types of cells, and most were fibroblast cells while just contain a small portion of DPSCs. Thus, there might be weaker ability of neuranagenesis and more side effects from the fibroblast cells that cannot differentiate into neural cells. p75 neurotrophin receptor (p75NTR) positive DPSCs subpopulation was derived from migrating cranial neural crest cells and had been isolated from DPSCs, which had capacity of differentiation into neurons and repairing neural system. In this article, we hypothesize that p75NTR positive DPSCs simultaneously have greater propensity for neuronal differentiation and fewer side effects from fibroblast, and in vivo transptantation of autologous p75NTR positive DPSCs is a novel method for neuranagenesis. This will bring great hope to patients with neurodegenerative disease and neural injury.

  12. Evaluation of IgG4+ Plasma Cell Infiltration in Patients with Systemic Plasmacytosis and Other Plasma Cell-infiltrating Skin Diseases

    Directory of Open Access Journals (Sweden)

    Shintaro Takeoka

    2018-02-01

    Full Text Available Systemic plasmacytosis is a rare skin disorder characterized by marked infiltration of plasma cells in the dermis. IgG4-related disease is pathologically characterized by lymphoplasmacytic infiltration rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis, accompanied by elevated levels of serum IgG4. Reports of cases of systemic plasmacytosis with abundant infiltration of IgG4+ plasma cells has led to discussion about the relationship between systemic plasmacytosis and IgG4-related disease. This study examined IgG4+/IgG+ plasma cell ratios in 4 patients with systemic plasmacytosis and 12 patients with other skin diseases that show marked infiltration of plasma cells. Furthermore, we examined whether these cases met one of the pathological diagnostic criteria for IgG4-related disease (i.e. IgG4+/IgG plasma cells ratio of over 40%. Only one out of 4 patients with systemic plasmacytosis met the criterion. These results suggest that systemic plasmacytosis and IgG4-related disease are distinct diseases.

  13. Autologous blood stem-cell transplantation in patients with advanced Hodgkin's disease and prior radiation to the pelvic site

    International Nuclear Information System (INIS)

    Koerbling, M.H.; Holle, R.; Haas, R.; Knauf, W.; Doerken, B.H.; Ho, A.D.; Kuse, R.; Pralle, H.; Fliedner, T.M.; Hunstein, W.

    1990-01-01

    Patients with relapsed Hodgkin's disease who respond to salvage therapy are successfully treated with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologus bone marrow transplantation (ABMT). Because of heavy pretreatment including radiation to the pelvic site, marrow harvest was not feasible in those patients. We therefore used blood-derived hemopoietic precursor cells as an alternative stem-cell source to rescue them after superdose chemotherapy. Hemopoietic precursor cells were mobilized into the peripheral blood either by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem-cell concentration, or by continuous intravenous (IV) granulocyte-macrophage colony-stimulating factor (GM-CSF) administration. The median time to reach 1,000 WBC per microliter, 500 polymorphonuclear cells (PMN) per microliter, or 20,000 platelets per microliter was 10, 20.5, and 38 days, respectively, for 50% of all patients. The platelet counts of two patients never dropped below 20,000/microL following autologous blood stem-cell transplantation (ABSCT), whereas two other patients had to be supported with platelets for 75 and 86 days posttransplant until a stable peripheral platelet count of 20,000/microL was attained. Among the 11 assessable patients, seven are in unmaintained complete remission (CR) at a median follow-up of 318 days. This is a first report on a series of ABSCTs in patients with advanced Hodgkin's disease proving that, despite prior damage to the marrow site, the circulating stem-cell pool is still a sufficient source of hemopoietic precursor cells for stem-cell rescue

  14. Increased Numbers of NK Cells, NKT-Like Cells, and NK Inhibitory Receptors in Peripheral Blood of Patients with Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Ying Tang

    2013-01-01

    Full Text Available T cells and B cells participate in the pathogenesis of COPD. Currently, NK cells and NKT cells have gained increasing attention. In the present study, 19 COPD patients and 12 healthy nonsmokers (HNS were recruited, and their pulmonary function was assessed. The frequencies of CD3+ T, CD4+ T, CD8+ T, B, NK, and NKT-like cells were determined using flow cytometry. The frequencies of spontaneous and inducible IFN-γ+ or CD107a+ NK and NKT-like cells as well as activating or inhibitory receptors were also detected. The potential association of lymphocyte subsets with disease severity was further analyzed. Significantly decreased numbers of CD3+ and CD4+ T cells, and the CD4+/CD8+ ratio, but increased numbers of CD3−CD56+ NK and CD3+CD56+ NKT-like cells were observed in COPD patients compared to HNS. The frequencies of inducible IFN-γ-secreting NK and NKT-like cells were less in COPD patients. The frequencies of CD158a and CD158b on NK cells and CD158b on NKT-like cells were greater. The frequency of CD158b+ NK cells was negatively correlated with FEV1% prediction and FEV1/FVC. Our data indicate that COPD patients have immune dysfunction, and higher frequencies of inhibitory NK cells and NKT-like cells may participate in the pathogenesis of COPD.

  15. Activity of glucocerebrosidase in extracts of different cell types from type 1 Gaucher disease patients

    NARCIS (Netherlands)

    Sa Miranda, M. C.; Aerts, J. M.; Pinto, R.; Fontes, A.; de Lacerda, L. W.; van Weely, S.; Barranger, J.; Tager, J. M.

    1990-01-01

    Glucocerebrosidase activity in extracts of leukocytes, Epstein-Barr virus transformed lymphocytes and fibroblasts from Portuguese Type 1 Gaucher disease patients was studied. The residual glucocerebrosidase activity in all extracts from patients was less than 25% if measured in the presence of bile

  16. Optimization of folic acid, vitamin B-12, and vitamin B-6 supplements in pediatric patients with sickle cell disease

    NARCIS (Netherlands)

    van der Dijs, Fey P L; Fokkema, M Rebecca; Dijck-Brouwer, D A Janneke; Niessink, Bram; van der Wal, Thaliet I C; Schnog, John-John B; Duits, Ashley J; Muskiet, Fred D; Muskiet, Frits A J

    Using homocysteine as a functional marker, we determined optimal folic acid, vitamin B-12, and vitamin B-6 dosages in 21 pediatric sickle cell disease (SCD) patients (11 HbSS, 10 HbSC; 7-16 years). Daily supplements of folic acid (400, 700, or 1,000 mug), vitamin B-12 (1, 3, or 5 U.S. 1989 RDA), and

  17. Imaging manifestations of acquired elastopathy resembling pseudoxanthoma elasticum in patients with beta thalassaemia major and sickle cell disease

    International Nuclear Information System (INIS)

    Narayana, Harish; Cheng, Ken; Lau, Ken; Harish, Radhika; Bowden, Donald K.

    2016-01-01

    Development of an acquired systemic elastopathy resembling pseudoxanthoma elasticum in patients with chronic haemoglobinopathies such as beta thalassaemia major and sickle cell disease is well documented. There is paucity of any comprehensive literature on the radiological manifestations of this entity. This pictorial review aims to describe and illustrate the multi system and multi modality imaging findings of this condition.

  18. Long-chain PUFA in Granulocytes, Mononuclear Cells, and RBC in Patients With Cystic Fibrosis: Relation to Liver Disease

    DEFF Research Database (Denmark)

    Jorgensen, Marianne H.; Ott, Peter; Michaelsen, Kim F.

    2012-01-01

    -related liver disease were matched with 20 CF patients without. Blood samples were analysed for liver biochemistry and haematology. Granulocytes, mononuclear cells, and RBC were separated by density gradient centrifugation, and fatty acid composition was measured by gas chromatography. Hepatic ultrasound...

  19. Evaluation of antibody response to polysaccharide vaccine and switched memory B cells in pediatric patients with inflammatory bowel disease.

    Science.gov (United States)

    Fallahi, Gholamhossein; Aghamohammadi, Asghar; Khodadad, Ahmad; Hashemi, Mojtaba; Mohammadinejad, Payam; Asgarian-Omran, Hossein; Najafi, Mehri; Farhmand, Fatemeh; Motamed, Farzaneh; Soleimani, Khadije; Soheili, Habib; Parvaneh, Nima; Darabi, Behzad; Nasiri Kalmarzi, Rasoul; Pourhamdi, Shabnam; Abolhassani, Hassan; Mirminachi, Babak; Rezaei, Nima

    2014-01-01

    Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients. Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated. Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9±32.5 µg/mL vs 219.8±59.0 µg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed. A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.

  20. Increased IL-35 producing Tregs and CD19+IL-35+ cells are associated with disease progression in leprosy patients.

    Science.gov (United States)

    Tarique, Mohd; Saini, Chaman; Naqvi, Raza Ali; Khanna, Neena; Rao, D N

    2017-03-01

    The clinical forms of leprosy consist of a spectrum that reflects the host's immune response to the M. leprae; it provides an ideal model to study the host pathogen interaction and immunological dysregulation in humans. IL-10 and TGF-β producing Tregs are high in leprosy patients and responsible for immune suppression and M. leprae specific T cells anergy. In leprosy, involvement of IL-35 producing Tregs and Bregs remain unstudied. To study the role of IL-35 producing Tregs and Bregs in the human leprosy. Peripheral blood mononuclear cells from leprosy patients were isolated and stimulated with M. leprae antigen (MLCwA) for 48h. Intracellular cytokine IL-35 was evaluated in CD4 + CD25 + Tregs, CD19 + cells by FACS. Expression of PD-1 on CD4 + CD25 + Tregs, CD19 + cells and its ligand (PD-L1) on B cells, CD11c cells were evaluated by flow cytometry (FACS). Serum IL-35 level was estimated by ELISA. The frequency of IL-35 producing Tregs and Bregs cells were found to be high in leprosy patients (pleprosy patients. This study point out a shift in our understanding of the immunological features that mediate and regulate the immune suppression and the disease progression in leprosy patients with a new paradigm (IL-35 producing Tregs and Bregs) that is beyond TGF-β and IL-10 producing Treg cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Serum progranulin irrelated with Breg cell levels, but elevated in RA patients, reflecting high disease activity.

    Science.gov (United States)

    Chen, Jiaxi; Li, Shuang; Shi, Jianfeng; Zhang, Lili; Li, Jun; Chen, Shiyong; Wu, Chunlong; Shen, Bo

    2016-03-01

    Soluble progranulin (PGRN) is known to directly regulate regulatory T cells; however, whether PGRN levels are elevated in patients with rheumatoid arthritis and affect the regulatory subsets of B cells remain unknown. In this study, a total of 80 RA patients and 60 healthy controls were studied. Serum progranulin levels were determined using enzyme-linked immune-sorbent assay. A receiver operating characteristic (ROC) curve was used to evaluate the feasibility of serum PGRN as a biomarker for distinguishing patients with RA. CD19(+)CD5(+)GrB(+) B cells were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs). Serum progranulin levels in RA patients (median, 59.4 ng/mL) and in RA patients DAS28 > 5.1 (median, 71.98 ng/mL) were much higher than those in normal controls (median, 46.3 ng/mL; P progranulin levels was 0.705 for RA versus normal controls and the area under the ROC curve for progranulin levels in RA patients DAS28 > 5.1 was 0.977 versus normal controls (P progranulin and DAS28, CRP, ESR were all positively correlated in RA patients (P 0.05). Our findings indicated that induction of PGRN expression may play a role in RA immune reaction and PGRN levels could be a useful biomarker in RA inflammatory response, but irrelated with Breg cell levels.

  2. Tuberculous spondylodiscitis in a patient with a sickle-cell disease: CT findings

    OpenAIRE

    Krupniewski, Leszek; Palczewski, Piotr; Gołębiowski, Marek; Kosińska-Kaczyńska, Katarzyna

    2012-01-01

    Summary Background: Although sickle-cell anemia (SCA) is common in black Americans, Sub-Saharan Africa and in the Mediterranean area, the disease is rare in the temperate climate zone. The manifestations of the disease are related mainly to the production of abnormal hemoglobin that leads to organ ischemia and increased susceptibility to infection caused by functional asplenia. Case Report: The authors present CT findings in a 39-year-old black woman diagnosed due to abdominal pain, lymphaden...

  3. Priapism in paediatric patients with sickle cell disease - a report of ...

    African Journals Online (AJOL)

    Results: Of the 185 SCD cases, three (1.6%) had priapism. They were adolescents aged 17years, 11years and 10 years 9months respectively. Two patients had never attended a sickle cell clinic, never been on routine drugs nor received advice on oral liberal fluids intake. One patient had stuttering priapism, 24hours before ...

  4. Lack of functional relevance of isolated cell damage in transplants of Parkinson's disease patients

    DEFF Research Database (Denmark)

    Cooper, Oliver; Astradsson, Arnar; Hallett, Penny

    2009-01-01

    Postmortem analyses from clinical neural transplantation trials of several subjects with Parkinson's disease revealed surviving grafted dopaminergic neurons after more than a decade. A subset of these subjects displayed isolated dopaminergic neurons within the grafts that contained Lewy body......-like structures. In this review, we discuss why this isolated cell damage is unlikely to affect the overall graft function and how we can use these observations to help us to understand age-related neurodegeneration and refine our future cell replacement therapies....

  5. Factors associated with disease-specific survival of patients with non-small cell lung cancer.

    Science.gov (United States)

    Souza, Mirian Carvalho de; Cruz, Oswaldo Gonçalves; Vasconcelos, Ana Glória Godoi

    2016-01-01

    Lung cancer is a global public health problem and is associated with high mortality. Lung cancer could be largely avoided by reducing the prevalence of smoking. The objective of this study was to analyze the effects of social, behavioral, and clinical factors on the survival time of patients with non-small cell lung cancer treated at Cancer Hospital I of the José Alencar Gomes da Silva National Cancer Institute, located in the city of Rio de Janeiro, Brazil, between 2000 and 2003. This was a retrospective hospital cohort study involving 1,194 patients. The 60-month disease-specific survival probabilities were calculated with the Kaplan-Meier method for three stage groups. The importance of the studied factors was assessed with a hierarchical theoretical model after adjustment by Cox multiple regression. The estimated 60-month specific-disease lethality rate was 86.0%. The 60-month disease-specific survival probability ranged from 25.0% (stages I/II) to 2.5% (stage IV). The performance status, the intention to treat, and the initial treatment modality were the major prognostic factors identified in the study population. In this cohort of patients, the disease-specific survival probabilities were extremely low. We identified no factors that could be modified after the diagnosis in order to improve survival. Primary prevention, such as reducing the prevalence of smoking, is still the best method to reduce the number of people who will suffer the consequences of lung cancer. O câncer de pulmão é um problema de saúde pública global e é associado a elevada mortalidade. Ele poderia ser evitado em grande parte com a redução da prevalência do tabagismo. O objetivo deste estudo foi analisar os efeitos de fatores sociais, comportamentais e clínicos sobre o tempo de sobrevida de pacientes com câncer de pulmão de células não pequenas atendidos, entre 2000 e 2003, no Hospital do Câncer I do Instituto Nacional de Câncer José Alencar Gomes da Silva, localizado na

  6. Environmental Influences on Daily Emergency Admissions in Sickle-Cell Disease Patients

    Science.gov (United States)

    Mekontso Dessap, Armand; Contou, Damien; Dandine-Roulland, Claire; Hemery, François; Habibi, Anoosha; Charles-Nelson, Anaïs; Galacteros, Frederic; Brun-Buisson, Christian; Maitre, Bernard; Katsahian, Sandrine

    2014-01-01

    Abstract Previous reports have suggested a role for weather conditions and air pollution on the variability of sickle cell disease (SCD) severity, but large-scale comprehensive epidemiological studies are lacking. In order to evaluate the influence of air pollution and climatic factors on emergency hospital admissions (EHA) in SCD patients, we conducted an 8-year observational retrospective study in 22 French university hospitals in Paris conurbation, using distributed lag non-linear models, a methodology able to flexibly describe simultaneously non-linear and delayed associations, with a multivariable approach. During the 2922 days of the study, there were 17,710 EHA, with a mean daily number of 6.1 ± 2.8. Most environmental factors were significantly correlated to each other. The risk of EHA was significantly associated with higher values of nitrogen dioxide, atmospheric particulate matters, and daily mean wind speed; and with lower values of carbon monoxide, ozone, sulfur dioxide, daily temperature (minimal, maximal, mean, and range), day-to-day mean temperature change, daily bright sunshine, and occurrence of storm. There was a lag effect for 12 of 15 environmental factors influencing hospitalization rate. Multivariate analysis identified carbon monoxide, day-to-day temperature change, and mean wind speed, along with calendar factors (weekend, summer season, and year) as independent factors associated with EHA. In conclusion, most weather conditions and air pollutants assessed were correlated to each other and influenced the rate of EHA in SCD patients. In multivariate analysis, lower carbon monoxide concentrations, day-to-day mean temperature drop and higher wind speed were associated with increased risk of EHA. PMID:25546672

  7. Defective proximal tubular function in a patient with I-cell disease.

    NARCIS (Netherlands)

    Bocca, G.; Monnens, L.A.H.

    2003-01-01

    A girl with a proven diagnosis of I-cell disease is presented. Proximal tubular dysfunction was characterized by increased excretion of low molecular proteins, aminoaciduria, hyperphosphaturia, and high/slightly increased urinary calcium. The concentration of 1,25-dihydroxycalciferol in serum was

  8. The composition of T cell subtypes in duodenal biopsies are altered in coeliac disease patients

    DEFF Research Database (Denmark)

    Vagner Steenholt, Janni; Nielsen, Christian; Baudewijn, Leen

    2017-01-01

    One of the hallmarks of Celiac disease (CD) is intraepithelial lymphocytosis in the small intestine. Until now, investigations to characterize the T cell subpopulations within the epithelial layer have not discriminated between the heterodimeric co-receptor molecule, CD8αβ, and the possibly...

  9. Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

    NARCIS (Netherlands)

    Nur, Erfan; Kim, Yu-Sok; Truijen, Jasper; van Beers, Eduard J.; Davis, Shyrin C. A. T.; Brandjes, Dees P.; Biemond, Bart J.; van Lieshout, Johannes J.

    2009-01-01

    Sickle cell disease (SCD) is associated with a high incidence of ischemic stroke. SCD is characterized by hemolytic anemia, resulting in reduced nitric oxide-bioavailability, and by impaired cerebrovascular hemodynamics. Cerebrovascular CO2 responsiveness is nitric oxide dependent and has been

  10. Disease-causing mitochondrial heteroplasmy segregated within induced pluripotent stem cell clones derived from a patient with MELAS.

    Science.gov (United States)

    Folmes, Clifford D L; Martinez-Fernandez, Almudena; Perales-Clemente, Ester; Li, Xing; McDonald, Amber; Oglesbee, Devin; Hrstka, Sybil C; Perez-Terzic, Carmen; Terzic, Andre; Nelson, Timothy J

    2013-07-01

    Mitochondrial diseases display pathological phenotypes according to the mixture of mutant versus wild-type mitochondrial DNA (mtDNA), known as heteroplasmy. We herein examined the impact of nuclear reprogramming and clonal isolation of induced pluripotent stem cells (iPSC) on mitochondrial heteroplasmy. Patient-derived dermal fibroblasts with a prototypical mitochondrial deficiency diagnosed as mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) demonstrated mitochondrial dysfunction with reduced oxidative reserve due to heteroplasmy at position G13513A in the ND5 subunit of complex I. Bioengineered iPSC clones acquired pluripotency with multilineage differentiation capacity and demonstrated reduction in mitochondrial density and oxygen consumption distinguishing them from the somatic source. Consistent with the cellular mosaicism of the original patient-derived fibroblasts, the MELAS-iPSC clones contained a similar range of mtDNA heteroplasmy of the disease-causing mutation with identical profiles in the remaining mtDNA. High-heteroplasmy iPSC clones were used to demonstrate that extended stem cell passaging was sufficient to purge mutant mtDNA, resulting in isogenic iPSC subclones with various degrees of disease-causing genotypes. On comparative differentiation of iPSC clones, improved cardiogenic yield was associated with iPSC clones containing lower heteroplasmy compared with isogenic clones with high heteroplasmy. Thus, mtDNA heteroplasmic segregation within patient-derived stem cell lines enables direct comparison of genotype/phenotype relationships in progenitor cells and lineage-restricted progeny, and indicates that cell fate decisions are regulated as a function of mtDNA mutation load. The novel nuclear reprogramming-based model system introduces a disease-in-a-dish tool to examine the impact of mutant genotypes for MELAS patients in bioengineered tissues and a cellular probe for molecular features of individual

  11. Combined analysis of circulating epithelial cells and serum thyroglobulin for distinguishing disease status of the patients with papillary thyroid carcinoma.

    Science.gov (United States)

    Lin, Hung-Chih; Liou, Miaw-Jene; Hsu, Hsung-Ling; Hsieh, Jason Chia-Hsun; Chen, Yi-An; Tseng, Ching-Ping; Lin, Jen Der

    2016-03-29

    Papillary thyroid carcinoma (PTC) accounts for about 80% of the cases in thyroid cancer. Routine surveillance by serum thyroglobulin (Tg) and medical imaging is the current practice to monitor disease progression of the patients. Whether enumeration of circulating epithelial cells (CECs) helps to define disease status of PTC patients was investigated. CECs were enriched from the peripheral blood of the healthy control subjects (G1, n = 17) and the patients at disease-free status (G2, n = 26) or with distant metastasis (G3, n = 22). The number of CECs expressing epithelial cell adhesion molecule (EpCAM) or thyroid-stimulating hormone receptor (TSHR) was determined by immunofluorescence microscopy analyses. The medium number of EpCAM+-CECs was 6 (interquartile range 1-11), 12 (interquartile range 7-16) and 91 (interquartile range 31-206) cells/ml of blood for G1, G2 and G3, respectively. EpCAM+-CEC counts were significantly higher in G3 than in G1 (p interquartile range 3-13), 16 (interquartile range 10-24) and 100 (interquartile range 31-226) cells/ml of blood for G1, G2 and G3, respectively. The TSHR+-CEC counts also distinguished G3 from G1 (p < 0.05) and G2 (p < 0.05). With an appropriate cut off value of CEC count, the disease status for 97.9% (47/48) of the cases was clearly defined. Notably, the metastatic disease for all patients in G3 (22/22) was revealed by combined analysis of serum Tg and CEC. This study implicates that CEC testing can supplement the current standard methods for monitoring disease status of PTC.

  12. Concurrent chemoradiotherapy for limited-disease small cell lung cancer in elderly patients aged 75 years or older

    International Nuclear Information System (INIS)

    Shimizu, Toshio; Sekine, Ikuo; Sumi, Minako

    2007-01-01

    The optimal treatment for limited-disease small cell lung cancer (LD-SCLC) in patients aged 75 years or older remains unknown. Elderly patients with LD-SCLC who were treated with chemoradiotherapy were retrospectively reviewed to evaluate their demographic characteristics and the treatment delivery, drug toxicities and antitumor efficacy. Of the 94 LD-SCLC patients treated with chemotherapy and thoracic radiotherapy at the National Cancer Center Hospital between 1998 and 2003, seven (7.4%) were 75 years of age or older. All of the seven patients were in good general condition, with a performance status of 0 or 1. Five and two patients were treated with early and late concurrent chemoradiotherapy, respectively. While the four cycles of chemotherapy could be completed in only four patients, the full dose of radiotherapy was completed in all of the patients. Grade 4 neutropenia and thrombocytopenia were noted in seven and three patients, respectively. Granulocyte-colony stimulating factor support was used in five patients, red blood cell transfusion was administered in two patients and platelet transfusion was administered in one patient. Grade 3 or more severe esophagitis, pneumonitis and neutropenic fever developed in one, two and three patients, respectively, and one patient died of radiation pneumonitis. Complete response was achieved in six patients and partial response in one patient. The median survival time was 24.7 months, with three disease-free survivors for more than 5 years. Concurrent chemoradiotherapy promises to provide long-term benefit with acceptable toxicity for selected patients of LD-SCLC aged 75 years or older. (author)

  13. Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease

    DEFF Research Database (Denmark)

    Cooper, Oliver; Seo, Hyemyung; Andrabi, Shaida

    2012-01-01

    , or the LRRK2 kinase inhibitor GW5074. Analysis of mitochondrial responses in iPSC-derived neural cells from PD patients carrying different mutations provides insight into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress...... of reactive oxygen species, mitochondrial respiration, proton leakage, and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial dysfunction in iPSC-derived neural cells from familial PD patients and at-risk individuals could be rescued with coenzyme Q(10), rapamycin...

  14. Cell Therapy in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Hoda Madani

    2014-05-01

    Full Text Available   Recently, cell therapy has sparked a revolution in ischemic heart disease that will in the future help clinicians to cure patients. Earlier investigations in animal models and clinical trials have suggested that positive paracrine effects such as neoangiogenesis and anti-apoptotic can improve myocardial function. In this regard the Royan cell therapy center designed a few trials in collaboration with multi hospitals such as Baqiyatallah, Shahid Lavasani, Tehran Heart Center, Shahid rajaee, Masih daneshvari, Imam Reza, Razavi and Sasan from 2006. Their results were interesting. However, cardiac stem cell therapy still faces great challenges in optimizing the treatment of patients. Keyword: Cardiovascular disease, Cell therapy.  

  15. Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic lupus erythematosus patients.

    Science.gov (United States)

    Carrion, F; Nova, E; Ruiz, C; Diaz, F; Inostroza, C; Rojo, D; Mönckeberg, G; Figueroa, F E

    2010-03-01

    Mesenchymal stem cells (MSCs) exert suppressive effects in several disease models including lupus prone mice. However, autologous MSC therapy has not been tested in human systemic lupus erythematosus (SLE). We evaluate the safety and efficacy of bone marrow (BM)-derived MSCs in two SLE patients; the suppressor effect of these cells in-vitro and the change in CD4+CD25+FoxP3+ T regulatory (Treg) cells in response to treatment. Two females (JQ and SA) of 19 and 25 years of age, fulfilling the 1997 American College of Rheumatology (ACR) criteria for SLE were infused with autologous BM-derived MSCs. Disease activity indexes and immunological parameters were assessed at baseline, 1, 2, 7 and 14 weeks. Peripheral blood lymphocyte (PBL) subsets and Treg cells were quantitated by flow cytometry, and MSCs tested for in-vitro suppression of activation and proliferation of normal PBLs. No adverse effects or change in disease activity indexes were noted during 14 weeks of follow-up, although circulating Treg cells increased markedly. Patient MSCs effectively suppressed in-vitro PBL function. However, JQ developed overt renal disease 4 months after infusion. MSC infusion was without adverse effects, but did not modify initial disease activity in spite of increasing CD4+CD25+FoxP3+ cell counts. One patient subsequently had a renal flare. We speculate that the suppressive effects of MSC-induced Treg cells might be dependent on a more inflammatory milieu, becoming clinically evident in patients with higher degrees of disease activity.

  16. FOXP3+ T Regulatory Cell Modifications in Inflammatory Bowel Disease Patients Treated with Anti-TNFα Agents

    Directory of Open Access Journals (Sweden)

    Luisa Guidi

    2013-01-01

    Full Text Available Treg modulation has been hypothesized as one of the mechanisms by which antitumor necrosis factor α (TNFα agents exert their action in rheumatoid arthritis (RA and inflammatory bowel disease (IBD. However, data in IBD are still conflicting. We evaluated CD4+CD25+FOXP3+ (Tregs by flow cytometry in peripheral blood from 32 adult IBD patient before (T0 and after the induction of anti-TNFα therapy (T1. Eight healthy controls (HCs were included. We also evaluated the number of FOXP3+ cells in the lamina propria (LP in biopsies taken in a subset of patients and controls. Treg frequencies were significantly increased in peripheral blood from our patients after anti-TNFα therapy compared to T0. T1 but not T0 levels were higher than HC. The increase was detectable only in clinical responders to the treatment. A negative correlation was found among delta Treg levels and the age of patients or disease duration and with the activity score of Crohn’s disease (CD. No significant differences were found in LP FOXP3+ cells. Our data suggest the possibility that in IBD patients the treatment with anti-TNFα may affect Treg percentages and that Treg modifications may correlate with clinical response, but differently in early versus late disease.

  17. Impact of an emergency department pain management protocol on the pattern of visits by patients with sickle cell disease.

    Science.gov (United States)

    Givens, Melissa; Rutherford, Cynthia; Joshi, Girish; Delaney, Kathleen

    2007-04-01

    This study explores how implementation of pain management guidelines in concert with clinic case management affected emergency department (ED) utilization, clinic visits, and hospital admissions for patients with sickle cell disease. A pain management guideline that eliminated meperidine and encouraged timely use of morphine or hydromorphone for pain control in sickle cell crisis was introduced as a quality improvement project. This study is a retrospective review of ED visits, clinic visits, and admissions from 1 year before and 3 years after the guideline implementation. Working with the ED, the Hematology Clinic began to proactively seek the return of their patients for clinic follow-up. A formal case management program for sickle cell patients was initiated in June 2003. A total of 1584 visits by 223 patients were collected, 1097 to the ED and 487 to the Hematology Clinic. Total hospital visits did not change significantly in any of the 4 years, p > 0.10 for each comparison. Total ED visits decreased significantly over the 4-year study period (p study period, p = 0.001. Although total admissions per hospital visit did not change, the proportion of ED visits that resulted in admission in year 1 (29%) was significantly lower than the proportion admitted in year 2 (43%), p = 0.04. A pain protocol using morphine or hydromorphone coupled with increased access to outpatient clinics decreased ED visits, hospitalizations, and increased utilization of a more stable primary care clinic setting by patients with sickle cell disease.

  18. Red blood cell rheology in patients with chronic venous disease (CVD)

    NARCIS (Netherlands)

    Chwała, Maciej; Spannbauer, Anna; Teległów, Aneta; Cencora, Andrzej; Marchewka, Anna; Hardeman, Max R.; Dabrowski, Zbigniew

    2009-01-01

    Rheological studies concerning aggregation and elongation of erythrocytes were carried out in 21 patients (mean age 56 years) with chronic venous disease (CVD) and 10 (mean age 45 years) healthy control subjects, with the use of a LORCA device. Higher values of parameters characterizing both

  19. CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients

    DEFF Research Database (Denmark)

    Fløyel, Tina; Brorsson, Caroline; Nielsen, Lotte B

    2014-01-01

    expression and increased insulin secretion. Additionally, islets from Ctsh(-/-) mice contained less insulin than islets from WT mice. Importantly, the TT genotype was associated with higher daily insulin dose and faster disease progression in newly diagnosed T1D patients, indicating agreement between...

  20. Subarachnoid hemorrhage as complication of phenylephrine injection for the treatment of ischemic priapism in a sickle cell disease patient.

    Science.gov (United States)

    Davila, Hugo H; Parker, Justin; Webster, J Christopher; Lockhart, Jorge L; Carrion, Rafael E

    2008-04-01

    Ischemic priapism (IP) is a urologic condition, which necessitates prompt management. Intracavernosal injection of phenylephrine is a usual treatment modality utilized for the management of these patients. Aim. We present a case of subarachnoid hemorrhage following intracavernosal injection of phenylephrine for IP in a patient with sickle cell disease. We analyzed the degree of subarachnoid hemorrhage in our patient after intracavernosal injection of phenylephrine. The patient had an acute rise in blood pressure during corporal irrigation. This was followed by the onset of severe headache. Computed tomography (CT) scan confirmed the diagnosis of a subarachnoid hemorrhage. Subarachnoid hemorrhage associated with intracavernosal injection of phenylephrine. Result. A 23-year-old African American male with a history of sickle cell disease presented with a painful penile erection. The patient was started on intravenous fluids, oxygen by nasal canula, and analgesic medication. After this, a blood gas was obtained from his left corpora cavernosa. This was followed by normal saline irrigation and injection of phenylephrine. The patient complained of a sudden, severe "terrible headache" immediately following the last injection, and noncontrast CT scan of the head was obtained and a subarachnoid hemorrhage was noted. The patient was admitted for observation and no significant changes were noted. Intracavernosal injection of phenylephrine for the management of IP can be associated with several possible complications. We present our single case complicated with the formation of a subarachnoid hemorrhage. The patient was treated conservatively and had no long-term neurologic sequelae. Davila HH, Parker J, Webster JC, Lockhart JL, and Carrion RE. Subarachnoid hemorrhage as complication of phenylephrine injection for the treatment of ischemic priapism in a sickle cell disease patient.

  1. Establishment of induced pluripotent stem cell line (ZZUi010-A from an Alzheimer's disease patient carrying an APP gene mutation

    Directory of Open Access Journals (Sweden)

    Zhilei Wang

    2017-12-01

    Full Text Available Alzheimer's disease (AD is one of the most common neurodegenerative disorders. Previous studies have identified mutations in several genes, such as amyloid precursor protein (APP, presenilin-1 (PSEN1, and presenilin-2 (PSEN2, in patients with early-onset (<65 years familial AD. Recently, a patient with an APP gene mutation was identified; the dermal fibroblasts of the patient were obtained and a line of induced pluripotent stem cells (iPSCs was successfully generated using the Sendai-virus (SeV delivery system. The iPSC line will be useful for further study of the pathomechanism and drug screening for AD.

  2. Clinical Study on Patients with Renal-Cell Carcinoma Accompanied with Von Hippel Lindau Disease Treated with Radiofrequency Ablation

    OpenAIRE

    波越, 朋也; 島本, 力; 辛島, 尚; 亀井, 麻依子; 福原, 秀雄; 深田, 聡; 佐竹, 宏文; 蘆田, 真吾; 山崎, 一郎; 鎌田, 雅行; 井上, 啓史; 山西, 伴明; 小川, 恭弘; 伊藤, 悟志; 執印, 太郎

    2014-01-01

    We report 12 renal cell carcinomas in 6 patients with Von Hippel-Lindau (VHL) disease treated with radiofrequency ablation (RFA). The mean age of the patients was 46 (range 38-53) years (male : 4, female : 2). Computed tomography (CT)-guided transcutaneous RFA was performed under conscious sedation with local anesthetics. The mean size of the tumors was 2.4 (range 0.7-8.1) cm. Nine of the 12 tumors (75%) were locally well controlled. However, 3 tumors in 2 patients developed visceral metastas...

  3. Detection of cerebrovascular disease in patients with sickle cell disease using transcranial Doppler sonography: correlation with MRI, MRA and conventional angiography

    Energy Technology Data Exchange (ETDEWEB)

    Verlhac, S. [Service de Radiologie, Centre Hospitalier Intercommunal, 94 - Creteil (France); Bernaudin, F. [Service de Pediatrie, Centre Hospitalier Intercommunal, 94 - Creteil (France); Tortrat, D. [Association Claude Bernard, 75 - Paris (France); Brugieres, P. [Service de Neuroradiologie, Hopital Henri Mondor, 94 - Creteil (France); Mage, K. [Service de Radiologie, Centre Hospitalier Intercommunal, 94 - Creteil (France); Gaston, A. [Service de Neuroradiologie, Hopital Henri Mondor, 94 - Creteil (France); Reinert, P. [Service de Pediatrie, Centre Hospitalier Intercommunal, 94 - Creteil (France)

    1995-11-01

    A prospective study of 58 patients with sickle cell disease (SCD) by transcranial Doppler sonography (TCD) included both MRI and MRA in patients over 7 years of age and those with abnormal TCD. Arteriography was performed in cases where a stenosis was suspected on TCD. Middle cerebral artery (MCA) and basilar artery (BA) velocities were significantly higher in the sickle cell hemoglobin SS group than in the hemoglobin SC group. Patients with a MCA mean velocity of over 1.90 m/s had stenoses found by arteriography. Patients with unilaterally undetectable MCA flow had experienced a stroke and MCA thrombosis was confirmed at MRA and arteriography. We concluded that TCD is valuable in detecting arterial stenosis in SCD and will lead to consideration of these patients for intensive therapy, such as bone marrow transplantation (BMT) or transfusion regimes. (orig.)

  4. Detection of cerebrovascular disease in patients with sickle cell disease using transcranial Doppler sonography: correlation with MRI, MRA and conventional angiography

    International Nuclear Information System (INIS)

    Verlhac, S.; Bernaudin, F.; Tortrat, D.; Brugieres, P.; Mage, K.; Gaston, A.; Reinert, P.

    1995-01-01

    A prospective study of 58 patients with sickle cell disease (SCD) by transcranial Doppler sonography (TCD) included both MRI and MRA in patients over 7 years of age and those with abnormal TCD. Arteriography was performed in cases where a stenosis was suspected on TCD. Middle cerebral artery (MCA) and basilar artery (BA) velocities were significantly higher in the sickle cell hemoglobin SS group than in the hemoglobin SC group. Patients with a MCA mean velocity of over 1.90 m/s had stenoses found by arteriography. Patients with unilaterally undetectable MCA flow had experienced a stroke and MCA thrombosis was confirmed at MRA and arteriography. We concluded that TCD is valuable in detecting arterial stenosis in SCD and will lead to consideration of these patients for intensive therapy, such as bone marrow transplantation (BMT) or transfusion regimes. (orig.)

  5. Specific and Nonspecific B-Cell Function in the Small Intestines of Patients with Whipple's Disease

    Science.gov (United States)

    Geelhaar, Anika; Moos, Verena; Schinnerling, Katina; Allers, Kristina; Loddenkemper, Christoph; Fenollar, Florence; LaScola, Bernard; Raoult, Didier; Schneider, Thomas

    2010-01-01

    Whipple's disease is a chronic multisystemic infection caused by Tropheryma whipplei that is characterized by arthritis, weight loss, and diarrhea. The immunological defects in the duodenal mucosa, the site of major replication of the agent underlying the pathogenesis of Whipple's disease, are poorly understood. Mucosal immunoglobulins are essential for the defense against intestinal pathogens; therefore, we analyzed the B-cell response in duodenal specimens and sera of Whipple's disease patients. Whereas systemic immunoglobulin production was affected only marginally, duodenal biopsy specimens of Whipple's disease patients contained reduced numbers of immunoglobulin-positive plasma cells and secreted less immunoglobulin compared to healthy controls but showed a weak secretory IgA response toward T. whipplei. This T. whipplei-specific intestinal immune response was not observed in controls. Thus, we were able to demonstrate that general mucosal immunoglobulin production in Whipple's disease patients is impaired. However, this deficiency does not completely abolish T. whipplei-specific secretory IgA production that nonetheless does not protect from chronic infection. PMID:20696822

  6. Orbital wall infarction mimicking periorbital cellulitis in a patient with sickle cell disease

    International Nuclear Information System (INIS)

    Ozkavukcu, Esra; Fitoz, Suat; Erden, Ilhan; Yagmurlu, Banu; Ciftci, Ergin; Ertem, Mehmet

    2007-01-01

    Orbital wall infarction and subperiosteal haematomas are unusual manifestations of sickling disorders. Here we report an 11-year-old girl with sickle cell anaemia having multiple skull infarctions including the orbital bony structures associated with subperiosteal haematomas. The diagnosis was made by MRI, which showed bone marrow changes and associated haemorrhagic collections. The patient was successfully managed without surgical intervention. (orig.)

  7. [Clinical study on patients with renal-cell carcinoma accompanied with Von Hippel-Lindau disease treated with radiofrequency ablation].

    Science.gov (United States)

    Nao, Tomoya; Shimamoto, Tsutomu; Karashima, Takashi; Kamei, Maiko; Fukuhara, Hideo; Fukata, Satoshi; Satake, Hirofumi; Ashida, Shingo; Yamasaki, Ichiro; Kamata, Masayuki; Inoue, Keiji; Yamanishi, Tomoaki; Ogawa, Yasuhiro; Ito, Satoshi; Shuin, Taro

    2014-09-01

    We report 12 renal cell carcinomas in 6 patients with Von Hippel-Lindau (VHL) disease treated with radiofrequency ablation (RFA). The mean age of the patients was 46 (range 38-53) years (male : 4, female : 2). Computed tomography (CT)-guided transcutaneous RFA was performed under conscious sedation with local anesthetics. The mean size of the tumors was 2.4 (range 0.7-8.1) cm. Nine of the 12 tumors (75%) were locally well controlled. However, 3 tumors in 2 patients developed visceral metastases after RFA. While minimal flank pain, nausea, perinephritic hematoma and lumbago were observed, there was no major complication during or after the procedure. The therapy with CT-guided transcutaneous RFA is efficient and minimal invasive for renal cell carcinoma in patients with VHL, leading to preservation of renal function.

  8. Prognostic factors for patients with inoperable non-small cell lung cancer, limited disease

    International Nuclear Information System (INIS)

    Kaasa, S.; Mastekaasa, A.; Lund, E.

    1989-01-01

    In a prospective controlled clinical trial, 102 patients with inoperable non-small lung cancer (NSCLC), limited disease, stage II and III were treated with combination chemotherapy, cisplatin 70 mg/m 2 i.v. on day one and etoposide 100 mg/m 2 i.v. on day one, and etoposide 200 mg/m 2 orally on days 2 and 3, or radiotherapy given in 15 fractions of 2.8 Gy with two anterior/posterior fields during a period of three weeks. The patients completed a validated self-administered questionnaire before the start of treatment that assessed their psychosocial well-being, disease-related symptoms, personal functioning, and every day activity. These subjective varibles were evaluated together with treatment modality, WHO performance status, weight loss, and stage of disease, with regard to their value in predicting survival. Univariate survival analyses were undertaken for each individual factor, median survival was calculated according to life-table analyses. A step-wise multiple regression analysis was used to measure the prognostic value of the various factors. In the univariate analysis, general symptons (p=0.0006) psychosocial well-being (p=0.0002) and stage of disease (p=0.007) were the best predictive factors. In the multiple regression analyses the subjective variables, general symptons (p<0.01) and psychosocial well-being (p<0.05) were shown to have the best predictive value for the patients' survival. (author). 20 refs.; 4 figs.; 3 tabs

  9. MR marrow signs of iron overload in transfusion-dependent patients with sickle cell disease

    International Nuclear Information System (INIS)

    Levin, T.L.; Sheth, S.S.; Hurlet, A.; Comerci, S.C.; Ruzal-Shapiro, C.; Piomelli, S.; Berdon, W.E.

    1995-01-01

    Magnetic resonance (MR) marrow signal in the axial and appendicular skeleton of 13 transfusion-dependent and chelated pediatric patients with sickle cell anemia (SSD) was compared with marrow signal in six non-transfusion-dependent patients with SSD. Hepatic, pancreatic, and renal MR signal were also evaluated. Indication for hypertransfusion therapy was primarily prior history of stroke. Transfusion-dependent patients had evidence of iron deposition throughout the imaged marrow and the liver, despite deferoxamine chelation therapy. Non-transfusion-dependent patients did not demonstrate grossly apparent signs of iron overload. Red marrow restoration was present in the spine, pelvis, and long bones and, in some patients, within the epiphyses. Marrow edema secondary to vaso-occlusive crises was evident in the metaphyses and diaphyses of long bones in areas of both red and fatty marrow and was best seen using fat-saturated T2-weighted imaging techniques. (orig.). With 4 figs., 2 tabs

  10. Multicenter COMPACT study of COMplications in patients with sickle cell disease and utilization of iron chelation therapy.

    Science.gov (United States)

    Jordan, Lanetta; Adams-Graves, Patricia; Kanter-Washko, Julie; Oneal, Patricia A; Sasane, Medha; Vekeman, Francis; Bieri, Christine; Magestro, Matthew; Marcellari, Andrea; Duh, Mei Sheng

    2015-03-01

    Over the past few decades, lifespans of sickle cell disease (SCD) patients have increased; hence, they encounter multiple complications. Early detection, appropriate comprehensive care, and treatment may prevent or delay onset of complications. We collected longitudinal data on sickle cell disease (SCD) complication rates and associated resource utilization relative to blood transfusion patterns and iron chelation therapy (ICT) use in patients aged ≥16 years to address a gap in the literature. Medical records of 254 SCD patients ≥16 years were retrospectively reviewed at three US tertiary care centers. We classified patients into cohorts based on cumulative units of blood transfused and ICT history: ICT (Cohort 1 [C1]), ≥15 units, no ICT (Cohort 2 [C2]), and ≥15 units with ICT (Cohort 3 [C3]). We report SCD complication rates per patient per year; cohort comparisons use rate ratios (RRs). Cohorts had 69 (C1), 91 (C2), and 94 (C3) patients. Pain led to most hospitalizations (76%) and emergency department (ED) (82%) visits. Among transfused patients (C2+C3), those receiving ICT were less likely to experience SCD complications than those who did not (RR [95% CI] C2 vs. C3: 1.33 [1.25-1.42]). Similar trends (RR [95% CI]) were observed in ED visits and hospitalizations associated with SCD complications (C2 vs. C3, ED: 1.94 [1.70-2.21]; hospitalizations: 1.61 [1.45-1.78]), but not in outpatient visits. Although the most commonly reported SCD complication among all patients was pain, patients who received ICT were less likely to experience pain and other complications than those who did not. These results highlight the need for increased patient and provider education on the importance of comprehensive disease management.

  11. Correlation of transcranial Doppler ultrasonography with MRI and MRA in the evaluation of sickle cell disease patients with prior stroke

    International Nuclear Information System (INIS)

    Kogutt, M.S.; Goldwag, S.S.; Gupta, K.L.; Kaneko, K.; Humbert, J.R.

    1994-01-01

    We prospectively evaluated a group of patients with sickle cell disease and a clinical history of prior stroke, comparing transcranial Doppler sonography (TCD) to both magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) to determine its efficacy for the detection of flow abnormalities associated with prior cerebral infarction. Using MRI as the standard examination, there was 94 % sensitivity and 30 % specificity, and using MRA as the standard examination, there was 91 % sensitivity and 22 % specificity. We concur with other reports that the transcranial Doppler examination is a highly sensitive study. In our group of sickle cell disease patients with prior stroke, TCD reliably detected flow abnormalities that correlated to areas of prior cerebral infarction. (orig.)

  12. Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease

    International Nuclear Information System (INIS)

    Fink, J.K.; Correll, P.H.; Perry, L.K.; Brady, R.O.; Karlsson, S.

    1990-01-01

    Retroviral gene transfer has been used successfully to correct the glucocerebrosidase (GCase) deficiency in primary hematopoietic cells from patients with Gaucher disease. For this model of somatic gene therapy, the authors developed a high-titer, amphotropic retroviral vector designated NTG in which the human GCase gene was driven by the mutant polyoma virus enhancer/herpesvirus thymidine kinase gene (tk) promoter (Py + /Htk). NTG normalized GCase activity in transduced Gaucher fibroblasts and efficiently infected human monocytic and erythroleukemic cell lines. RNA blot-hybridization (Northern blot) analysis of these hemaptopoietic cell lines showed unexpectedly high-level expression from the Moloney murine leukemia virus long terminal repeat (Mo-MLV LTR) and levels of Py + /Htk enhancer/promoter-initiated human GCase RNA that approximated endogenous GCase RNA levels. Furthermore, NTG efficiently infected human hematopoietic progenitor cells. Detection of the provirus in approximately one-third of NTG-infected progenitor colonies that had not been selected in G418-containing medium indicates that relative resistance to G418 underestimated the actual gene transfer efficiency. Northern blot analysis of NTG-infected, progenitor-derived cells showed expression from both the Mo-MLV LTR and the Py + /Htk enhancer/promoter. NTG-transduced hematopoietic progenitor cells from patients with Gaucher disease generated progeny in which GCase activity has been normalized

  13. Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease

    Energy Technology Data Exchange (ETDEWEB)

    Fink, J.K.; Correll, P.H.; Perry, L.K.; Brady, R.O.; Karlsson, S. (National Institutes of Health, Bethesda, MD (USA))

    1990-03-01

    Retroviral gene transfer has been used successfully to correct the glucocerebrosidase (GCase) deficiency in primary hematopoietic cells from patients with Gaucher disease. For this model of somatic gene therapy, the authors developed a high-titer, amphotropic retroviral vector designated NTG in which the human GCase gene was driven by the mutant polyoma virus enhancer/herpesvirus thymidine kinase gene (tk) promoter (Py{sup +}/Htk). NTG normalized GCase activity in transduced Gaucher fibroblasts and efficiently infected human monocytic and erythroleukemic cell lines. RNA blot-hybridization (Northern blot) analysis of these hemaptopoietic cell lines showed unexpectedly high-level expression from the Moloney murine leukemia virus long terminal repeat (Mo-MLV LTR) and levels of Py{sup +}/Htk enhancer/promoter-initiated human GCase RNA that approximated endogenous GCase RNA levels. Furthermore, NTG efficiently infected human hematopoietic progenitor cells. Detection of the provirus in approximately one-third of NTG-infected progenitor colonies that had not been selected in G418-containing medium indicates that relative resistance to G418 underestimated the actual gene transfer efficiency. Northern blot analysis of NTG-infected, progenitor-derived cells showed expression from both the Mo-MLV LTR and the Py{sup +}/Htk enhancer/promoter. NTG-transduced hematopoietic progenitor cells from patients with Gaucher disease generated progeny in which GCase activity has been normalized.

  14. Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I-associated neuroimmunological disease.

    Science.gov (United States)

    Yamano, Yoshihisa; Takenouchi, Norihiro; Li, Hong-Chuan; Tomaru, Utano; Yao, Karen; Grant, Christian W; Maric, Dragan A; Jacobson, Steven

    2005-05-01

    CD4(+)CD25(+) Tregs are important in the maintenance of immunological self tolerance and in the prevention of autoimmune diseases. As the CD4(+)CD25(+) T cell population in patients with human T cell lymphotropic virus type I-associated (HTLV-I-associated) myelopathy/tropical spastic paraparesis (HAM/TSP) has been shown to be a major reservoir for this virus, it was of interest to determine whether the frequency and function of CD4(+)CD25(+) Tregs in HAM/TSP patients might be affected. In these cells, both mRNA and protein expression of the forkhead transcription factor Foxp3, a specific marker of Tregs, were lower than those in CD4(+)CD25(+) T cells from healthy individuals. The virus-encoded transactivating HTLV-I tax gene was demonstrated to have a direct inhibitory effect on Foxp3 expression and function of CD4(+)CD25(+) T cells. This is the first report to our knowledge demonstrating the role of a specific viral gene product (HTLV-I Tax) on the expression of genes associated with Tregs (in particular, foxp3) resulting in inhibition of Treg function. These results suggest that direct human retroviral infection of CD4(+)CD25(+) T cells may be associated with the pathogenesis of HTLV-I-associated neurologic disease.

  15. Role of T. cruzi exposure in the pattern of T cell cytokines among chronically infected HIV and Chagas disease patients

    Directory of Open Access Journals (Sweden)

    Tania Regina Tozetto-Mendoza

    Full Text Available OBJECTIVES: The impact of Chagas disease (CD in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10, those with Chagas disease and HIV infection (CO, n=11, those with only HIV (HIV, n=14 and healthy individuals (C, n=15. RESULTS: We found 1 a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2 a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3 a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4 a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease.

  16. Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis.

    Science.gov (United States)

    Asik, Mehmet; Binnetoglu, Emine; Sen, Hacer; Gunes, Fahri; Muratli, Asli; Kankaya, Duygu; Uysal, Fatma; Sahin, Mustafa; Ukinc, Kubilay

    2015-01-01

    Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). We reviewed reports of primary SCC of the thyroid gland published in the English literature. We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases.

  17. Red blood cell alloimmunization in patients with sickle cell disease in Turkey: a single center retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Soner Solmaz

    2016-12-01

    Results: Of 216 SCD patients included in the study. Alloimmunization was detected in 67 (31.0% out of 216 patients who underwent transfusion, and in 17 (30.4% out of 56 patients in Group 1 and in 50 (31.3% out of 160 patients in Group 2. When the patients were analyzed according to alloimmunization development, our study revealed that neither SCD complications are a risk factor for alloimmunization nor alloimmunization increases mortality rates. Conclusion: High alloimmunization frequency found in our study suggests the insufficient adherence of alloimmunization-prevention policies in RBC transfusions performed except experienced institutions. Therefore alloimmunization may be reduced or prevented through performing extended red cell typing among SCD patients. [Cukurova Med J 2016; 41(4.000: 622-627

  18. Changes seen on computed tomography of the chest in mildly symptomatic adult patients with sickle cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Ursula David; Lopes, Agnaldo Jose; Maioli, Maria Christina Paixao; Soares, Andrea Ribeiro; Melo, Pedro Lopes de; Mogami, Roberto, E-mail: agnaldolopes.uerj@gmail.com [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil)

    2016-07-15

    Objective: To describe and quantify the main changes seen on computed tomography of the chest in mildly symptomatic adult patients with sickle cell disease, as well as to evaluate the radiologist accuracy in determining the type of haemoglobinopathy. Materials and Methods: A prospective study involving 44 adult patients with sickle cell disease who underwent inspiration and expiration computed tomography of the chest. The frequency of tomography findings and the extent of involvement are reported. We also calculated radiologist accuracy in determining the type of haemoglobinopathy by analyzing the pulmonary alterations and morphology of the spleen. Results: The changes found on computed tomography scans, in descending order of frequency, were as follows: fibrotic opacities (81.8%); mosaic attenuation (56.8%); architectural distortion (31.8%); cardiomegaly (25.0%); lobar volume reduction (18.2%); and increased caliber of peripheral pulmonary arteries (9.1%). For most of the findings, the involvement was considered mild, five or fewer lung segments being affected. The accuracy in determining the type of haemoglobinopathy (HbSS group versus not HbSS group) was 72.7%. Conclusion: In adult patients with sickle cell disease, the main tomography findings reflect fibrotic changes. In addition, computed tomography can be helpful in differentiating among haemoglobinopathies. (author)

  19. Changes seen on computed tomography of the chest in mildly symptomatic adult patients with sickle cell disease

    International Nuclear Information System (INIS)

    Alves, Ursula David; Lopes, Agnaldo Jose; Maioli, Maria Christina Paixao; Soares, Andrea Ribeiro; Melo, Pedro Lopes de; Mogami, Roberto

    2016-01-01

    Objective: To describe and quantify the main changes seen on computed tomography of the chest in mildly symptomatic adult patients with sickle cell disease, as well as to evaluate the radiologist accuracy in determining the type of haemoglobinopathy. Materials and Methods: A prospective study involving 44 adult patients with sickle cell disease who underwent inspiration and expiration computed tomography of the chest. The frequency of tomography findings and the extent of involvement are reported. We also calculated radiologist accuracy in determining the type of haemoglobinopathy by analyzing the pulmonary alterations and morphology of the spleen. Results: The changes found on computed tomography scans, in descending order of frequency, were as follows: fibrotic opacities (81.8%); mosaic attenuation (56.8%); architectural distortion (31.8%); cardiomegaly (25.0%); lobar volume reduction (18.2%); and increased caliber of peripheral pulmonary arteries (9.1%). For most of the findings, the involvement was considered mild, five or fewer lung segments being affected. The accuracy in determining the type of haemoglobinopathy (HbSS group versus not HbSS group) was 72.7%. Conclusion: In adult patients with sickle cell disease, the main tomography findings reflect fibrotic changes. In addition, computed tomography can be helpful in differentiating among haemoglobinopathies. (author)

  20. Disseminated Tumor Cells in Prostate Cancer Patients after Radical Prostatectomy and without Evidence of Disease Predicts Biochemical Recurrence

    Science.gov (United States)

    Morgan, Todd M.; Lange, Paul H.; Porter, Michael P.; Lin, Daniel W.; Ellis, William J.; Gallaher, Ian S.; Vessella, Robert L.

    2011-01-01

    Purpose Men with apparently localized prostate cancer often relapse years after radical prostatectomy (RP). We sought to determine if epithelial-like cells identified from bone marrow (BM) in patients after RP (commonly called disseminated tumor cells, DTC) were associated with biochemical recurrence (BR). Experimental Design We obtained BM aspirates from 569 men prior to RP and from 34 healthy men with PSA<2.5 ng/ml to establish a comparison group. Additionally, an analytic cohort consisting of 98 patients after RP with no evidence of disease (NED) was established to evaluate the relationship between DTC and BR. Epithelial cells in the BM were detected by magnetic bead enrichment with antibodies to CD45 and CD61 (negative selection) followed by antibodies to human epithelial antigen (positive selection) and confirmation with FITC-labeled anti-BerEP4 antibody. Results DTC were present in 72% (408/569) of patients prior to RP. There was no correlation with pathologic stage, Gleason grade, or pre-operative PSA. Three of 34 controls (8.8%) had DTC present. In patients NED post-RP, DTC were present in 56/98 (57%). DTC were detected in 12/14 (86%) NED patients post-RP who subsequently suffered BR. Presence of DTC in NED patients was an independent predictor of recurrence (HR 6.9, CI 1.03–45.9). Conclusions Approximately 70% of men undergoing RP had DTC detected in their BM prior to surgery, suggesting that these cells escape early in the disease. Though pre-operative DTC status does not correlate with pathologic risk factors, persistence of DTC after RP in NED patients was an independent predictor of recurrence. PMID:19147774

  1. Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF.

    Science.gov (United States)

    Rotondo, John Charles; Bononi, Ilaria; Puozzo, Andrea; Govoni, Marcello; Foschi, Valentina; Lanza, Giovanni; Gafà, Roberta; Gaboriaud, Pauline; Touzé, Françoise Antoine; Selvatici, Rita; Martini, Fernanda; Tognon, Mauro

    2017-07-15

    Purpose: The purpose of this investigation was to characterize Merkel cell carcinomas (MCC) arisen in patients affected by autoimmune diseases and treated with biologic drugs. Experimental Design: Serum samples from patients with MCC were analyzed for the presence and titer of antibodies against antigens of the oncogenic Merkel cell polyomavirus (MCPyV). IgG antibodies against the viral oncoproteins large T (LT) and small T (ST) antigens and the viral capsid protein-1 were analyzed by indirect ELISA. Viral antigens were recombinant LT/ST and virus-like particles (VLP), respectively. MCPyV DNA sequences were studied using PCR methods in MCC tissues and in peripheral blood mononuclear cells (PBMC). Immunohistochemical (IHC) analyses were carried out in MCC tissues to reveal MCPyV LT oncoprotein. Results: MCPyV DNA sequences identified in MCC tissues showed 100% homology with the European MKL-1 strain. PBMCs from patients tested MCPyV-negative. Viral DNA loads in the three MCC tissues were in the 0.1 to 30 copy/cell range. IgG antibodies against LT/ST were detected in patients 1 and 3, whereas patient 2 did not react to the MCPyV LT/ST antigen. Sera from the three patients with MCC contained IgG antibodies against MCPyV VP1. MCC tissues tested MCPyV LT-antigen-positive in IHC assays, with strong LT expression with diffuse nuclear localization. Normal tissues tested MCPyV LT-negative when employed as control. Conclusions: We investigated three new MCCs in patients affected by rheumatologic diseases treated with biologic drugs, including TNF. A possible cause-effect relationship between pharmacologic immunosuppressive treatment and MCC onset is suggested. Indeed, MCC is associated with MCPyV LT oncoprotein activity. Clin Cancer Res; 23(14); 3929-34. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. Anti-HI can cause a severe delayed hemolytic transfusion reaction with hyperhemolysis in sickle cell disease patients.

    Science.gov (United States)

    Ibanez, Clara; Habibi, Anoosha; Mekontso-Dessap, Armand; Chadebech, Philippe; Chami, Btissam; Bierling, Philippe; Galactéros, Frédéric; Rieux, Claire; Nataf, Joëlle; Bartolucci, Pablo; Peyrard, Thierry; Pirenne, France

    2016-07-01

    Delayed hemolytic transfusion reaction (DHTR) is a life-threatening condition in sickle cell disease (SCD) patients that is frequently complicated by hyperhemolysis. Antibodies resulting from antigen disparity between donors of European ancestry and patients of African ancestry are common, but situations involving antibodies not classically of clinical significance are also encountered. Anti-HI is generally considered to be an innocuous naturally occurring antibody. We describe two cases of hyperhemolysis with anti-HI and provide details of the reported cases. Both SCD patients were polyimmunized and belonged to blood group B. They developed anti-HI that was reactive at 37°C, after the transfusion of group O red blood cell units matched for all known and produced antibodies classically considered to be clinically significant. Both patients developed DHTR with hyperhemolysis. In the first case, a pregnant woman, a second transfusion was unavoidable and the patient died from cardiac arrest. The state of the second patient improved without the need for further transfusion. Three other cases of DHTR with anti-HI have been described in the literature in SCD patients. The two additional cases reported here definitively demonstrate that anti-HI is dangerous in SCD patients. As a result, ABO-identical matching (including A1 status) must be considered in SCD patients with anti-HI. © 2016 AABB.

  3. Hospitalist management of vaso-occlusive pain crisis in patients with sickle cell disease using a pathway of care.

    Science.gov (United States)

    Allen Liles, Edmund; Kirsch, Jonathan; Gilchrist, Michael; Adem, Mukhtar

    2014-04-01

    Patients with sickle cell disease (SCD) suffer from intermittent vaso-occlusive pain crises (VOCs). These crises lead to frequent hospitalizations, significant morbidity, and increased mortality risk. Care pathways can enhance efficiency and quality of care. Our study sought to evaluate the development and implementation of a care pathway for patients with SCD experiencing VOCs. The University of North Carolina (UNC) Comprehensive Sickle Cell Program provides all levels of care for a large population of patients with sickle cell anemia. All patients admitted to UNC Hospitals with SCD VOCs from January 2009 through June 2011 were evaluated. During this time period, we also assessed sequential prospective cohorts during progressive phases of developing and implementing a quality improvement and pathway of care program for this patient population in our study. The developed pathway entailed geographic localization for VOC patients, a single group of faculty physicians caring for these patients, and early use of patient-controlled analgesia (PCA) to achieve pain control. Physicians from the UNC Hospital Medicine Program were responsible for the initiatives. Cohorts were compared to a baseline historical control. Outcomes of interest included patient length of stay (LOS) in the hospital, 30-day readmission rate, need for transfusion, incidence of acute chest syndrome, use of naloxone, and use of PCA. Compared with an historical baseline cohort, the development and implementation of a VOC care pathway for patients with SCD led to reduction in average hospital LOS by 1.44 days (P management of patients with SCD VOCs using a care pathway that emphasizes early, aggressive PCA-based pain control is associated with reduced hospital LOS. The LOS reduction seen in our study is clinically meaningful. Notably, other measures of patient outcomes and quality of care metrics did not change significantly, and some trended towards improvement.

  4. Multiple bone and joint disease in a sickle cell anaemia patient: a case report

    Directory of Open Access Journals (Sweden)

    John Ayodele Olaniyi

    2012-05-01

    Multidisciplinary approach was applied to her management and she was finally discharged home on a wheelchair. This case reflects not only the high susceptibility of SCD patients to infection, but also the morbidity and the attendant complications. It also highlights the need to forestall vaso-occlusive crisis (VOC which often predisposes them to developing osteomyelitis. There is a need to have a highly organized, well-equipped and highly subsidized Sickle Cell and rehabilitation Center in order to further improve the care of SCD patients.

  5. Generation of an integration-free induced pluripotent stem cell line (CSC-43 from a patient with sporadic Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ana Marote

    2018-03-01

    Full Text Available An induced pluripotent stem cell (iPSC line was generated from a 36-year-old patient with sporadic Parkinson's disease (PD. Skin fibroblasts were reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43 exhibits expression of common pluripotency markers, in vitro differentiation into three germ layers and normal karyotype. This iPSC line can be used to study the mechanisms underlying the development of PD.

  6. Generation of a human induced pluripotent stem cell line (CSC-42 from a patient with sporadic form of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ekaterina Savchenko

    2018-03-01

    Full Text Available Skin fibroblasts were collected from a 44-year-old patient with sporadic case of Parkinson's disease (PD. The non-integrating Sendai virus vector encoding OCT3/4, SOX2, c-MYC and KLF4 was used to reprogram fibroblasts into induced pluripotent stem cells (iPSCs. Generated iPSCs had normal karyotypes, expressed common stem cell markers, and were capable of differentiating into all three germ layers. Generated line could be used for PD modeling to understand the mechanisms that influence the disorder.

  7. Differential expression of NK receptors CD94 and NKG2A by T cells in rheumatoid arthritis patients in remission compared to active disease.

    LENUS (Irish Health Repository)

    Walsh, Ceara E

    2011-01-01

    TNF inhibitors (TNFi) have revolutionised the treatment of rheumatoid arthritis (RA). Natural killer (NK) cells and Natural Killer Cell Receptor+ T (NKT) cells comprise important effector lymphocytes whose activity is tightly regulated through surface NK receptors (NKRs). Dysregulation of NKRs in patients with autoimmune diseases has been shown, however little is known regarding NKRs expression in patients with TNFi-induced remission and in those who maintain remission vs disease flare following TNFi withdrawal.

  8. Extent of silent cerebral infarcts in adult sickle-cell disease patients on magnetic resonance imaging: is there a correlation with the clinical severity of disease?

    Directory of Open Access Journals (Sweden)

    Ekaterini Solomou

    2013-02-01

    Full Text Available The aim of this paper is to correlate the extent of silent cerebral infarcts (SCIs on magnetic resonance imaging (MRI with the clinical severity of sickle cell disease (SCD in adult patients. Twenty-four consecutive adult asymptomatic SCD patients (11 male and 13 female with a mean age of 38.4 years (range 20-59 were submitted to brain MRI on a 1 Tesla Gyroscan Intera, Philips MR scanner with a dedicated head coil. The protocol consisted of TSE T2-weighted and FLAIR images on the axial and coronal planes. MRI readings were undertaken by two radiologists and consensus readings. Patients were compound heterozygotes (HbS/β-thal. The extent of SCIs was classified from 0-2 with 0 designating no lesions. Clinical severity was graded as 0-2 by the hematologist, according to the frequency and severity of vaso-occlusive crises. There was no statistically significant correlation between the severity of clinical disease and the extent of SCIs on MR imaging. The extent of SCI lesions did not differ statistically between younger and older patients. Patients receiving hydroxyurea had no statistically significant difference in the extent of SCI lesions. The extent of SCIs in heterozygous (HbS/β-thal SCD patients is not age related and may be quite severe even in younger (<38.4 years patients. However the extent of SCIs is not correlated with the severity of clinical disease.

  9. The Fc Receptor Polymorphisms and Expression of Neutrophil Activation Markers in Patients with Sickle Cell Disease from Western India

    Directory of Open Access Journals (Sweden)

    Harshada K. Kangne

    2013-01-01

    Full Text Available Objective. Sickle cell disease has variable clinical manifestations. Activation of neutrophils plays an important role in the initiation and propagation of vaso occlusive crises which can be analysed by determining the expression of neutrophil antigens such as CD16, CD32, and CD62L. The common FcγR polymorphisms (FcγRIIA and FcγRIIIB are considered to influence clinical presentation. This study focuses on distribution of FcγR polymorphisms and their association with neutrophil activity among the patients from western India. Methods. In this paper 127 sickle cell anemia patients and 58 patients with sickle-β-thalassemia (median age 12±8.58 years with variable clinical phenotypes along with 175 normals were investigated. FcγRs polymorphisms were analysed by RFLP and AS-PCR. Activation of neutrophils was measured by flow cytometry. Results. The genotypic frequency of the H/R genotype of FcγRIIA and the NA1/NA1 genotype of FcγRIIIB was significantly decreased in patients compared to normals (P-0.0074, P-0.0471, resp.. We found a significant difference in the expression of CD32 and CD62L among the patients as against normals. A significantly higher expression of CD32 was seen in the milder patients with the H/H genotype (P-0.0231, whereas the expression of CD16 was higher in severe patients with the NA2/NA2 genotype (P-0.0312. Conclusion. The two FcγR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils.

  10. Scintigraphic follow-up of the effects of therapy with hydroxyurea on splenic function in patients with sickle cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Allan [Division of Nuclear Medicine, Department of Radiology, Campinas State University (UNICAMP), Campinas (Brazil); Servico de Medicina Nuclear, Hospital das Clinicas da UNICAMP, Campina (Brazil); Pinheiro, Vitoria; Anjos, Ana Claudia; Brandalise, Silvia [Centro Infantil Domingos A. Boldrini, Campinas (Brazil); Fahel, Fernanda; Lima, Mariana; Etchebehere, Elba; Ramos, Celso; Camargo, Edwaldo E. [Division of Nuclear Medicine, Department of Radiology, Campinas State University (UNICAMP), Campinas (Brazil)

    2002-04-01

    Patients with sickle cell disease (SCD) may develop functional asplenia as a chronic complication, secondary to repeated episodes of polymerisation of haemoglobin S. It is known that increased plasma concentrations of fetal haemoglobin (HbF) reduce the polymerisation of haemoglobin S. Hydroxyurea is a chemotherapeutic agent capable of increasing HbF levels in the red blood cells and its use has recently been proposed in the treatment of SCD. The objective of this study was to evaluate the effects of long-term therapy with hydroxyurea on recovery of splenic function. Twenty-one patients (aged 3-22 years; 14 with SS haemoglobinopathy, 7 with S{beta}{sup 0} haemoglobinopathy) were studied with liver/spleen scintigraphy before and after 6 and 12 months of treatment. All studies were submitted to visual inspection and semi-quantitative analyses using spleen/liver ratios. Imaging prior to treatment demonstrated functional asplenia in nine SS patients and one S{beta}{sup 0} patient and impaired splenic function in five SS patients and six S{beta}{sup 0} patients. After treatment, splenic function improved in ten patients, remained unchanged in eight and worsened in three. Using liver/spleen imaging, it was possible to demonstrate that hydroxyurea is capable of improving splenic function in some SCD patients. Improvement is not always possible and frequently does not lead to a normal splenic function even after 1 year of treatment. (orig.)

  11. Scintigraphic follow-up of the effects of therapy with hydroxyurea on splenic function in patients with sickle cell disease

    International Nuclear Information System (INIS)

    Santos, Allan; Pinheiro, Vitoria; Anjos, Ana Claudia; Brandalise, Silvia; Fahel, Fernanda; Lima, Mariana; Etchebehere, Elba; Ramos, Celso; Camargo, Edwaldo E.

    2002-01-01

    Patients with sickle cell disease (SCD) may develop functional asplenia as a chronic complication, secondary to repeated episodes of polymerisation of haemoglobin S. It is known that increased plasma concentrations of fetal haemoglobin (HbF) reduce the polymerisation of haemoglobin S. Hydroxyurea is a chemotherapeutic agent capable of increasing HbF levels in the red blood cells and its use has recently been proposed in the treatment of SCD. The objective of this study was to evaluate the effects of long-term therapy with hydroxyurea on recovery of splenic function. Twenty-one patients (aged 3-22 years; 14 with SS haemoglobinopathy, 7 with Sβ 0 haemoglobinopathy) were studied with liver/spleen scintigraphy before and after 6 and 12 months of treatment. All studies were submitted to visual inspection and semi-quantitative analyses using spleen/liver ratios. Imaging prior to treatment demonstrated functional asplenia in nine SS patients and one Sβ 0 patient and impaired splenic function in five SS patients and six Sβ 0 patients. After treatment, splenic function improved in ten patients, remained unchanged in eight and worsened in three. Using liver/spleen imaging, it was possible to demonstrate that hydroxyurea is capable of improving splenic function in some SCD patients. Improvement is not always possible and frequently does not lead to a normal splenic function even after 1 year of treatment. (orig.)

  12. Traumatic Exposure History as a Risk Factor for Chronic Pain in Adult Patients with Sickle Cell Disease.

    Science.gov (United States)

    Works, Teresa; Jones, Sasia; Grady, James; Andemariam, Biree

    2016-02-01

    This article describes the impact of the integration of a licensed clinical social worker (LCSW) with expertise in behavioral health on identification of risk factors for chronic pain in a cohort of adults with sickle cell disease. Authors conducted a retrospective chart review of all visits to the adult sickle cell center during the first six months of LCSW integration. Demographics, clinical history, and LCSW notes were reviewed. Overall, 71 patients were introduced to the LCSW; 55 percent of them had chronic pain. Patients with chronic pain were older, used opioids daily, took hydroxyurea, reported higher daily pain scores, and underwent more acute care visits and hospitalizations for pain with longer stays. Fifty-eight (81 percent) patients requested concrete social work services such as transportation and housing. Thirty-two patients (55 percent) expressed a desire for mental health counseling while receiving concrete services. Twenty-two (69 percent) of these patients self-disclosed at least one traumatic experience. In fact, a statistically significant relationship between chronic pain and a history of trauma was identified (p = 0.001). Results suggest that sickle cell patients should receive clinical social work services to assess for traumatic exposures that may influence chronic pain.

  13. Interventions for patients and caregivers to improve knowledge of sickle cell disease and recognition of its related complications.

    Science.gov (United States)

    Asnani, Monika R; Quimby, Kim R; Bennett, Nadia R; Francis, Damian K

    2016-10-06

    Sickle cell disease is a group of genetic diseases which is especially prevalent in tropical and subtropical regions; however, forced migration and ongoing population movement have spread it throughout the world, with estimated birth rates reaching 0.49 per 1000 in the Americas, 0.07 per 1000 in Europe, 0.68 per 1000 in South and Southeast Asia, and 10.68 per 1000 in Africa. Life for individuals with sickle cell disease can be affected by repeated acute complications and compounded by progressive organ damage. Studies reveal that when people with chronic illness learn self-management, their clinical outcomes and quality of life improves; and they show lower dependence on healthcare services. There are, however, no reviews identifying which interventions improve knowledge and little is known about the impact of patient or care-giver knowledge on clinical and psychosocial outcomes in people with sickle cell disease. 1. To determine the effectiveness of patient- and caregiver-centred educational interventions for changing knowledge and understanding of sickle cell disease among patients as well as caregivers of people with the disease.2. To assess the effectiveness and safety of patient- and caregiver-centred educational interventions and programs for the recognition of signs and symptoms of disease-related morbidity, adherence to treatment and healthcare utilization in patients with sickle cell disease. The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Additional trials were sought from the reference lists of the trials and reviews identified by the search strategy.Date of last search: 11 April 2016. Randomized and quasi-randomized controlled trials which evaluate the effectiveness of individual- and group-based interventions for either the patient with sickle cell disease or their caregivers, or both

  14. Personalized biomarkers to monitor disease progression in advanced non-small-cell lung cancer patients treated with icotinib.

    Science.gov (United States)

    Song, Gaoguang; Liu, Yujie; Wang, Yanying; Ren, Guanjun; Guo, Shuai; Ren, Junling; Zhang, Li; Li, Zhili

    2015-02-02

    Disease-specific humoral immune response-related protein complexes in blood are associated with disease progression. Thirty-one patients with stage IIIB and IV non-small-cell lung cancer (NSCLC) were administered with oral dose of icotinib hydrochloride (150 mg twice daily or 125 mg 3 times daily) for a 28-continuous-day cycle until diseases progressed or unacceptable toxicity occurred. The levels of immunoinflammation-related protein complexes (IIRPCs) in a series of plasma samples from 31 NSCLC patients treated with icotinib hydrochloride were determined by an optimized native polyacrylamide gel electrophoresis. Three characteristic patterns of the IIRPCs, named as patterns a, b, and c, respectively, were detected in plasma samples from 31 patients. Prior to the treatment, there were 18 patients in pattern a consisting of 5 IIRPCs, 9 in pattern b consisting of six IIRPCs, and 4 in pattern c without the IIRPCs. The levels of the IIRPCs in 27 patients were quantified. Our results indicate that the time length of humoral immune and inflammation response (TLHIIR) was closely associated with disease progression, and the median TLHIIR was 22.0 weeks, 95% confidence interval: 16.2 to 33.0 weeks, with a lead time of median 11 weeks relative to clinical imaging evidence confirmed by computed tomography or magnetic resonance imaging (the median progression-free survival, 34.0 weeks, 95% confidence interval: 27.9 to 49.0 weeks). The complex relationships between humoral immune response, acquired resistance, and disease progression existed. Personalized IIRPCs could be indicators to monitor the disease progression. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Morbiletalidad en pacientes adultos con drepanocitosis Morbimortality rates in adult patients with sickle cell disease

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    Sergio Machín García

    2004-08-01

    Full Text Available Se estudiaron 397 pacientes adultos con drepanocitosis, seguidos entre enero de 1973 y diciembre de 1997; 200 del sexo femenino y 197 del masculino. De estos, 305 con anemia drepanocítica, 63 con hemoglobinopatía SC y 29 con Sb talasemia. La mediana de seguimiento fue de 14,3 años. La media anual de ingresos y transfusiones fue menor en la hemoglobinopatía SC (pA study was performed on 397 adult patients with sickle cell anemia, who had been followed up from January 1973 to December 1997. Two hundred were females and 197 males; 305 of these patients presented with sickle cell anemia, 63 with SC hemoglobinopathy and 29 with Sb thalassemia. The mean follow-up period was 14,3 years. The yearly admission and blood transfusion mean was lower in SC hemoglobinopathy(p<0,001. Painful vasoocclusive crisis was more frequent in Sb thalassemia whereas infections often occurred in sickle cell anemia (p<0,001. One hundred four pregnancies were developed from 87 females. There were 4 maternal deaths and 10 perinatal deaths. Differences were found in hemoglobin and reticulocyte values among hemoglobinopathies (p<0,001 but no difference was seen between sexes or among age groups (18-29 y, 30-40 y and over 40 y. Fetal hemoglobin values did not show significant difference between sexes, although they were higher in sickle cell anemia. Global survival estimates were 53 years in sickle cell anemia, 59 years in SC hemoglobinopathy and 48 in Sb thalassemia (p< 0,05. The most frequent cases of death were hepatic complications, encephalic vascular attacks and infections

  16. Comprehensive evaluation of nutritional status before and after hematopoietic stem cell transplantation in 170 patients with hematological diseases.

    Science.gov (United States)

    Liu, Peng; Wang, Boshi; Yan, Xia; Cai, Jingjing; Wang, Yu

    2016-12-01

    To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation (HSCT), and explore optimal methods for assessing nutritional status in patients with hematological diseases. This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People's Hospital between May 2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002 (NRS-2002), Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA) and Malnutrition Universal Screening Tools (MUST), in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms. After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with 100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk, compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT, compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT. Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment

  17. ANTI-B-CELL THERAPY AT IMMUNE INFLAMMATORY RHEUMATIC DISEASES: EFFICACY AND TOLERABILITY IN 229 PATIENTS

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    L. P. Ananieva

    2014-01-01

    Full Text Available Objective: to assess the efficacy and tolerability of Rituximab treatment in patients with serious immune inflammatory rheumatic diseases (IRD like systemic lupus erythematosus (SLE, systemic sclerosis (SS, systemic vasculitis (SV, Sjogren syndrome (SjS, dermatomyositis/polymyositis (DM/PM.Subjects and methods. The clinical efficacy has been analyzed in 229 patients with IRD: SLE (n=97, SV (n=50, SS (n=40, SjS (n=23 and DM/PM (n=19. Rituximab treatment was accompanied by administration of glucocorticoids and/or immunosuppressive drugs. Most patients demonstrated resistance to or low tolerability of standard therapy. Efficacy of treatment was analyzed in each group with the criteria relevant for each disease. To compare clinical response to the treatment between the groups we used gradations accepted by international registries: complete (good response, partial response, no response. Average duration of monitoring comprised 72 (1–288 weeks after the first introduction of Rituximab. Average Rituximab dose administered to patients over the period of monitoring was low and varied from 1.6±0.84 in DM/PM to 3.1±1.75 in SV. About 80% of patients received one or two courses of Rituximab except for patients with SS (half of them received three and more courses.Results. «Complete response» was observed in 50.6%, «partial response» – in 35% of patients. Rituximab courses provided positive dynamics in clinical scores and allowed to reduce supportive dose of glucocorticoids and to lower the dose or withdraw of immune-stimulating drugs. Multiple Rituximab courses provided stable and longlasting effect. Recurrences were observed less frequently, whereas efficacy of the therapy increased during a year and longer. Occurrence of adverse events and mortality rate were comparable to data of other national Rituximab registries.Conclusion. The results of the study may prove administration of Rituximab in patients with resistance to standard

  18. Gene correction of HAX1 reversed Kostmann disease phenotype in patient-specific induced pluripotent stem cells.

    Science.gov (United States)

    Pittermann, Erik; Lachmann, Nico; MacLean, Glenn; Emmrich, Stephan; Ackermann, Mania; Göhring, Gudrun; Schlegelberger, Brigitte; Welte, Karl; Schambach, Axel; Heckl, Dirk; Orkin, Stuart H; Cantz, Tobias; Klusmann, Jan-Henning

    2017-06-13

    Severe congenital neutropenia (SCN, Kostmann disease) is a heritable disorder characterized by a granulocytic maturation arrest. Biallelic mutations in HCLS1 associated protein X-1 ( HAX1 ) are frequently detected in affected individuals, including those of the original pedigree described by Kostmann in 1956. To date, no faithful animal model has been established to study SCN mediated by HAX1 deficiency. Here we demonstrate defective neutrophilic differentiation and compensatory monocyte overproduction from patient-derived induced pluripotent stem cells (iPSCs) carrying the homozygous HAX1 W44X nonsense mutation. Targeted correction of the HAX1 mutation using the CRISPR-Cas9 system and homologous recombination rescued neutrophil differentiation and reestablished an HAX1 and HCLS1 -centered transcription network in immature myeloid progenitors, which is involved in the regulation of apoptosis, apoptotic mitochondrial changes, and myeloid differentiation. These findings made in isogenic iPSC-derived myeloid cells highlight the complex transcriptional changes underlying Kostmann disease. Thus, we show that patient-derived HAX1 W44X -iPSCs recapitulate the Kostmann disease phenotype in vitro and confirm HAX1 mutations as the disease-causing monogenic lesion. Finally, our study paves the way for nonvirus-based gene therapy approaches in SCN.

  19. Characterization of functional brain activity and connectivity using EEG and fMRI in patients with sickle cell disease.

    Science.gov (United States)

    Case, Michelle; Zhang, Huishi; Mundahl, John; Datta, Yvonne; Nelson, Stephen; Gupta, Kalpna; He, Bin

    2017-01-01

    Sickle cell disease (SCD) is a red blood cell disorder that causes many complications including life-long pain. Treatment of pain remains challenging due to a poor understanding of the mechanisms and limitations to characterize and quantify pain. In the present study, we examined simultaneously recording functional MRI (fMRI) and electroencephalogram (EEG) to better understand neural connectivity as a consequence of chronic pain in SCD patients. We performed independent component analysis and seed-based connectivity on fMRI data. Spontaneous power and microstate analysis was performed on EEG-fMRI data. ICA analysis showed that patients lacked activity in the default mode network (DMN) and executive control network compared to controls. EEG-fMRI data revealed that the insula cortex's role in salience increases with age in patients. EEG microstate analysis showed patients had increased activity in pain processing regions. The cerebellum in patients showed a stronger connection to the periaqueductal gray matter (involved in pain inhibition), and negative connections to pain processing areas. These results suggest that patients have reduced activity of DMN and increased activity in pain processing regions during rest. The present findings suggest resting state connectivity differences between patients and controls can be used as novel biomarkers of SCD pain.

  20. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease

    International Nuclear Information System (INIS)

    Oe, Shinji; Miyagawa, Koichiro; Honma, Yuichi; Harada, Masaru

    2016-01-01

    Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease.

  1. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease

    Energy Technology Data Exchange (ETDEWEB)

    Oe, Shinji, E-mail: ooes@med.uoeh-u.ac.jp; Miyagawa, Koichiro, E-mail: koichiro@med.uoeh-u.ac.jp; Honma, Yuichi, E-mail: y-homma@med.uoeh-u.ac.jp; Harada, Masaru, E-mail: msrharada@med.uoeh-u.ac.jp

    2016-09-10

    Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease.

  2. Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD

    Directory of Open Access Journals (Sweden)

    Christopher L Edwards

    2007-01-01

    Full Text Available Christopher L Edwards1, Renee Dunn Raynor1, Miriam Feliu1, Camela McDougald1, Stephanie Johnson2, Donald Schmechel3, Mary Wood1, Gary G Bennett4, Patrick Saurona5, Melanie Bonner1, Chante’ Wellington1, Laura M DeCastro6, Elaine Whitworth6, Mary Abrams6, Patrick Logue1, Lekisha Edwards1, Salutario Martinez7, Keith E Whitfield81Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; 2American Psychological Association, Science Directorate, Washington, DC, USA; 3Department of Medicine, Division of Neurology, Duke University Medical Center, Durham, NC, USA; 4Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA, USA; 5Taub Institute For Research on Alzheimer’s Disease and The Aging Brain, Columbia University, New York, NY, USA; 6Department of Medicine, Division of Hematology, Duke University Medical Center, Durham, NC, USA; 7Department of Radiology, Duke University Medical Center, Durham, NC, USA; 8Duke University, Durham, NC, USAAbstract: Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.Keywords: cerebral vascular event, neuropsychological assessment, sickle cell disease, neuroimaging

  3. Adipose-Derived Stromal Cells for Treatment of Patients with Chronic Ischemic Heart Disease (MyStromalCell Trial)

    DEFF Research Database (Denmark)

    Qayyum, Abbas Ali; Mathiasen, Anders Bruun; Mygind, Naja Dam

    2017-01-01

    We aimed to evaluate the effect of intramyocardial injections of autologous VEGF-A165-stimulated adipose-derived stromal cells (ASCs) in patients with refractory angina. MyStromalCell trial is a randomized double-blind placebo-controlled study including sixty patients with CCS/NYHA class II...... to 54) (P= 0.41), and in METs 0.1 (95%CI -1.7 to 1.9) (P= 0.757). The difference between the groups was not significant (P= 0.680,P= 0.608, andP= 0.720 for time duration, watt, and METs, resp.). Intramyocardial delivered VEGF-A165-stimulated ASC treatment was safe but did not improve exercise capacity...

  4. Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases.

    Science.gov (United States)

    Wiley, Luke A; Burnight, Erin R; Songstad, Allison E; Drack, Arlene V; Mullins, Robert F; Stone, Edwin M; Tucker, Budd A

    2015-01-01

    Vision is the sense that we use to navigate the world around us. Thus it is not surprising that blindness is one of people's most feared maladies. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through drug therapy, gene augmentation or a cell-based transplantation approach. In this review we will discuss the use of the induced pluripotent stem cell technology to model and develop various treatment modalities for the treatment of inherited retinal degenerative disease. We will focus on the use of iPSCs for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell transplantation and replacement. Copyright © 2014. Published by Elsevier Ltd.

  5. Stem Cell Transplant Patients and Fungal Infections

    Science.gov (United States)

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  6. Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States.

    Science.gov (United States)

    Delea, Thomas E; Hagiwara, May; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

    2008-04-01

    Deferoxamine mesylate (DFO) reduces morbidity and mortality associated with transfusional iron overload. Data on the utilization and costs of care among U.S. patients receiving DFO in typical clinical practice are limited however. This was a retrospective study using a large U.S. health insurance claims database spanning 1/97-12/04 and representing 40 million members in >70 health plans. Study subjects (n = 145 total, 106 sickle cell disease [SCD], 39 thalassemia) included members with a diagnosis of thalassemia or SCD, one or more transfusions (whole blood or red blood cells), and one or more claims for DFO. Mean transfusion episodes were 12 per year. Estimated mean DFO use was 307 g/year. Central venous access devices were required by 20% of patients. Cardiac disease was observed in 16% of patients. Mean total medical costs were $59,233 per year including $10,899 for DFO and $8,722 for administration of chelation therapy. In multivariate analyses, potential complications of iron overload were associated with significantly higher medical care costs. In typical clinical practice, use of DFO in patients with thalassemia and SCD receiving transfusions is low. Administration costs represent a large proportion of the cost of chelation therapy. Potential complications of iron overload are associated with increased costs. (c) 2007 Wiley-Liss, Inc.

  7. Differences in pain management between hematologists and hospitalists caring for patients with sickle cell disease hospitalized for vasoocclusive crisis.

    Science.gov (United States)

    Shah, Nirmish; Rollins, Margo; Landi, Daniel; Shah, Radhika; Bae, Jonathan; De Castro, Laura M

    2014-03-01

    Sickle cell disease (SCD) is a chronic disease characterized by multiple vaso-occlusive complications and is increasingly cared for by hospitalists. The purpose of this study is to examine differences in pain management between hematologists and hospitalists. We performed a single-institution, retrospective review of pain management patterns and outcomes in adult SCD patients hospitalized for vaso-occlusive crisis. Over 26 months, we found a total of 298 patients (120 cared for by the hematologists and 178 by hospitalists), with a mean age of 32 (range 19-58). Patients cared for by hospitalists had a lower total number of hours on a patient controlled analgesia (PCA) device (171 vs. 212 hours, P=0.11). Hospitalists also were significantly more likely to utilize demand only PCA (42% vs. 23%, P=0.002) and had a significantly lower rate of using both continuous and demand PCA (54% vs. 67%, P=0.04). In addition, patients cared for by hospitalists had a significantly shorter hospitalization (8.4 days) compared to hematologists (10 days, P=0.04) with a non-significant difference in 7 and 30 day readmission rates (7.2% vs. 6.7% and 40% vs. 35% respectively). We found patients cared for by hospitalists more frequently utilized home oral pain medication during admission, had shorter lengths of hospitalization, and did not have a significant increase in readmission rates.

  8. Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Laurent Spahr

    Full Text Available OBJECTIVE: Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD. We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT improved liver function in decompensated ALD. DESIGN: 58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy were randomized early after hospital admission to standard medical therapy (SMT alone (n = 30, including steroids in patients with a Maddrey's score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28. Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC compartment. RESULTS: Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64% from the BMMCT group and 18 patients (53% from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49-5.4 in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001, and proliferating HPC tended to decrease in both groups (-35 and -33%, respectively. CONCLUSION: Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis. TRIAL REGISTRATION

  9. Association of circulating endothelial cells with flow mediated vasodilation and disease activity in patients with systemic lupus erythematosus

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    Rania Gaber

    2014-03-01

    Conclusion: CEC is associated with endothelial dysfunction, disease activity and increased VCAM-1 levels in patients with SLE. These findings suggest a potential role of CEC in the pathophysiology of cardiovascular disease in these patients.

  10. Mitochondrial Alterations in Peripheral Mononuclear Blood Cells from Alzheimer’s Disease and Mild Cognitive Impairment Patients

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    A. Delbarba

    2016-01-01

    Full Text Available It is well recognized that mitochondrial dysfunction contributes to neurodegeneration occurring in Alzheimer’s disease (AD. However, evidences of mitochondrial defects in AD peripheral cells are still inconclusive. Here, some mitochondrial-encoded and nuclear-encoded proteins, involved in maintaining the correct mitochondria machine, were investigated in terms of protein expression and enzymatic activity in peripheral blood mononuclear cells (PBMCs isolated from AD and Mild Cognitive Impairment (MCI patients and healthy subjects. In addition mitochondrial DNA copy number was measured by real time PCR. We found some differences and some similarities between AD and MCI patients when compared with healthy subjects. For example, cytochrome C and cytochrome B were decreased in AD, while MCI showed only a statistical reduction of cytochrome C. On the other hand, both AD and MCI blood cells exhibited highly nitrated MnSOD, index of a prooxidant environment inside the mitochondria. TFAM, a regulator of mitochondrial genome replication and transcription, was decreased in both AD and MCI patients’ blood cells. Moreover also the mitochondrial DNA amount was reduced in PBMCs from both patient groups. In conclusion these data confirmed peripheral mitochondria impairment in AD and demonstrated that TFAM and mtDNA amount reduction could be two features of early events occurring in AD pathogenesis.

  11. Adipose-derived mesenchymal stromal cells from aged patients with coronary artery disease keep mesenchymal stromal cell properties but exhibit characteristics of aging and have impaired angiogenic potential.

    Science.gov (United States)

    Efimenko, Anastasia; Dzhoyashvili, Nina; Kalinina, Natalia; Kochegura, Tatiana; Akchurin, Renat; Tkachuk, Vsevolod; Parfyonova, Yelena

    2014-01-01

    Tissue regeneration is impaired in aged individuals. Adipose-derived mesenchymal stromal cells (ADSCs), a promising source for cell therapy, were shown to secrete various angiogenic factors and improve vascularization of ischemic tissues. We analyzed how patient age affected the angiogenic properties of ADSCs. ADSCs were isolated from subcutaneous fat tissue of patients with coronary artery disease (CAD; n = 64, 43-77 years old) and without CAD (n = 31, 2-82 years old). ADSC phenotype characterized by flow cytometry was CD90(+)/CD73(+)/CD105(+)/CD45(-)/CD31(-) for all samples, and these cells were capable of adipogenic and osteogenic differentiation. ADSCs from aged patients had shorter telomeres (quantitative reverse transcription polymerase chain reaction) and a tendency to attenuated telomerase activity. ADSC-conditioned media (ADSC-CM) stimulated capillary-like tube formation by endothelial cells (EA.hy926), and this effect significantly decreased with the age of patients both with and without CAD. Angiogenic factors (vascular endothelial growth factor, placental growth factor, hepatocyte growth factor, angiopoetin-1, and angiogenin) in ADSC-CM measured by enzyme-linked immunosorbent assay significantly decreased with patient age, whereas levels of antiangiogenic factors thrombospondin-1 and endostatin did not. Expression of angiogenic factors in ADSCs did not change with patient age (real-time polymerase chain reaction); however, gene expression of factors related to extracellular proteolysis (urokinase and its receptor, plasminogen activator inhibitor-1) and urokinase-type plasminogen activator receptor surface expression increased in ADSCs from aged patients with CAD. ADSCs from aged patients both with and without CAD acquire aging characteristics, and their angiogenic potential declines because of decreasing proangiogenic factor secretion. This could restrict the effectiveness of autologous cell therapy with ADSCs in aged patients.

  12. Twenty-seven years of phase III trials for patients with extensive disease small-cell lung cancer: disappointing results.

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    Isao Oze

    Full Text Available BACKGROUND: Few studies have formally assessed whether treatment outcomes have improved substantially over the years for patients with extensive disease small-cell lung cancer (ED-SCLC enrolled in phase III trials. The objective of the current investigation was to determine the time trends in outcomes for the patients in those trials. METHODS AND FINDINGS: We searched for trials that were reported between January 1981 and August 2008. Phase III randomized controlled trials were eligible if they compared first-line, systemic chemotherapy for ED-SCLC. Data were evaluated by using a linear regression analysis. RESULTS: In total, 52 trials were identified that had been initiated between 1980 and 2006; these studies involved 10,262 patients with 110 chemotherapy arms. The number of randomized patients and the proportion of patients with good performance status (PS increased over time. Cisplatin-based regimens, especially cisplatin and etoposide (PE regimen, have increasingly been studied, whereas cyclophosphamide, doxorubicin, and vincristine-based regimens have been less investigated. Multiple regression analysis showed no significant improvement in survival over the years. Additionally, the use of a PE regimen did not affect survival, whereas the proportion of patients with good PS and the trial design of assigning prophylactic cranial irradiation were significantly associated with favorable outcome. CONCLUSIONS AND SIGNIFICANCE: The survival of patients with ED-SCLC enrolled in phase III trials did not improve significantly over the years, suggesting the need for further development of novel targets, newer agents, and comprehensive patient care.

  13. Non-traumatic spontaneous acute epidural hematoma in a patient with sickle cell disease.

    Science.gov (United States)

    Serarslan, Yurdal; Aras, Mustafa; Altaş, Murat; Kaya, Hasan; Urfalı, Boran

    2014-01-01

    A 19-year-old female with sickle cell anemia (SCD) was referred to our hospital after two days of hospitalization at another hospital for a headache crisis. This headache crisis was due to a raised intracranial pressure; these symptoms were noted and included in her comprehensive list of symptoms. There was an acute drop in the hemoglobin and hematocrit levels. The cranial CT scan demonstrated a left fronto-parietal acute epidural hematoma (AEH) and a calvarial bone expansion, which was suggestive of medullary hematopoiesis. The patient underwent emergent craniotomy and evacuation of the hematoma. There were no abnormal findings intra-operatively apart from the AEH, except skull thickening and active petechial bleeding from the dural arteries. Repeated CT scan showed a complete evacuation of the hematoma. The possible underlying pathophysiological mechanisms were discussed. In addition to the factors mentioned in the relevant literature, any active petechial bleeding from the dural arteries on the separated surface of the dura from the skull could have contributed to the expanding of the AEH in our patient. Neurosurgeons and other health care providers should be aware of spontaneous AEH in patients with SCD. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  14. Quality of life of patients with graft-versus-host disease (GvHD post-hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Sibéli de Fátima Ferraz Simão Proença

    Full Text Available Abstract OBJECTIVE Assessing the quality of life of adult patients with hematological cancer in the 100 days after transplantation of hematopoietic stem cells and verifying whether the variable graft-versus-host disease (GvHD is predictive of worse results. METHOD An observational correlational and quantitative study with 36 adult participants diagnosed with hematologic cancer who underwent hematopoietic stem cell transplantation from September 2013 to June 2015. RESULT The mean age was 37 years, 52.78% were female, and 61.11% were diagnosed with leukemia. Quality of life scores showed a significant impact between pre-transplantation and pre-hospital discharge, and also within the 100 days post-transplantation. The statistical analysis between the scores for the groups with and without GvHD showed a significant difference between the presence of the complication and worse results. CONCLUSION Quality of life is altered as a result of hematopoietic stem cells transplantation, especially in patients who have graft-versus-host disease.

  15. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Ra Jeong Chan

    2011-10-01

    Full Text Available Abstract Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here.

  16. CD209-336A/G promotor polymorphism and its clinical associations in sickle cell disease Egyptian Pediatric patients.

    Science.gov (United States)

    Afifi, Rasha Abdel-Raouf; Kamal, Dina; Sayed, Riham El; Ekladious, Sherif M M; Shaheen, Gehan H; Yousry, Sherif M; Hussein, Rania Elsayed

    2018-06-01

    To detect the frequency of CD209 A>G polymorphism in sickle cell disease (SCD) Egyptian patients and to evaluate the use of CD209 A>G polymorphism as a genetic predictor of SCD clinical heterogeneity. A total of 100 Egyptian children with SCD and 100 Egyptian controls were tested for CD209 A>G polymorphism and were followed up prospectively between June 2012 and December 2014. Comparison of CD209 A>G polymorphism among cases and controls did not show statistically significant difference (p = .742). In addition, comparison of the allelic frequency did not show statistically significant difference (p = .738). Infections occurred more frequently among the heterozygous genotype (AG; 60.5%) and homozygous genotype (GG; 75%) patients than among the wild (AA) genotype (24.1%; p G polymorphism. Infections occurred more frequently among the heterozygous genotype (AG) and homozygous genotype (GG) patients. Copyright © 2017. Published by Elsevier Ltd.

  17. Free tissue transfer in patients with sickle cell disease: Considerations for multi-disciplinary peri-operative management.

    Science.gov (United States)

    Cooper, Lilli; Seth, Rohit; Rhodes, Elizabeth; Alousi, Mohammed; Sivakumar, Bran

    2017-01-01

    Sickle cell disease (SCD) is an increasingly common condition in the UK. The safety of free tissue transfer in these patients is controversial, and no specific guidelines exist. The aim of this paper is to create recommendations for the plastic surgical multidisciplinary team for use in the assessment and management of SCD patients undergoing free tissue transfer and reconstruction. A literature review was performed in PubMed of 'sickle [TiAb] AND plast* adj3 surg*. Sickle cell disease is explained, as is the relative peri-operative risk in different genotypes of SCD. Acute and chronic manifestations of SCD are described by system, for consideration at pre-operative assessment and post-operative review. The evidence surrounding free tissue transfer and SCD is discussed and the outcomes in published cases summarised. An algorithm for peri-operative multi-disciplinary management is outlined and justified. Free tissue transfer theoretically carries a high risk of a crisis, due not only to long anaesthetic times, but the potential requirement for tourniquet use, and the relatively hypoxic state of the transferred tissue. This paper outlines a useful, practical algorithm to optimise the safety of free tissue transfer in patients with SCD. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy.

    Science.gov (United States)

    ElAlfy, Mohsen Saleh; Adly, Amira Abdel Moneam; Ebeid, Fatma Soliman ElSayed; Eissa, Deena Samir; Ismail, Eman Abdel Rahman; Mohammed, Yasser Hassan; Ahmed, Manar Elsayed; Saad, Aya Sayed

    2018-06-20

    Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4 + CD28 null T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4 + CD28 null T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4 + CD28 null T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4 + CD28 null T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4 + CD28 null T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4 + CD28 null T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4 + CD28 null T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.

  19. Early recovery of circulating immature B cells in B-lymphoblastic leukemia patients after CD19 targeted CAR T cell therapy: A pitfall for minimal residual disease detection.

    Science.gov (United States)

    Xiao, Wenbin; Salem, Dalia; McCoy, Catharine S; Lee, Daniel; Shah, Nirali N; Stetler-Stevenson, Maryalice; Yuan, Constance M

    2017-09-09

    CD19-targeted chimeric-antigen receptor-modified T-cells (CAR-T) are promising in the treatment of refractory B-lymphoblastic leukemia (B-ALL). Minimal residual disease (MRD) detection by multicolor flow cytometry (FCM) is critical to distinguish B-ALL MRD from regenerating, non-neoplastic B-cell populations. FCM was performed on samples from 9 patients with B-ALL treated with CAR-T. All 9 patients showed response to CAR-T. Additionally, FCM revealed circulating CD10 + B cells, potentially mimicking MRD. Circulating CD10+ B-cells were detected in blood from 3 days to 3 months after CAR-T, comprising 73% (median) of B-cells (52-83%, 95%CI). They expressed CD19, CD10, CD20, bright CD9, CD22, CD24, moderate CD38 and dim CD58, but were CD34 (-), with bright CD45 and polyclonal surface light chain immunoglobulin (sIg) expression. A similar CD10 + B-cell subpopulation was detected by marrow FCM, amidst abundant B-cell precursors. These circulating CD10 + B-cells are compatible with immature B-cells, and are a reflection of B-cell recovery within the marrow. They are immunophenotypically distinguishable from residual B-ALL. Expression of light chain sIg and key surface antigens characterizing regenerating B-cell precursors can distinguish immature B-cells from B-ALL MRD and prevent misdiagnosis. © 2017 International Clinical Cytometry Society. © 2017 International Clinical Cytometry Society.

  20. Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease

    DEFF Research Database (Denmark)

    Lovato, Paola; Brender, Christine; Agnholt, Jørgen

    2003-01-01

    Via cytoplasmic signal transduction pathways, cytokines induce a variety of biological responses and modulate the outcome of inflammatory diseases and malignancies. Crohn's disease is a chronic inflammatory bowel disease of unknown etiology. Perturbation of the intestinal cytokine homeostasis is ...

  1. Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure

    Directory of Open Access Journals (Sweden)

    Yoga Yuniadi

    2016-01-01

    Full Text Available Background. Proangiogenic Hematopoietic Cells (PHC which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4±7.40 yo preimplant NT proBNP level is 5124.5±4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87±0.41, 0.63±0.66, 99.00±2.60, and 3.22±3.79%, respectively. LVEF was improved (22±5.68 versus 26.8±7.93, p<0.001 during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity.

  2. The Impact of Coexisting Asthma, Chronic Obstructive Pulmonary Disease and Tuberculosis on Survival in Patients with Lung Squamous Cell Carcinoma.

    Science.gov (United States)

    Huang, Jing-Yang; Jian, Zhi-Hong; Ndi Nfor, Oswald; Jhang, Kai-Ming; Ku, Wen-Yuan; Ko, Pei-Chieh; Jan, Shiou-Rung; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Liang, Yu-Chiu; Liaw, Yung-Po

    2015-01-01

    Pulmonary diseases [asthma, chronic obstructive pulmonary disease (COPD), and tuberculosis (TB)] are associated with lung cancer mortality. However, the relationship between coexisting pulmonary diseases and survival in patients with lung squamous cell carcinoma (SqCC) has not been well defined. Patients newly diagnosed with SqCC between 2003 and 2008 were identified by linking the National Health Insurance Research Database and Taiwan Cancer Registry Database. Cases with SqCC were followed up until death, loss to follow-up, or study end in 2010. Information on health status, date of death and the main causes of death was ascertained from the National Death Registry Database. Cox proportional hazard regression was used to calculate the hazard ratio (HR) of coexisting asthma, COPD and/or TB. During the study period, a total of 5406 cases with SqCC were enrolled. For all cause-mortality, HRs were 1.08 [95% confidence interval (CI), 0.99-1.18], 1.04 (95% CI, 0.97-1.12), and 1.14 (95% CI, 1.00-1.31) for individuals with asthma, COPD, and TB, respectively. Specifically, among men with coexisting pulmonary diseases, the HRs were 1.56 (95% CI, 1.23-1.97) and 1.11 (95% CI, 1.00-1.24) for individuals with asthma+COPD+TB and asthma+COPD, respectively. Among male patients with stage III SqCC, HRs were 3.41 (95%CI, 1.27-9.17) and 1.65 (95%CI, 1.10-2.47) for individuals with asthma+TB and asthma+COPD+TB, respectively. Among male patients with stage IV SqCC, HRs were 1.40 (95%CI, 1.00-1.97) and 1.25 (95%CI, 1.03-1.52) for individuals with asthma+ COPD+TB and asthma. Among female patients with stage I and II, HR was 0.19 (95%CI, 005-0.77) for individuals with asthma. Coexisting pulmonary diseases increased the risk of mortality from SqCC in male patients. For female patients with early stage SqCC, pre-existing asthma decreased mortality. These patients deserve greater attention while undergoing cancer treatment.

  3. The Impact of Coexisting Asthma, Chronic Obstructive Pulmonary Disease and Tuberculosis on Survival in Patients with Lung Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Jing-Yang Huang

    Full Text Available Pulmonary diseases [asthma, chronic obstructive pulmonary disease (COPD, and tuberculosis (TB] are associated with lung cancer mortality. However, the relationship between coexisting pulmonary diseases and survival in patients with lung squamous cell carcinoma (SqCC has not been well defined.Patients newly diagnosed with SqCC between 2003 and 2008 were identified by linking the National Health Insurance Research Database and Taiwan Cancer Registry Database. Cases with SqCC were followed up until death, loss to follow-up, or study end in 2010. Information on health status, date of death and the main causes of death was ascertained from the National Death Registry Database. Cox proportional hazard regression was used to calculate the hazard ratio (HR of coexisting asthma, COPD and/or TB.During the study period, a total of 5406 cases with SqCC were enrolled. For all cause-mortality, HRs were 1.08 [95% confidence interval (CI, 0.99-1.18], 1.04 (95% CI, 0.97-1.12, and 1.14 (95% CI, 1.00-1.31 for individuals with asthma, COPD, and TB, respectively. Specifically, among men with coexisting pulmonary diseases, the HRs were 1.56 (95% CI, 1.23-1.97 and 1.11 (95% CI, 1.00-1.24 for individuals with asthma+COPD+TB and asthma+COPD, respectively. Among male patients with stage III SqCC, HRs were 3.41 (95%CI, 1.27-9.17 and 1.65 (95%CI, 1.10-2.47 for individuals with asthma+TB and asthma+COPD+TB, respectively. Among male patients with stage IV SqCC, HRs were 1.40 (95%CI, 1.00-1.97 and 1.25 (95%CI, 1.03-1.52 for individuals with asthma+ COPD+TB and asthma. Among female patients with stage I and II, HR was 0.19 (95%CI, 005-0.77 for individuals with asthma.Coexisting pulmonary diseases increased the risk of mortality from SqCC in male patients. For female patients with early stage SqCC, pre-existing asthma decreased mortality. These patients deserve greater attention while undergoing cancer treatment.

  4. Patent Foramen Ovale in Patients with Sickle Cell Disease and Stroke: Case Presentations and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sheila Razdan

    2013-01-01

    Full Text Available Although individuals with sickle cell disease (SCD are at increased risk for stroke, the underlying pathophysiology is incompletely understood. Intracardiac shunting via a patent foramen ovale (PFO is associated with cryptogenic stroke in individuals without SCD. Recent evidence suggests that PFOs are associated with stroke in children with SCD, although the role of PFOs in adults with stroke and SCD is unknown. Here, we report 2 young adults with SCD, stroke, and PFOs. The first patient had hemoglobin SC and presented with a transient ischemic attack and a subsequent ischemic stroke. There was no evidence of cerebral vascular disease on imaging studies and the PFO was closed. The second patient had hemoglobin SS and two acute ischemic strokes. She had cerebral vascular disease with moyamoya in addition to a peripheral deep venous thrombosis (DVT. Chronic transfusion therapy was recommended, and the DVT was managed with warfarin. The PFO was not closed, and the patients' neurologic symptoms were stabilized. We review the literature on PFOs and stroke in SCD. Our cases and the literature review illustrate the dire need for further research to evaluate PFO as a potential risk factor for stroke in adults with SCD.

  5. Sickle Cell Disease

    Science.gov (United States)

    ... days. Your body may have trouble making enough new cells to replace the ones that you lost. Because ... Indian backgrounds. What are the symptoms of sickle cell disease? People with ... the whites of the eyes (icterus) The effects of SCD vary from person ...

  6. Early disease progression in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy.

    Science.gov (United States)

    Yamaguchi, Motoko; Suzuki, Ritsuro; Kim, Seok Jin; Ko, Young Hyeh; Oguchi, Masahiko; Asano, Naoko; Miyazaki, Kana; Terui, Yasuhiko; Kubota, Nobuko; Maeda, Takeshi; Kobayashi, Yukio; Amaki, Jun; Soejima, Toshinori; Saito, Bungo; Shimoda, Emiko; Fukuhara, Noriko; Tsukamoto, Norifumi; Shimada, Kazuyuki; Choi, Ilseung; Utsumi, Takahiko; Ejima, Yasuo; Kim, Won Seog; Katayama, Naoyuki

    2018-03-30

    Prognosis of patients with localized nasal extranodal natural killer/T-cell lymphoma, nasal type (ENKL) has been improved by non-anthracycline-containing treatments such as concurrent chemoradiotherapy (CCRT). However, some patients experience early disease progression. To clarify the clinical features and outcomes of these patients, data from 165 patients with localized nasal ENKL who were diagnosed between 2000 and 2013 at 31 institutes in Japan and who received radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) were retrospectively analyzed. Progression of disease within 2 years after diagnosis (POD24) was used as the definition of early progression. An independent dataset of 60 patients with localized nasal ENKL who received CCRT at Samsung Medical Center was used in the validation analysis. POD24 was documented in 23% of patients who received RT-DeVIC and in 25% of patients in the validation cohort. Overall survival (OS) from risk-defining events of the POD24 group was inferior to that of the reference group in both cohorts (P < .00001). In the RT-DeVIC cohort, pretreatment elevated levels of serum soluble interleukin-2 receptor (sIL-2R), lactate dehydrogenase, C-reactive protein, and detectable Epstein-Barr virus DNA in peripheral blood were associated with POD24. In the validation cohort, no pretreatment clinical factor associated with POD24 was identified. Our study indicates that POD24 is a strong indicator of survival in localized ENKL, despite the different CCRT regimens adopted. In the treatment of localized nasal ENKL, POD24 is useful for identifying patients who have unmet medical needs. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. Effects of vaccines in patients with sickle cell disease: a systematic review protocol.

    Science.gov (United States)

    Wiyeh, Alison Beriliy; Abdullahi, Leila Hussein; Wonkam, Ambroise; Wiysonge, Charles Shey; Kaba, Mamadou

    2018-03-25

    Sickle cell disease (SCD) is an inherited haematological disorder caused by a single point mutation (Glub6Val) that promotes polymerisation of haemoglobin S and sickling of erythrocytes. Inflammation, haemolysis, microvascular obstruction and organ damage characterise the highly variable clinical expression of SCD. People with SCD are at increased risk of severe infections, hence the need for vaccination against common disease-causing organisms in this population. We aim to review the evidence on the efficacy and safety of vaccines in people with SCD. The present systematic review will examine the current data as indexed in PubMed, CENTRAL, EMBASE and EBSCOHost. We will consult Strategic Advisory Group of Experts practice statements, conference abstracts, reference lists of relevant articles, WHO ICTRP trial registry and experts in the field. Two authors will independently screen search outputs, select studies, extract data and assess risk of bias; resolving discrepancies by discussion and consensus between the two authors or arbitration by a third author when necessary. We will perform a meta-analysis for clinically homogenous studies. Evidence from clinically diverse studies will be aggregated using narrative synthesis of the findings. In either case, we will use the GRADE approach to assess the strength of the available evidence. The study draws on data that are readily available in the public domain, hence no formal ethical review and approval is required. The findings of this review will be disseminated through conference presentations and a publication in a peer-reviewed journal. CRD42018084051. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Regional cerebral blood flow in patients with sickle cell disease: study with single photon emission computed tomography

    International Nuclear Information System (INIS)

    Al-Kandari, F.A.; Owunwanne, A.; Syed, G.M.; Elgazzar, A.H.; Rizui, A.M.; Al-Ajmi, J.A.; Mohammed, A.M.; Ar Marouf, R.; Shiekh, M.

    2007-01-01

    Neurological complications have been reported in patients with sickle-cell disease (SCD) using positron emission tomography (PET), magnetic resonance imaging (MRI), and computed tomography (CT), but not with single photon emission computed tomography (SPECT). The objective of this study was to investigate brain perfusion in the patients with SCD using SPECT after technetium-99m hexamethylpropylene amine oxime ( 99m Tc-HMPAO), was administered and compare the findings with those of demography, physical examination, MRI and hematological profile. The study involved 21 patients (12 males, 9 females, age at study 8-45 years) who were known to be having SCD for a duration of at least 5 years. The patients were not in acute crisis and had normal neurological assessments with no known history of stroke or transient ischemic episode or previous abnormal CT or MRI brain scan, and were right-handed. The brain SPECT was performed after intravenous injection of 740 MBq (20 mCi) 99m Tc-HMPAO in adults or an appropriate dose in pediatric patients. The scans were visually interpreted by two nuclear medicine physicians and a decision was reached by consensus. An MRI done 3 months later was interpreted by a radiologist. The demographic data and hematological profile were obtained from the medical records of the patients. Of the 21 patients, 7 (age 11-22 years) had brain perfusion deficit mostly in the frontal lobe either alone or in combination with temporal and/or parietal lobe. The MRI was abnormal in 2 patients. The brain perfusion deficit was not associated with the demographic data of the patients or hematological profiles. The findings show that SPECT was useful in detecting brain perfusion deficit in SCD patients, and such an early detection may be clinically useful in the subsequent follow-up of such patients, since it is known that cerebral perfusion deficit can lead to silent infarct and/or overt stroke, and affect cognitive skills. (author)

  9. Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Yingchun Wang

    2015-01-01

    Full Text Available Sickle cell nephropathy (SCN is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI. Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+ was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2 rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies.

  10. Flow cytometry analysis of T-cell subsets in cerebrospinal fluid of narcolepsy type 1 patients with long-lasting disease

    DEFF Research Database (Denmark)

    Moresco, Monica; Lecciso, Mariangela; Ocadlikova, Darina

    2018-01-01

    BACKGROUND: Type 1 narcolepsy (NT1) is a central hypersomnia linked to the destruction of hypocretin-producing neurons. A great body of genetic and epidemiological data points to likely autoimmune disease aetiology. Recent reports have characterized peripheral blood T-cell subsets in NT1, whereas...... data regarding the cerebrospinal fluid (CSF) immune cell composition are lacking. The current study aimed to characterize the T-cell and natural killer (NK) cell subsets in NT1 patients with long disease course. METHODS: Immune cell subsets from CSF and peripheral blood mononuclear cell (PBMC) samples...... were analysed by flow cytometry in two age-balanced and sex-balanced groups of 14 NT1 patients versus 14 healthy controls. The frequency of CSF cell groups was compared with PBMCs. Non-parametric tests were used for statistical analyses. RESULTS: The NT1 patients did not show significant differences...

  11. Imaging of sickle cell disease

    International Nuclear Information System (INIS)

    Crowley, J.J.; Sarnaik, S.

    1999-01-01

    Sickle cell disease is an important health care issue in the United States and in certain areas in Africa, the Middle East and India. Although a great deal of progress has been made in understanding the disease at the molecular and pathophysiologic level, specific treatment which is safe and accessible for most patients is still elusive. Going into the next millennium, the management of this disease is still largely dependent on early diagnosis and the treatment of complications with supportive care. Thus, diagnosis and evaluation of the complications of the disease are crucial in directing clinical care at the bedside. Modern imaging modalities have greatly improved, and their application in the patient with the sickling disorders has enhanced the decision - making process. The purpose of this article is to review the clinical aspects of common complications of the disease and to discuss imaging approaches which are useful in their evaluation. (orig.)

  12. Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings.

    Science.gov (United States)

    Hedin, Charlotte R; McCarthy, Neil E; Louis, Petra; Farquharson, Freda M; McCartney, Sara; Taylor, Kirstin; Prescott, Natalie J; Murrells, Trevor; Stagg, Andrew J; Whelan, Kevin; Lindsay, James O

    2014-10-01

    Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups. Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenotype by flow cytometry and IP by differential lactulose-rhamnose absorption in 22 patients with inactive CD, 21 of their healthy siblings and 25 controls. Subject's genotype relative risk was determined by Illumina Immuno BeadChip. Strikingly, siblings shared aspects of intestinal dysbiosis with patients with CD (lower concentrations of Faecalibacterium prausnitzii (p=0.048), Clostridia cluster IV (p=0.003) and Roseburia spp. (p=0.09) compared with controls). As in CD, siblings demonstrated a predominance of memory T cells (p=0.002) and elevated naïve CD4 T cell β7 integrin expression (p=0.01) compared with controls. FC was elevated (>50 μg/g) in 8/21 (38%) siblings compared with 2/25 (8%) controls (p=0.028); whereas IP did not differ between siblings and controls. Discriminant function analysis determined that combinations of these factors significantly discriminated between groups (χ(2)=80.4, df=20, pmicrobiological variables. Healthy siblings of patients with CD manifest immune and microbiological abnormalities associated with CD distinct from their genotype-related risk and provide an excellent model in which to investigate early CD pathogenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Prognostic role of patient gender in limited-disease small-cell lung cancer treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    Roengvoraphoj, Olarn; Eze, Chukwuka; Niyazi, Maximilian; Li, Minglun; Belka, Claus; Manapov, Farkhad; Hildebrandt, Guido; Fietkau, Rainer

    2017-01-01

    Previous studies have demonstrated that female gender could be a prognostic factor in limited-disease (LD) small-cell lung cancer (SCLC), but the correlation between patient gender and survival parameters remains unclear. Data from 179 LD SCLC patients treated with definitive chemoradiotherapy (CRT) were reviewed. Influence of patient gender on time to progression (TTP), local control (LC), brain metastasis-free (BMFS), distant metastasis-free (DMFS) and overall survival (OS) was analysed. Definitive CRT was completed by 179 (110 men/69 women) patients. Of these, 68 (38%; 34 men/34 women) patients were treated in concurrent and 111 (62%; 76 men/35 women) in sequential mode. Prophylactic cranial irradiation (PCI) was subsequently applied in 70 (39%; 36 men/34 women) patients with partial or complete response after CRT. Median OS was 20 (95% confidence interval [CI] 10-22) and 14 (95% CI 10-18) months in female and male patients, respectively (p = 0.021). In subgroups defined by remission status (complete and partial response) after CRT, an OS benefit for females compared to males was also detected. There was no correlation between patient gender and TTP, LC or DMFS, and no difference in OS in the female and male subgroups treated with PCI. The incidence of metachronous brain metastases (BMs) in the male and female subgroups differed significantly (40/110 men vs. 18/69 women, p = 0.03). Also, mean BMFS was significantly longer in women (p = 0.023). Patient gender also significantly correlated with OS on multivariate analysis after adjustment for other prognostic factors (p = 0.04, HR 1.38, 95% CI 1.08-1.92). In this heterogeneous LD SCLC patient cohort treated with definitive CRT, female gender was significantly associated with longer BMFS and OS, as well as with a lower incidence of metachronous brain failure. (orig.) [de

  14. The safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel in the treatment of non-small cell lung cancer patients with interstitial lung disease.

    Science.gov (United States)

    Yasuda, Yuichiro; Hattori, Yoshihiro; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Urata, Yoshiko; Nogami, Munenobu; Takenaka, Daisuke; Negoro, Shunichi; Satouchi, Miyako

    2018-01-01

    The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  15. Sperm, nuclear, phospholipid, and red blood cell antibodies and isotype RF in infertile couples and patients with autoimmune rheumatic diseases.

    Science.gov (United States)

    Fichorova, R; Nakov, L; Baleva, M; Nikolov, K; Gegova, I

    1996-12-01

    To determine if measuring of nonorgan-specific autoantibodies is useful for better understanding and management of unexplained infertility. Sera were obtained from 70 infertile couples, 57 rheumatic patients, and 76 fertile donors. Sperm antibodies (SA) were detected by the tests of Kibrick and Friberg, anti-histones, anti-cardiolipin antibodies, and RF isotypes by ELISA, antinuclear antibodies by indirect immunofluorescence, and anti-red blood cell antibodies by Capture-R. Multiple autoimmune reactivity (both partners positive and/or more than one type of autoantibody involved), higher than naturally occurring in fertile individuals, was found in 55% of the idiopathically infertile couples. IgA-RF was the dominant autoimmune marker. SA revealed similar rates in patients with rheumatic diseases and in infertiles with or without other autoantibodies. Although no single autoimmunity marker could predict occurrence of SA, the coincidence of enhanced polyclonal autoimmunity in both partners of infertile couples might potentiate their negative effect on reproduction.

  16. Flow cytometry analysis of T-cell subsets in cerebrospinal fluid of narcolepsy type 1 patients with long-lasting disease.

    Science.gov (United States)

    Moresco, Monica; Lecciso, Mariangela; Ocadlikova, Darina; Filardi, Marco; Melzi, Silvia; Kornum, Birgitte Rahbek; Antelmi, Elena; Pizza, Fabio; Mignot, Emmanuel; Curti, Antonio; Plazzi, Giuseppe

    2018-04-01

    Type 1 narcolepsy (NT1) is a central hypersomnia linked to the destruction of hypocretin-producing neurons. A great body of genetic and epidemiological data points to likely autoimmune disease aetiology. Recent reports have characterized peripheral blood T-cell subsets in NT1, whereas data regarding the cerebrospinal fluid (CSF) immune cell composition are lacking. The current study aimed to characterize the T-cell and natural killer (NK) cell subsets in NT1 patients with long disease course. Immune cell subsets from CSF and peripheral blood mononuclear cell (PBMC) samples were analysed by flow cytometry in two age-balanced and sex-balanced groups of 14 NT1 patients versus 14 healthy controls. The frequency of CSF cell groups was compared with PBMCs. Non-parametric tests were used for statistical analyses. The NT1 patients did not show significant differences of CSF immune cell subsets compared to controls, despite a trend towards higher CD4 + terminally differentiated effector memory T cells. T cells preferentially displayed a memory phenotype in the CSF compared to PBMCs. Furthermore, a reduced frequency of CD4 + terminally differentiated effector memory T cells and an increased frequency of NK CD56 bright cells was observed in PBMCs from patients compared to controls. Finally, the ratio between CSF and peripheral CD4 + terminally differentiated effector memory T cells was two-fold increased in NT1 patients versus controls. Significant differences in PBMCs and in CSF/PBMC ratios of immune cell profile were found in NT1 patients compared to healthy controls. These differences might have arisen from the different HLA status, or be primary or secondary to hypocretin deficiency. Further functional studies in patients close to disease onset are required to understand NT1 pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Progressive rise in red blood cell distribution width predicts mortality and cardiovascular events in end-stage renal disease patients.

    Science.gov (United States)

    Yoon, Hye Eun; Kim, Sung Jun; Hwang, Hyeon Seok; Chung, Sungjin; Yang, Chul Woo; Shin, Seok Joon

    2015-01-01

    Red blood cell distribution width (RDW) is a robust marker of adverse clinical outcomes in various populations. However, the clinical significance of a progressive rise in RDW is undetermined in end-stage renal disease (ESRD) patients. The purpose of this study was to determine the prognostic importance of a change in RDW in ESRD patients. Three hundred twenty-six incident dialysis patients were retrospectively analyzed. Temporal changes in RDW during 12 months after dialysis initiation were assessed by calculating the coefficients by linear regression. Patients were divided into two groups: an RDW-decreased group who had negative coefficient values (n = 177) and an RDW-increased group who had positive values (n = 149). The associations between rising RDW and mortality and cardiovascular (CV) events were investigated. During a median follow-up of 2.7 years (range, 1.0-7.7 years), 75 deaths (24.0%) and 60 non-fatal CV events (18.4%) occurred. The event-free survival rate for the composite of end-points was lower in the RDW-increased group (P = 0.004). After categorizing patients according to baseline RDW, the event-free survival rate was lowest in patients with a baseline RDW >14.9% and increased RDW, and highest in patients with a baseline RDW ≤14.9% and decreased RDW (P = 0.02). In multivariate analysis, rising RDW was independently associated with the composite of end-points (hazard ratio = 1.75, P = 0.007), whereas the baseline RDW was not. This study shows that a progressive rise in RDW independently predicted mortality and CV events in ESRD patients. Rising RDW could be an additive predictor for adverse CV outcomes ESRD patients.

  18. Comparison of endothelial progenitor cells in Parkinson's disease patients treated with levodopa and levodopa/COMT inhibitor.

    Directory of Open Access Journals (Sweden)

    Phil Hyu Lee

    Full Text Available BACKGROUND: Levodopa treatment in Parkinson's disease (PD increases in serum homocysteine levels due to its metabolism via catechol O-methyltransferase. Endothelial progenitor cells (EPCs have the capacity to differentiate into mature endothelial cells and are markers for endothelial functions and cardiovascular risks. Along with traditional vascular risk factors, hyperhomocysteinemia is known to decrease the level of EPCs. In the present study, we hypothesized that that levodopa-induced hyperhomocysteinemia leads to a change in EPC levels. METHODOLOGY/PRINCIPAL FINDINGS: We prospectively enrolled PD patients who had been prescribed either levodopa/carbidopa (PD-L group, n = 28 or levodopa/carbidopa/COMT inhibitor (PD-LC group, n = 25 for more than 1 year. The number of circulating EPCs was measured by flow cytometry using dual staining of anti-CD34 and anti-KDR antibodies. The EPCs were divided into tertiles based on their distributions and a logistic regression analysis was used to estimate independent predictors of the highest tertile of EPCs. The number of endothelial progenitor cells was significantly decreased in PD-L patients (118±99/mL compared with either PD-LC patients (269±258/mL, p = 0.007 or controls (206±204/mL, p = 0.012. The level of homocysteine was significantly increased in PD-L patients (14.9±5.3 µmol/L compared with either PD-LC patients (11.9±3.0 µmol/L, p = 0.028 or controls (11.1±2.5 µmol/L, p = 0.012. The level of homocysteine was negatively correlated with endothelial progenitor cell levels (r = -0.252, p = 0.028 and was an independent predictor of the highest tertile of endothelial progenitor cell levels (OR; 0.749 [95% CI: 0.584-0.961]. CONCLUSIONS/SIGNIFICANCE: These data indicate that a higher consumption of EPC for restoration of endothelial damage may be associated with chronic levodopa treatment in PD patients.

  19. The Birmingham Vasculitis Activity Score as a Measure of Disease Activity in Patients with Giant Cell Arteritis

    Science.gov (United States)

    Kermani, TA; Cuthbertson, D; Carette, S; Hoffman, GS; Khalidi, NA; Koening, CL; Langford, CA; McKinnon-Maksimowicz, K; McAlear, CA; Monach, PA; Seo, P; Warrington, KJ; Ytterberg, SR; Merkel, PA; Matteson, EL

    2016-01-01

    Objective To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) in the assessment of disease activity in giant cell arteritis (GCA). Methods Patients with GCA enrolled in a prospective, multicenter, longitudinal study with symptoms of active vasculitis during any visit were included. Spearman’s rank correlation was used to explore the association of the BVAS with other measures of disease activity. Results During a mean (SD) follow-up of 2.3 (1.6) years, symptoms of active GCA were present in 236 visits in 136 subjects (100 female, 74%). Median (range) BVAS1 (new/worse symptoms) was 1 (0–10) and median (range) BVAS2 (persistent symptoms) was 0 (0–5). Median (range) physician global assessment (PGA) was 4 (0–9) for disease activity in the past 28 days and 2 (0–9) for activity on the day of the visit. Important ischemic manifestations of active vasculitis not captured by the BVAS included tongue/jaw claudication (27%), upper extremity claudication (15%), lower extremity claudication (5%), carotidynia (7%), ischemic retinopathy (5%). During 25 visits (11%) with active disease, all symptoms of active vasculitis were captured in the “Other” category yet still resulted in a BVAS 1 and BVAS 2 of 0. BVAS1 moderately correlated with PGA for the past 28 days (Spearman’s correlation 0.50) and physician-rated disease activity for the past 28 days (Spearman’s correlation 0.46). Conclusions The BVAS has limited utility in GCA. Patients with active GCA can have a BVAS of 0. Many important ischemic symptoms attributable to active vasculitis are not captured in the composite score. PMID:27036388

  20. Impact of chronic obstructive pulmonary disease on postoperative recurrence in patients with resected non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Qiang GL

    2015-12-01

    Full Text Available Guangliang Qiang, Chaoyang Liang, Fei Xiao, Qiduo Yu, Huanshun Wen, Zhiyi Song, Yanchu Tian, Bin Shi, Yongqing Guo, Deruo Liu Department of Thoracic Surgery, China–Japan Friendship Hospital, Beijing, People’s Republic of China Purpose: This study aimed to determine whether the severity of chronic obstructive pulmonary disease (COPD affects recurrence-free survival in non-small-cell lung cancer (NSCLC patients after surgical resection.Patients and methods: A retrospective study was performed on 421 consecutive patients who had undergone lobectomy for NSCLC from January 2008 to June 2011. Classification of COPD severity was based on guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD. Characteristics among the three subgroups were compared and recurrence-free survivals were analyzed.Results: A total of 172 patients were diagnosed with COPD (124 as GOLD-1, 46 as GOLD-2, and two as GOLD-3. The frequencies of recurrence were significantly higher in patients with higher COPD grades (P<0.001. Recurrence-free survival at 5 years was 78.1%, 70.4%, and 46.4% in non-COPD, mild COPD, and moderate/severe COPD groups, respectively (P<0.001. By univariate analysis, the age, sex, smoking history, COPD severity, tumor size, histology, and pathological stage were associated with recurrence-free survival. Multivariate analysis showed that older age, male, moderate/severe COPD, and advanced stage were independent risk factors associated with recurrence-free survival.Conclusion: NSCLC patients with COPD are at high risk for postoperative recurrence, and moderate/severe COPD is an independent unfavorable prognostic factor. Keywords: lung neoplasms, surgery, pulmonary function test, prognosis

  1. The dynamic change of endothelial cell, endothelin and 6-K-PGF1α in circulating blood of the patients with coronary heart disease

    International Nuclear Information System (INIS)

    Xia Zhiyun; Wang Linglin; Zou Songhai

    1995-01-01

    With the circulating endothelial cell (CEC) as an indicator of vessel endothelial cell (VEC) injury, and plasma endothelin (ET) and prostaglandin F 1α (PGI 2 ) reflecting the functional change of the VEC, a comparative study between 85 patients with coronary heart disease and 30 normal health, and also a dynamic observation of 50 patients with unstable angina pectoris and 20 patients with acute myocardial infarction (AMI) were reported. The result showed that in patients with coronary heart disease, peripheral blood circulating CEC and ET level was increased (P 2 decreased (P<0.01). All these were more significant in patients with unstable angina pectoris and myocardial infarction, and its magnitude correlated closely with the severity of the disease. All these showed that the VEC injury and the imbalance of its endothelial relaxing and contracting factors have played an important role in the pathogenesis of coronary heart disease

  2. Continuous Manual Exchange Transfusion for Patients with Sickle Cell Disease: An Efficient Method to Avoid Iron Overload.

    Science.gov (United States)

    Koehl, Bérengère; Missud, Florence; Holvoet, Laurent; Ithier, Ghislaine; Sakalian-Black, Oliver; Haouari, Zinedine; Lesprit, Emmanuelle; Baruchel, André; Benkerrou, Malika

    2017-03-14

    Children with sickle cell anemia (SCA) may be at risk of cerebral vasculopathy and strokes, which can be prevented by chronic transfusion programs. Repeated transfusions of packed red blood cells (PRBCs) is currently the simplest and most used technique for chronic transfusion programs. However, iron overload is one of the major side effects of this therapy. More developed methods exist, notably the apheresis of RBC (erythrapheresis), which is currently the safest and most efficient method. However, it is costly, complicated, and cannot be implemented everywhere, nor is it suitable for all patients. Manual exchange transfusions combine one or more manual phlebotomies with a PRBC transfusion. At the Reference Center of Sickle Cell Disease, we set up a continuous method of manual exchange transfusion that is feasible for all hospital settings, demands no specific equipment, and is widely applicable. In terms of HbS decrease, stroke prevention, and iron overload prevention, this method showed comparable efficiency to erythrapheresis. In cases where erythrapheresis is not available, this method can be a good alternative for patients and care centers.

  3. Circulating Zonulin Correlates with Density of Enteroviruses and Tolerogenic Dendritic Cells in the Small Bowel Mucosa of Celiac Disease Patients.

    Science.gov (United States)

    Vorobjova, Tamara; Raikkerus, Helerin; Kadaja, Lumme; Talja, Ija; Uibo, Oivi; Heilman, Kaire; Uibo, Raivo

    2017-02-01

    Impaired intestinal integrity, including increased permeability of the small bowel mucosa, has been shown in patients with celiac disease (CD) as well as with type 1 diabetes (T1D). Zonulin (ZO, pre-haptoglobin), a tight junction regulator, plays a particular role in the regulation of intestinal barrier function and in the pathogenesis of the above-mentioned diseases. To investigate whether enteroviruses (EVs) and immunoregulatory cells are associated with intestinal permeability in patients with CD alone and with coexistent T1D. Altogether 80 patients (mean age 10.68 ± 6.69 years) who had undergone small bowel biopsy were studied. Forty patients with functional dyspepsia and normal small bowel mucosa formed the control group. The circulating ZO level in sera was evaluated using ELISA. The densities of EV, FOXP3+ regulatory T cells (Tregs), indoleamine 2,3-dioxygenase (IDO+) dendritic cells (DCs) and glutamic acid dexarboxylase (GAD)65+ cells in small bowel mucosa were investigated by immunohistochemistry. The expression analysis of FOXP3, tight junction protein 1 (TJP1), gap junction (GJA1), IDO and CD103 genes was evaluated by real-time PCR. The ZO level was higher in CD patients compared to subjects with a normal small bowel mucosa, particularly in those with Marsh IIIc atrophy (p = 0.01), and correlated with the density of EV (r = 0.63; p = 0.0003) and IDO+ DCs (r = 0.58; p = 0.01) in the small bowel mucosa. The density of GAD65+ epithelial cells was correlated with the density of EV (r = 0.59; p = 0.03) and IDO+ DCs (r = 0.78; p = 0.004) in CD patients. The relative expression of FOXP3 mRNA in the small bowel mucosa tissue was significantly higher in patients with CD, compared to subjects with a normal mucosa, and correlated with the density of EV (r = 0.62; p = 0.017) as well as with the relative expression of IDO mRNA (r = 0.54; p = 0.019). The CD is associated with elevation of the circulating ZO level, the value of which

  4. S1 nuclease analysis of α-globin gene expression in preleukemic patients with acquired hemoglobin H disease after transfer to mouse erythroleukemia cells

    International Nuclear Information System (INIS)

    Helder, J.; Deisseroth, A.

    1987-01-01

    The loss of α-globin gene transcriptional activity rarely occurs as an acquired abnormality during the evolution of myeloproliferative disease or preleukemia. To test whether the mutation responsible for the loss of α-globin gene expression (hemoglobin H disease) in these patients is linked with the α-globin genes on chromosome 16, the authors transferred chromosome 16 from preleukemic patients with acquired hemoglobin H disease to mouse erythroleukemia cells and measured the transcriptional activity of the human α-globin genes. After transfer to mouse erythroleukemia cells, the expression of human α-globin genes from the peripheral blood or marrow cells of preleukemic patients with acquired hemoglobin H disease was similar to that of human α-globin genes transferred to mouse erythroleukemia cells from normal donors. These data showed that factor(s) in the mouse erythroleukemia cell can genetically complement the α-globin gene defect in these preleukemia patients with acquired hemoglobin H disease and suggest that altered expression of a gene in trans to the α-globin gene may be responsible for the acquisition of hemoglobin H disease in these patients

  5. Characterization of Peripheral Immune Cell Subsets in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Peter Kraft

    2015-10-01

    Full Text Available Immune cells (IC play a crucial role in murine stroke pathophysiology. However, data are limited on the role of these cells in ischemic stroke in humans. We therefore aimed to characterize and compare peripheral IC subsets in patients with acute ischemic stroke/transient ischemic attack (AIS/TIA, chronic cerebrovascular disease (CCD and healthy volunteers (HV. We conducted a case-control study of patients with AIS/TIA (n = 116 or CCD (n = 117, and HV (n = 104 who were enrolled at the University Hospital Würzburg from 2010 to 2013. We determined the expression and quantity of IC subsets in the three study groups and performed correlation analyses with demographic and clinical parameters. The quantity of several IC subsets differed between the AIS/TIA, CCD, and HV groups. Several clinical and demographic variables independently predicted the quantity of IC subsets in patients with AIS/TIA. No significant changes in the quantity of IC subsets occurred within the first three days after AIS/TIA. Overall, these findings strengthen the evidence for a pathophysiologic role of IC in human ischemic stroke and the potential use of IC-based biomarkers for the prediction of stroke risk. A comprehensive description of IC kinetics is crucial to enable the design of targeted treatment strategies.

  6. Sickle Cell Disease (For Parents)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Sickle Cell Disease KidsHealth / For Parents / Sickle Cell Disease What's ... español Enfermedad de células falciformes What Is Sickle Cell Disease? Sickle cell disease is a condition in ...

  7. Cellular, pharmacological, and biophysical evaluation of explanted lungs from a patient with sickle cell disease and severe pulmonary arterial hypertension.

    Science.gov (United States)

    Rogers, Natasha M; Yao, Mingyi; Sembrat, John; George, M Patricia; Knupp, Heather; Ross, Mark; Sharifi-Sanjani, Maryam; Milosevic, Jadranka; St Croix, Claudette; Rajkumar, Revathi; Frid, Maria G; Hunter, Kendall S; Mazzaro, Luciano; Novelli, Enrico M; Stenmark, Kurt R; Gladwin, Mark T; Ahmad, Ferhaan; Champion, Hunter C; Isenberg, Jeffrey S

    2013-12-01

    Pulmonary hypertension is recognized as a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). We now report benchtop phenotyping from the explanted lungs of the first successful lung transplant in SCD. Pulmonary artery smooth muscle cells (PASMCs) cultured from the explanted lungs were analyzed for proliferate capacity, superoxide (O2 (•-)) production, and changes in key pulmonary arterial hypertension (PAH)-associated molecules and compared with non-PAH PASMCs. Upregulation of several pathologic processes persisted in culture in SCD lung PASMCs in spite of cell passage. SCD lung PASMCs showed growth factor- and serum-independent proliferation, upregulation of matrix genes, and increased O2 (•-) production compared with control cells. Histologic analysis of SCD-associated PAH arteries demonstrated increased and ectopically located extracellular matrix deposition and degradation of elastin fibers. Biomechanical analysis of these vessels confirmed increased arterial stiffening and loss of elasticity. Functional analysis of distal fifth-order pulmonary arteries from these lungs demonstrated increased vasoconstriction to an α1-adrenergic receptor agonist and concurrent loss of both endothelial-dependent and endothelial-independent vasodilation compared with normal pulmonary arteries. This is the first study to evaluate the molecular, cellular, functional, and mechanical changes in end-stage SCD-associated PAH.

  8. INCREASED VASOOCCLUSIVE CRISIS IN “O” BLOOD GROUP SICKLE CELL DISEASE PATIENTS: ASSOCIATION WITH UNDERLYING THROMBOSPONDIN LEVELS.

    Directory of Open Access Journals (Sweden)

    M. Al Huneini

    2017-04-01

    Full Text Available Abstract: Objectives: To explore the incidence of vaso-occlusive crisis (VOC in Blood Group “O” sickle cell disease (SCD patients, and correlate it with the blood group and thrombospondin (TSP levels. Methods: In 89 consecutive SCD patients, blood samples were obtained for vWF antigen, collagen binding activity, blood group typing, C-reactive protein, variant hemoglobin analysis (HPLC, Serum TSP 1 and TSP 2 levels, complete blood counts, liver function tests, LDH and renal function tests during VOC episodes and in steady state conditions. Results: In the steady state SCD patients (n=72, “O” blood group patients (n=37 showed significantly higher median serum TSP 1 and TSP 2 levels than the non “O” blood group patients [n=35] [p <0.05, Mann-Whitney test], with an inverse relation between VWF:Ag, Factor VIII:C and TSP levels. Furthermore, the serum TSP 1 and TSP 2 levels were significantly higher in patients presenting with acute VOC [n=17], and in those with repeated VOC’s (group 1, n=16 especially amongst those patients with blood group “O” [p, <0.05, Mann-Whitney test]. Conclusions: The study shows that there was an inverse relation between TSP and vWF levels, in blood group “O” SCD patients with an upregulation of the TSP levels. Expectedly, during active VOC crisis, the TSP 1 and TSP 2 levels were significantly elevated.    Key Words: VOC; SCD; TSP; vWD; Blood groups

  9. α-Synuclein Heterocomplexes with β-Amyloid Are Increased in Red Blood Cells of Parkinson’s Disease Patients and Correlate with Disease Severity

    Science.gov (United States)

    Daniele, Simona; Frosini, Daniela; Pietrobono, Deborah; Petrozzi, Lucia; Lo Gerfo, Annalisa; Baldacci, Filippo; Fusi, Jonathan; Giacomelli, Chiara; Siciliano, Gabriele; Trincavelli, Maria Letizia; Franzoni, Ferdinando; Ceravolo, Roberto; Martini, Claudia; Bonuccelli, Ubaldo

    2018-01-01

    Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1–42 (Aβ1–42) and tau, in both brain and peripheral tissues. In addition to oligomers, the role of the interactions of α-syn with Aβ or tau has gradually emerged. Nevertheless, despite intensive research, NDs have no accepted peripheral markers for biochemical diagnosis. In this respect, Red Blood Cells (RBCs) are emerging as a valid peripheral model for the study of aging-related pathologies. Herein, a small cohort (N = 28) of patients affected by Parkinson’s disease (PD) and age-matched controls were enrolled to detect the content of α-syn (total and oligomeric), Aβ1–42 and tau (total and phosphorylated) in RBCs. Moreover, the presence of α-syn association with tau and Aβ1–42 was explored by co-immunoprecipitation/western blotting in the same cells, and quantitatively confirmed by immunoenzymatic assays. For the first time, PD patients were demonstrated to exhibit α-syn heterocomplexes with Aβ1–42 and tau in peripheral tissues; interestingly, α-syn-Aβ1–42 concentrations were increased in PD subjects with respect to healthy controls (HC), and directly correlated with disease severity and motor deficits. Moreover, total-α-syn levels were decreased in PD subjects and inversely related to their motor deficits. Finally, an increase of oligomeric-α-syn and phosphorylated-tau was observed in RBCs of the enrolled patients. The combination of three parameters (total-α-syn, phosphorylated-tau and α-syn-Aβ1–42 concentrations) provided the best fitting predictive index for discriminating PD patients from controls. Nevertheless further investigations should be required, overall, these data suggest α-syn hetero-aggregates in RBCs as a putative tool for the diagnosis of PD. PMID:29520218

  10. A Mismatch Between Patient Education Materials About Sickle Cell Disease and the Literacy Level of Their Intended Audience.

    Science.gov (United States)

    McClure, Elizabeth; Ng, Jared; Vitzthum, Kelly; Rudd, Rima

    2016-05-12

    Despite the first goal of the 2010 National Action Plan to Improve Health Literacy, the literacy demands of much health information exceeds the reading skills of most US adults. The objective of this study was to assess the health literacy level of publicly available patient education materials for people with sickle cell disease (SCD). We used 5 validated tools to evaluate 9 print and 4 online patient education materials: the simple measure of gobbledygook (SMOG) to assess reading grade level, the Peter Mosenthal and Irwin Kirsch readability formula (PMOSE/IKIRSCH) to assess structure and density, the Patient Education Materials Assessment Tool (PEMAT) to assess actionability (how well readers will know what to do after reading the material) and understandability, the Centers for Disease Control and Prevention's (CDC's) Clear Communication Index (Index) to obtain a comprehensive literacy demand score, and the Printed Cancer Education Materials for African Americans Cultural Sensitivity Assessment Tool. Materials' scores reflected high reading levels ranging from 8th grade to 12th grade, appropriate (low) structural demand, and low actionability relative to understandability. CDC suggests that an appropriate Index score should fall in or above the 90th percentile. The scores yielded by materials evaluated in this assessment ranged from the 44th to the 76th percentiles. Eight of the 13 materials scored within the acceptable range for cultural sensitivity. Reading levels of available patient education materials exceed the documented average literacy level of the US adult population. Health literacy demands should be a key consideration in the revision and development of patient education materials for people with SCD.

  11. Distinctive genomic signature of neural and intestinal organoids from familial Parkinson's disease patient-derived induced pluripotent stem cells.

    Science.gov (United States)

    Son, M-Y; Sim, H; Son, Y S; Jung, K B; Lee, M-O; Oh, J-H; Chung, S-K; Jung, C-R; Kim, J

    2017-12-01

    The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic cause of Parkinson's disease (PD). There is compelling evidence that PD is not only a brain disease but also a gastrointestinal disorder; nonetheless, its pathogenesis remains unclear. We aimed to develop human neural and intestinal tissue models of PD patients harbouring an LRRK2 mutation to understand the link between LRRK2 and PD pathology by investigating the gene expression signature. We generated PD patient-specific induced pluripotent stem cells (iPSCs) carrying an LRRK2 G2019S mutation (LK2GS) and then differentiated into three-dimensional (3D) human neuroectodermal spheres (hNESs) and human intestinal organoids (hIOs). To unravel the gene and signalling networks associated with LK2GS, we analysed differentially expressed genes in the microarray data by functional clustering, gene ontology (GO) and pathway analyses. The expression profiles of LK2GS were distinct from those of wild-type controls in hNESs and hIOs. The most represented GO biological process in hNESs and hIOs was synaptic transmission, specifically synaptic vesicle trafficking, some defects of which are known to be related to PD. The results were further validated in four independent PD-specific hNESs and hIOs by microarray and qRT-PCR analysis. We provide the first evidence that LK2GS also causes significant changes in gene expression in the intestinal cells. These hNES and hIO models from the same genetic background of PD patients could be invaluable resources for understanding PD pathophysiology and for advancing the complexity of in vitro models with 3D expandable organoids. © 2017 British Neuropathological Society.

  12. Secondary Circulating Prostate Cells Predict Biochemical Failure in Prostate Cancer Patients after Radical Prostatectomy and without Evidence of Disease

    Directory of Open Access Journals (Sweden)

    Nigel P. Murray

    2013-01-01

    Full Text Available Introduction. Although 90% of prostate cancer is considered to be localized, 20%–30% of patients will experience biochemical failure (BF, defined as serum PSA >0.2 ng/mL, after radical prostatectomy (RP. The presence of circulating prostate cells (CPCs in men without evidence of BF may be useful to predict patients at risk for BF. We describe the frequency of CPCs detected after RP, relation with clinicopathological parameters, and association with biochemical failure. Methods and Patients. Serial blood samples were taken during followup after RP, mononuclear cells were obtained by differential gel centrifugation, and CPCs identified using standard immunocytochemistry using anti-PSA monoclonal antibodies. Age, pathological stage (organ confined, nonorgan confined, pathological grade, margin status (positive, negative, extracapsular extension, perineural, vascular, and lymphatic infiltration (positive, negative were compared with the presence/absence of CPCs and with and without biochemical failure. Kaplan Meier methods were used to compare the unadjusted biochemical failure free survival of patients with and without CPCs. Results. 114 men participated, and secondary CPCs were detected more frequently in patients with positive margins, extracapsular extension, and vascular and lymphatic infiltration and were associated with biochemical failure independent of these clinicopathological variables, and with a shorter time to BF. Conclusions. Secondary CPCs are an independent risk factor associated with increased BF in men with a PSA <0.2 ng/mL after radical prostatectomy, but do not determine if the recurrence is due to local or systemic disease. These results warrant larger studies to confirm the findings.

  13. Adult T-cell leukemia-associated antigen (ATLA) and anti-ATLA antibodies in patients with Hodgkin's disease in the Nagasaki District.

    Science.gov (United States)

    Kinoshita, K; Amagasaki, T; Yamada, Y; Ikeda, S; Momita, S; Toriya, K; Kamihira, S; Ichimaru, M

    1983-01-01

    Seven patients with Hodgkin's disease in the Nagasaki district were examined for adult T-cell leukemia-associated antigen (ATLA), a human retrovirus-associated antigen, and anti-ATLA antibodies. Anti-ATLA antibody reactivity with the ATLA-positive cultured cells from an ATL patient was demonstrated in four (57.1%) of seven patients. This suggests that infection by a human retrovirus may be closely associated with Hodgkin's disease in the Nagasaki district. However, ATLA could not be induced in the cultured mononuclear cells taken from biopsied lymph nodes of the three patients examined. Hence, it is necessary to collect more direct evidence in the search for a viral etiology of Hodgkin's disease.

  14. A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Wun Ted

    2013-02-01

    Full Text Available Abstract Background Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study. Methods The primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41 or placebo (n = 21 for 30 days. Platelet function by VerifyNow® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients. Results There were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events. Conclusions Despite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain.

  15. Molecular blood typing augments serologic testing and allows for enhanced matching of red blood cells for transfusion in patients with sickle cell disease.

    Science.gov (United States)

    Wilkinson, Katie; Harris, Samantha; Gaur, Prashant; Haile, Askale; Armour, Rosalind; Teramura, Gayle; Delaney, Meghan

    2012-02-01

    Sickle cell disease (SCD) patients have dissimilar red blood cell (RBC) phenotypes compared to the primarily Caucasian blood donor base due, in part, to underlying complex Rh and silenced Duffy expression. Gene array-based technology offers high-throughput antigen typing of blood donors and can identify patients with altered genotypes. The purpose of the study was to ascertain if RBC components drawn from predominantly Caucasian donors could provide highly antigen-matched products for molecularly typed SCD patients. SCD patients were genotyped by a molecular array (HEA Beadchip, BioArray Solutions). The extended antigen phenotype (C, c, E, e, K, k, Jk(a) , Jk(b) , Fy(a) , Fy(b) , S, s) was used to query the inventory using different matching algorithms; the resulting number of products was recorded. A mean of 96.2 RBC products was available for each patient at basic-level, 34 at mid-level, and 16.3 at high-level stringency. The number of negative antigens correlated negatively with the number of available products. The Duffy silencing mutation in the promoter region (67T>C) (GATA) was found in 96.5% of patients. Allowing Fy(b+) products for patients with GATA increased the number of available products by up to 180%, although it does not ensure prevention of Duffy antibodies in all patients. This feasibility study provides evidence that centers with primarily Caucasian donors may be able to provide highly antigen-matched products. Knowledge of the GATA status expands the inventory of antigen-matched products. Further work is needed to determine the most clinically appropriate match level for SCD patients. © 2012 American Association of Blood Banks.

  16. MANAGEMENT OF SICKLE CELL DISEASE

    Directory of Open Access Journals (Sweden)

    Rajesh

    2016-02-01

    Full Text Available Sickle cell disease (SCD is a genetically transmitted multisystem disease1 which includes a group of disorders that differs in severity sign and symptoms, The disease is not uniformly seen everywhere but it has some topographical distribution. In India, it is frequently seen in Central India, in and around the vicinity of Chhattisgarh in some religions in caste like kurmis, satnami, mahar, other backward caste and some tribes, it has great pathological significance considering the high morbidity and mortality resulting from the disease process. We have studied the cases of SCD from 2001 to 2015 series of such patients, since there is no cure of this disease, in regards to prevention of this genetic autosomal recessive disorder by marriage counseling, the incidence can be significantly reduced by avoiding consanguineous marriages in the susceptible community.

  17. Pregnancy outcome in patients with sickle cell disease in the UK--a national cohort study comparing sickle cell anaemia (HbSS) with HbSC disease.

    Science.gov (United States)

    Oteng-Ntim, Eugene; Ayensah, Benjamin; Knight, Marian; Howard, Jo

    2015-04-01

    We describe the findings from a national study of maternal and fetal outcomes of pregnancy in women with sickle cell disease (SCD). Data were collected via the United Kingdom Obstetric Surveillance System between 1 February 2010 and 31 January 2011 from 109 women, of whom 51 (46·8%) had HbSS and 44 (40·4%) had HbSC. Data included antenatal, maternal and fetal outcomes. Comparisons were made between women with HbSS and HbSC. Incidence of complications were acute pain (57%), blood transfusion (26%), urinary tract infection (UTI; 12%) and critical care unit admission (23%) and these were all more common in women with HbSS than HbSC. There was no difference in the incidence of acute chest syndrome, hypertension and venous thromboembolism between HbSS and HbSC. Women with HbSS were more likely to deliver at pregnancy. © 2014 John Wiley & Sons Ltd.

  18. Altered expression of signalling lymphocyte activation molecule receptors in T-cells from lupus nephritis patients-a potential biomarker of disease activity.

    Science.gov (United States)

    Stratigou, Victoria; Doyle, Anne F; Carlucci, Francesco; Stephens, Lauren; Foschi, Valentina; Castelli, Marco; McKenna, Nicola; Cook, H Terence; Lightstone, Liz; Cairns, Thomas D; Pickering, Matthew C; Botto, Marina

    2017-07-01

    The aim was to investigate whether the signalling lymphocyte activation molecule (SLAM) signalling pathways contribute to LN and whether SLAM receptors could be valuable biomarkers of disease activity. Peripheral blood mononuclear cells from 30National Research Ethics Service SLE patients with biopsy-proven LN were analysed by flow cytometry. Clinical measures of disease activity were assessed. The expression of the SLAM family receptors on T-cell subpopulations [CD4, CD8 and double negative (DN) T cells] was measured and compared between lupus patients with active renal disease and those in remission. The frequency of CD8 T cells expressing SLAMF3, SLAMF5 and SLAMF7 was significantly lower in LN patients who were in remission. In contrast, these subsets were similar in patients with active renal disease and in healthy individuals. Patients with active nephritis had an increased percentage of circulating monocytes, consistent with a potential role played by these cells in glomerular inflammation. Changes in the frequency of DN T cells positive for SLAMF2, SLAMF4 and SLAMF7 were observed in lupus patients irrespective of the disease activity. We detected alterations in the cellular expression of the SLAM family receptors, but these changes were less obvious and did not reveal any specific pattern. The percentage of DN T cells expressing SLAMF6 could predict the clinical response to B-cell depletion in patients with LN. Our study demonstrates altered expression of the SLAM family receptors in SLE T lymphocytes. This is consistent with the importance of the SLAM-associated pathways in lupus pathogenesis. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  19. Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease

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    Cheng-Jui Lin

    2016-12-01

    Full Text Available Background/Aims: Indoxyl sulfate (IS is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD. We explored the effect of IS on human early endothelial progenitor cells (EPCs and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. Methods: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD, pulse wave velocity (PWV, ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. Results: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS and free IS (F-IS were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR, hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. Conclusions: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.

  20. secretor status of sickle cell disease patients in Zaria, Kaduna State

    African Journals Online (AJOL)

    olayemitoyin

    Secretor enzyme) and to products that reside on ... associated with non ABH secretors are autoimmune diseases ... 1980., Kauffman et al, 1996), dental caries and abscess ... lung, liver, bone, skin, and kidneys (Hiran, 2005). ... reaction to occur.

  1. Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease

    International Nuclear Information System (INIS)

    Werner, Christian; Boehm, Michael; Friedrich, Erik B.

    2008-01-01

    Number and function of endothelial progenitor cells (EPCs) are down-regulated in patients with coronary artery disease (CAD). Integrin-linked kinase (ILK) is a signal and adaptor protein that regulates survival of mature endothelial cells and vascular development. Here we show that EPC dysfunction in patients with CAD is paralleled by down-regulation of ILK while restoration of ILK expression rescues the migratory defect of CAD-EPCs. Human EPCs transduced with dominant-negative ILK (DN-ILK) display significantly reduced expression of CD34 + /VEGFR-2 + , DiI-Ac-LDL uptake, and Ulex europaeus lectin binding. Mechanistically, DN-ILK-transfected EPCs are characterized by decreased proliferation, while proliferation is increased in wild-type ILK-transfected EPCs. These effects are paralleled by changes in cyclin D1 expression, colony forming units, and cytoskeletal rearrangement. Functionally, ILK is necessary and sufficient for SDF-1-triggered migration and adhesion in EPCs. These data extend current knowledge about the role of ILK in EPC biology and implicate ILK as a therapeutic target in CAD.

  2. Squamous Cell Carcinoma and Multiple Bowen's Disease in a Patient with a History of Consumption of Traditional Chinese Herbal Balls

    Directory of Open Access Journals (Sweden)

    Joon Seok

    2015-07-01

    Full Text Available Arsenic has been classified as a class I human carcinogen, meaning that there is sufficient evidence of carcinogenicity to humans. Arsenic, however, remains a common contaminant in a number of traditional Chinese herbal balls. A 64-year-old man presented with an erythematous erosive patch on the left palm, multiple yellowish scaly patches on the right palm and an erythematous hyperkeratotic patch with bleeding on the left foot dorsum. He also had similar skin lesions on the back and buttock. He had a past medical history of chronic exposure to arsenic through consumption of traditional Chinese herbal balls. Skin biopsy revealed Bowen's disease on the left palm and squamous cell carcinoma on left foot dorsum. We report this case to emphasize that we should investigate patient's history thoroughly, including the use of Chinese herbal balls to find out arsenicism.

  3. Therapeutic hemoglobin levels after gene transfer in β-thalassemia mice and in hematopoietic cells of β-thalassemia and sickle cells disease patients.

    Directory of Open Access Journals (Sweden)

    Laura Breda

    Full Text Available Preclinical and clinical studies demonstrate the feasibility of treating β-thalassemia and Sickle Cell Disease (SCD by lentiviral-mediated transfer of the human β-globin gene. However, previous studies have not addressed whether the ability of lentiviral vectors to increase hemoglobin synthesis might vary in different patients.We generated lentiviral vectors carrying the human β-globin gene with and without an ankyrin insulator and compared their ability to induce hemoglobin synthesis in vitro and in thalassemic mice. We found that insertion of an ankyrin insulator leads to higher, potentially therapeutic levels of human β-globin through a novel mechanism that links the rate of transcription of the transgenic β-globin mRNA during erythroid differentiation with polysomal binding and efficient translation, as reported here for the first time. We also established a preclinical assay to test the ability of this novel vector to synthesize adult hemoglobin in erythroid precursors and in CD34(+ cells isolated from patients affected by β-thalassemia and SCD. Among the thalassemic patients, we identified a subset of specimens in which hemoglobin production can be achieved using fewer copies of the vector integrated than in others. In SCD specimens the treatment with AnkT9W ameliorates erythropoiesis by increasing adult hemoglobin (Hb A and concurrently reducing the sickling tetramer (Hb S.Our results suggest two major findings. First, we discovered that for the purpose of expressing the β-globin gene the ankyrin element is particularly suitable. Second, our analysis of a large group of specimens from β-thalassemic and SCD patients indicates that clinical trials could benefit from a simple test to predict the relationship between the number of vector copies integrated and the total amount of hemoglobin produced in the erythroid cells of prospective patients. This approach would provide vital information to select the best candidates for these

  4. Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls.

    Science.gov (United States)

    Campbell, Claudia M; Carroll, C Patrick; Kiley, Kasey; Han, Dingfen; Haywood, Carlton; Lanzkron, Sophie; Swedberg, Lauren; Edwards, Robert R; Page, Gayle G; Haythornthwaite, Jennifer A

    2016-04-01

    Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity after laboratory-induced pain. We sought to examine this relationship in patients with SCD compared to healthy control participants. We completed quantitative sensory testing in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, body mass index, and education) to 27 healthy controls. Surprisingly, few quantitative sensory testing differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb, and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, whereas conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly because of tailoring the water temperature to a perceptual level; patients with SCD received milder temperatures. In the matched subsample, group differences and group-by-time interactions were observed in biomarkers including tumor necrosis factor alpha, interleukin-1ß, interleukin-4, and neuropeptide Y. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked proinflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in patients with SCD.

  5. Differential expression of NK receptors CD94 and NKG2A by T cells in rheumatoid arthritis patients in remission compared to active disease.

    Directory of Open Access Journals (Sweden)

    Ceara E Walsh

    Full Text Available TNF inhibitors (TNFi have revolutionised the treatment of rheumatoid arthritis (RA. Natural killer (NK cells and Natural Killer Cell Receptor+ T (NKT cells comprise important effector lymphocytes whose activity is tightly regulated through surface NK receptors (NKRs. Dysregulation of NKRs in patients with autoimmune diseases has been shown, however little is known regarding NKRs expression in patients with TNFi-induced remission and in those who maintain remission vs disease flare following TNFi withdrawal.Patients with RA were recruited for this study, (i RA patients in clinical remission following a minimum of one year of TNFi therapy (n = -15; (2 Active RA patients, not currently or ever receiving TNFi (n = 18; and healthy control volunteers (n = 15. Patients in remission were divided into two groups: those who were maintained on TNFi and those who withdrew from TNFi and maintained on DMARDS. All patients underwent full clinical assessment. Peripheral blood mononuclear cells were isolated and NKR (CD94, NKG2A, CD161, CD69, CD57, CD158a, CD158b expression on T-(CD3+CD56-, NK-(CD3-CD56+ and NKT-(CD3+CD56+ cells was determined by flow cytometry.Following TNFi withdrawal, percentages and numbers of circulating T cells, NK cells or NKT cell populations were unchanged in patients in remission versus active RA or HCs. Expression of the NKRs CD161, CD57, CD94 and NKG2A was significantly increased on CD3+CD56-T cells from patients in remission compared to active RA (p<0.05. CD3+CD56-T cell expression of CD94 and NKG2A was significantly increased in patients who remained in remission compared with patients whose disease flared (p<0.05, with no differences observed for CD161 and CD57. CD3+CD56- cell expression of NKG2A was inversely related to DAS28 (r = -0.612, p<0.005.High CD94/NKG2A expression by T cells was demonstrated in remission patients following TNFi therapy compared to active RA, while low CD94/NKG2A were associated with

  6. Characterization of pituitary cells targeted by antipituitary antibodies in patients with isolated autoimmune diseases without pituitary insufficiency may help to foresee the kind of future hypopituitarism.

    Science.gov (United States)

    De Bellis, A; Dello Iacovo, A; Bellastella, G; Savoia, A; Cozzolino, D; Sinisi, A A; Bizzarro, A; Bellastella, A; Giugliano, D

    2014-10-01

    Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism. Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up. Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism. The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy.

  7. Calcified pulmonary thromboembolism in a child with sickle cell disease: value of multidetector CT in patients with acute chest syndrome

    International Nuclear Information System (INIS)

    Staser, Jonathan A.; Alam, Tariq; Applegate, Kimberly

    2006-01-01

    The incidence of pulmonary embolism in children is not clearly known, but is believed to be low. Risk factors for pulmonary thromboembolism include central venous catheter, malignancy, surgery, infection, trauma, and congenital hypercoagulable disorders. Children with sickle cell disease are prothrombotic and are at an increased risk of thromboembolism. The incidence of this event is unknown because these children are often not thoroughly imaged. We report here a case of a calcified pulmonary thromboembolism in a child with sickle cell disease and emphasize the use of multidetector CT in detection of pulmonary thromboembolism in children with sickle cell disease. (orig.)

  8. Association between red cell distribution width and the risk of heart events in patients with coronary artery disease.

    Science.gov (United States)

    Li, Weimin; Li, Xiaoting; Wang, Maofeng; Ge, Xuan; Li, Feixiang; Huang, Bian; Peng, Jiren; Li, Guohong; Lu, Liang; Yu, Zhuoyuan; Ma, Jiaojiao; Xu, Liaohang; Jin, Meijuan; Si, Hongping; Wan, Rugen

    2015-04-01

    Red cell distribution width (RDW) has been found to be a novel prognostic biomarker in patients with coronary artery disease (CAD); however, the association between RDW and the risk of heart events in patients with CAD is yet to be fully elucidated. Thus, the aim of the present study was to determine whether an elevated RDW was associated with the Framingham risk score (FRS) in patients with CAD. Data were retrospectively collected from Affiliated Dongyang Hospital of Wenzhou Medical University (Dongyang, China). The patients had undergone a coronary angiography and their clinical data were integrated. The patients (male, 260; female, 132) were divided into two groups based on the results of the coronary angiography, namely the CAD (n=283) and control groups (n=109). The FRS was calculated for all the subjects, and complete blood count testing with biochemical measurements was performed. The mean RDW level was 13.7±1.8% in the CAD group and 13.1±1.0% in the control group, while the mean FRS was 9.0±4.9 in the CAD group and 6.4±3.9 in the control group. The RDW and FRS were significantly higher in the CAD group compared with the control group (P0.05). The RDW was shown to significantly correlate with the red blood cell (RBC) count ( r =-0.133, P=0.029), hemoglobin level ( r =-0.207, P=0.001) and TG level ( r =0.226, P<0.001) within the laboratory parameters, as well as the FRS ( r =0.206, P<0.001). In the stepwise multivariate linear regression, which included the RBC count, hemoglobin level, TG level and RDW, the FRS was predicted by hemoglobin ( r 2 =0.034, P=0.001), TG ( r 2 =0.059, P<0.001) and RDW ( r 2 =0.030, P=0.003) parameters. Therefore, a novel association was revealed between higher levels of RDW and an elevated FRS in patients with CAD, which raises the possibility that a simple marker, RDW, may be associated with an increased risk of heart events in CAD patients.

  9. IL-32 expression in the airway epithelial cells of patients with Mycobacterium avium complex lung disease.

    NARCIS (Netherlands)

    Bai, X.; Ovrutsky, A.R.; Kartalija, M.; Chmura, K.; Kamali, A.; Honda, J.R.; Oberley-Deegan, R.E.; Dinarello, C.A.; Crapo, J.D.; Chang, L.Y.; Chan, E.D.

    2011-01-01

    Lung disease due to Mycobacterium avium complex (MAC) organisms is increasing. A greater understanding of the host immune response to MAC organisms will provide a foundation to develop novel therapies for these recalcitrant infections. IL-32 is a newly described pro-inflammatory cytokine that

  10. Analysis of correlations between selected endothelial cell activation markers, disease activity, and nailfold capillaroscopy microvascular changes in systemic lupus erythematosus patients.

    Science.gov (United States)

    Ciołkiewicz, Mariusz; Kuryliszyn-Moskal, Anna; Klimiuk, Piotr Adrian

    2010-02-01

    The aim of the study was to evaluate the correlation between selected serum endothelial cell activation markers such as vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble thrombomodulin (sTM), soluble E-selectin (sE-selectin), disease activity, and microvascular changes determined by nailfold capillaroscopy in patients with systemic lupus erythematosus (SLE). Serum levels of VEGF, ET-1, sTM, and sE-selectin were determined by an enzyme-linked immunosorbent assay in 80 SLE patients. The disease activity was measured with Systemic Lupus Erythematosus Disease Activity Index score. Nailfold capillaroscopy was performed in all patients. Positive correlation was found between VEGF and both ET-1 (r = 0.294, p nailfold capillaroscopy (r = 0.458, p nailfold capillaroscopy. The relationship between changes in nailfold capillaroscopy, endothelial cell activation markers, and the clinical activity of SLE points to an important role of microvascular abnormalities in the clinical manifestation of the disease.

  11. Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Yasufumi Masaki

    2012-01-01

    Full Text Available IgG4-related disease is a new disease classification established in Japan in the 21st century. Patients with IgG4-related disease display hyper-IgG4-gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and good response to glucocorticoids. Since IgG4 overexpression is also observed in other disorders, it is necessary to diagnose IgG4-related disease carefully and correctly. We therefore sought to determine cutoff values for serum IgG4 and IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related disease. Patients and Methods. We retrospectively analyzed serum IgG4 concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of 132 patients with IgG4-related disease and 48 patients with other disorders. Result. Serum IgG4 >135  mg/dl demonstrated a sensitivity of 97.0% and a specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively. IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of 94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in severely fibrotic parts of tissues. Conclusion. Although a recent unanimous consensus of all relevant researchers in Japan recently established the diagnostic criteria for IgG4-related disease, findings such as ours indicate that further discussion is needed.

  12. Human T-cell responses to Aspergillus fumigatus : In healthy individuals and patients with Aspergillus-related disease

    NARCIS (Netherlands)

    Jolink, H.

    2017-01-01

    The T-cell mediated immune response to Aspergillus fumigatus was studied in healthy individuals and in several patient groups. In peripheral blood of healthy individuals low frequencies of Aspergillus-specific CD4+ T-cells with a Thelper 1 profile were present. In patients with invasive

  13. Precision of SPECT/CT allows the diagnosis of a hidden Brodie's abscess of the talus in a patient with sickle cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Al jafar, Hassan [Dept. of Hematology, Amiri Hospital, Kuwait (Kuwait); Al Shemmeri, Eman [Dept. of Nuclear Medicine, Farwaniya Hospital, Al-Farwania (Kuwait); Al Shemmeri, Jehan; Al Enizi, Saud [Faculty of Medicine, Nuclear Medicine Dept, Kuwait University, Kuwait (Kuwait); Aytglu, Leena [Molecular Imaging Center, Jaber Al-Ahmad Center, Kuwait (Kuwait); Afzai, Uzma [Dept. of Nuclear Medicine, Farwaniya Hospital, Al-Farwania (Kuwait)

    2015-06-15

    Brodie's abscess is a rare subacute osteomyelitis that can be found in sickle cell disease along with other bone complications. A 21-year-old female with sickle cell disease was presenting frequently to the medical casualty department for painful vasoocclusive crises and for persistent ankle pain and swelling. Hybrid imaging with single-photon emission computed tomography-computed tomography (SPECT-CT) incidentally revealed Brodie's abscess in the talus bone of the ankle, causing persisting long-standing pain. SPECT-CT is a modern technology used to scan bone to detect both anatomical and functional abnormalities with high specificity. Brodie's abscess is a rare bone inflammation that could be a hidden cause of pain and infection in sickle cell disease. Although rare, this lesion requires more attention in patients with sickle cell disease because their immunocompromised status renders them prone to this infection.

  14. Precision of SPECT/CT allows the diagnosis of a hidden Brodie's abscess of the talus in a patient with sickle cell disease

    International Nuclear Information System (INIS)

    Al jafar, Hassan; Al Shemmeri, Eman; Al Shemmeri, Jehan; Al Enizi, Saud; Aytglu, Leena; Afzai, Uzma

    2015-01-01

    Brodie's abscess is a rare subacute osteomyelitis that can be found in sickle cell disease along with other bone complications. A 21-year-old female with sickle cell disease was presenting frequently to the medical casualty department for painful vasoocclusive crises and for persistent ankle pain and swelling. Hybrid imaging with single-photon emission computed tomography-computed tomography (SPECT-CT) incidentally revealed Brodie's abscess in the talus bone of the ankle, causing persisting long-standing pain. SPECT-CT is a modern technology used to scan bone to detect both anatomical and functional abnormalities with high specificity. Brodie's abscess is a rare bone inflammation that could be a hidden cause of pain and infection in sickle cell disease. Although rare, this lesion requires more attention in patients with sickle cell disease because their immunocompromised status renders them prone to this infection

  15. Epstein-Barr virus (EBV) load in cerebrospinal fluid and peripheral blood of patients with EBV-associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Liu, Q-F; Ling, Y-W; Fan, Z-P; Jiang, Q-L; Sun, J; Wu, X-L; Zhao, J; Wei, Q; Zhang, Y; Yu, G-P; Wu, M-Q; Feng, R

    2013-08-01

    To evaluate the diagnostic and prognostic utility of monitoring the Epstein-Barr virus (EBV) load in the cerebrospinal fluid (CSF) and peripheral blood for the patients with EBV-associated central nervous system (CNS) diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT), 172 patients undergoing allo-HSCT were enrolled in the study. The EBV DNA levels of blood were monitored regularly in recipients of transplants for 3 years post transplantation. The EBV DNA levels of CSF were monitored in patients with EBV-associated CNS diseases before the treatment and at different points following the treatment. Post-transplant EBV-associated diseases developed in 27 patients, including 12 patients with EBV-associated CNS diseases. The 3-year cumulative incidences of EBV-associated diseases and EBV-associated CNS diseases were 19.5 ± 3.5% and 8.6 ± 2.4%, respectively. Patients with EBV-associated diseases showed higher loads of EBV DNA in their blood compared with patients with EBV DNA-emia. No difference was seen between the EBV DNA levels of blood in patients with CNS involvement and patients without CNS involvement. The EBV DNA loads of blood increased 3-14 days before the clinical manifestations of EBV-associated diseases emerged. The EBV DNA loads of CSF were higher than that of blood in patients with EBV-associated CNS diseases. In 12 patients with EBV-associated CNS diseases, EBV DNA levels were declining in both blood and CSF with the control of diseases, and the EBV DNA loads of CSF decreased faster than that of blood in 5 patients who responded to treatment, and the EBV DNA levels of CSF increased in 5 patients who were unresponsive to treatment. On multivariate analysis, the use of anti-thymocyte globulin and intensified conditioning regimens were independent risk factors for EBV-associated diseases and EBV-associated CNS diseases. EBV-associated CNS diseases are not rare after allo-HSCT. The EBV DNA loads of CSF could act as an important

  16. Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease.

    Science.gov (United States)

    Chun, Yong Soon; Chaudhari, Pooja; Jang, Yoon-Young

    2010-12-14

    The recent advances in the induced pluripotent stem cell (iPSC) research have significantly changed our perspectives on regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. In this review, we describe the human iPSC generation from developmentally diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human iPSCs) and multistage hepatic differentiation protocols, and discuss both basic and clinical applications of these cells including disease modeling, drug toxicity screening/drug discovery, gene therapy and cell replacement therapy.

  17. Hydroxyurea therapy in adult Nigerian sickle cell disease: a monocentric survey on pattern of use, clinical effects and patient's compliance.

    Science.gov (United States)

    Adewoyin, Ademola Samson; Oghuvwu, Omokiniovo Sunday; Awodu, Omolade Augustina

    2017-03-01

    The clinical prospects of hydroxyurea therapy in the management of sickle cell disease (SCD) require evaluation in the Nigerian setting to develop indigenous guidelines. This survey examines the pattern of hydroxyurea therapy, its clinico-haematologic benefits and safety profile in Nigerian SCD subjects. A cross sectional pilot survey was carried out among 60 adult SCD subjects over 3 months. Data on clinical phenotypes, relevant haematological parameters and details of hydroxyurea therapy were obtained using a structured questionnaire through an interview process and case file review. The median age was 30 years. Thirty-four (56.7%) of the subjects are aware of hydroxyurea therapy in SCD. Twenty-four (40%) SCD patients had previously used hydroxyurea. Only 4 subjects were fully compliant. Reasons for non-compliance included poor knowledge and lack of funds. In particular, hydroxyurea reduced leucocyte count and increased mean red cell volume (MCV) in compliant subjects. Hydroxyurea use is low among Nigerian SCD subjects despite its proven efficacy/clinical prospects in the developed nations. Large scale multicenter studies and clinical trials are needed to form a basis for developing standard local treatment protocol for its use.

  18. Clinical utility of neuronal cells directly converted from fibroblasts of patients for neuropsychiatric disorders: studies of lysosomal storage diseases and channelopathy

    Science.gov (United States)

    Kano, Shin-ichi; Yuan, Ming; Cardarelli, Ross A.; Maegawa, Gustavo; Higurashi, Norimichi; Gaval-Cruz, Meriem; Wilson, Ashley M.; Tristan, Carlos; Kondo, Mari A.; Chen, Yian; Koga, Minori; Obie, Cassandra; Ishizuka, Koko; Seshadri, Saurav; Srivastava, Rupali; Kato, Takahiro A.; Horiuchi, Yasue; Sedlak, Thomas W.; Lee, Yohan; Rapoport, Judith L.; Hirose, Shinichi; Okano, Hideyuki; Valle, David; O'Donnell, Patricio; Sawa, Akira; Kai, Mihoko

    2015-01-01

    Methodologies for generating functional neuronal cells directly from human fibroblasts [induced neuronal (iN) cells] have been recently developed, but the research so far has only focused on technical refinements or recapitulation of known pathological phenotypes. A critical question is whether this novel technology will contribute to elucidation of novel disease mechanisms or evaluation of therapeutic strategies. Here we have addressed this question by studying Tay-Sachs disease, a representative lysosomal storage disease, and Dravet syndrome, a form of severe myoclonic epilepsy in infancy, using human iN cells with feature of immature postmitotic glutamatergic neuronal cells. In Tay-Sachs disease, we have successfully characterized canonical neuronal pathology, massive accumulation of GM2 ganglioside, and demonstrated the suitability of this novel cell culture for future drug screening. In Dravet syndrome, we have identified a novel functional phenotype that was not suggested by studies of classical mouse models and human autopsied brains. Taken together, the present study demonstrates that human iN cells are useful for translational neuroscience research to explore novel disease mechanisms and evaluate therapeutic compounds. In the future, research using human iN cells with well-characterized genomic landscape can be integrated into multidisciplinary patient-oriented research on neuropsychiatric disorders to address novel disease mechanisms and evaluate therapeutic strategies. PMID:25732146

  19. Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom.

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    Mark T Gladwin

    Full Text Available The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD is controversial.We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV≥ 3.0 m/s cuttof, which has a 67-75% positive predictive value for mean pulmonary artery pressure ≥ 25 mm Hg was used. Among 572 subjects, 11.2% had TRV ≥ 3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥ 160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV ≥ 3.0 m/sec. At 24 months the cumulative survival was 83% with TRV ≥ 3.0 m/sec and 98% with TRV 47 years, male gender, chronic transfusions, WHO class III-IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death.A TRV ≥ 3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable. The study is registered in ClinicalTrials.gov with identifier: NCT00492531.

  20. Standardization method for measurement of hydroxyurea by Ultra High Efficiency Liquid Chromatography in plasma of patients with sickle cell disease

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    Darcielle Bruna Dias Elias

    2014-09-01

    Full Text Available Sickle cell anemia (SCA is a recessively inherited disease characterized by chronic hemolytic anemia, chronic inflammation, and acute episodes of hemolysis. Hydroxyurea (HU is widely used to increase the levels of fetal hemoglobin (HbF. The objective of this study was to standardize and validate a method for the quantification of HU in human plasma by using ultra high performance liquid chromatography (UPLC in order to determine the plasma HU levels in adult patients with SCA who had been treated with HU. We used an analytical reverse phase column (Nucleosil C18 with a mobile phase consisting of acetonitrile/water (16.7/83.3. The retention times of HU, urea, and methylurea were 6.7, 7.7, and 11.4 min, respectively. All parameters of the validation process were defined. To determine the precision and accuracy of quality controls, HU in plasma was used at concentrations of 100, 740, and 1600 µM, with methylurea as the internal standard. Linearity was assessed in the range of 50-1600 µM HU in plasma, obtaining a correlation coefficient of 0.99. The method was accurate and precise and can be used for the quantitative determination of HU for therapeutic monitoring of patients with SCA treated with HU.

  1. Radiotherapy in patients with connective tissue diseases.

    Science.gov (United States)

    Giaj-Levra, Niccolò; Sciascia, Savino; Fiorentino, Alba; Fersino, Sergio; Mazzola, Rosario; Ricchetti, Francesco; Roccatello, Dario; Alongi, Filippo

    2016-03-01

    The decision to offer radiotherapy in patients with connective tissue diseases continues to be challenging. Radiotherapy might trigger the onset of connective tissue diseases by increasing the expression of self-antigens, diminishing regulatory T-cell activity, and activating effectors of innate immunity (dendritic cells) through Toll-like receptor-dependent mechanisms, all of which could potentially lead to breaks of immune tolerance. This potential risk has raised some debate among radiation oncologists about whether patients with connective tissue diseases can tolerate radiation as well as people without connective tissue diseases. Because the number of patients with cancer and connective tissue diseases needing radiotherapy will probably increase due to improvements in medical treatment and longer life expectancy, the issue of interactions between radiotherapy and connective tissue diseases needs to be clearer. In this Review, we discuss available data and evidence for patients with connective tissue diseases treated with radiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Prognostic role of patient gender in limited-disease small-cell lung cancer treated with chemoradiotherapy

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    Roengvoraphoj, Olarn; Eze, Chukwuka; Niyazi, Maximilian; Li, Minglun; Belka, Claus; Manapov, Farkhad [LMU Munich, Department of Radiation Oncology, Munich (Germany); Hildebrandt, Guido [University of Rostock, Department of Radiation Oncology, Rostock (Germany); Fietkau, Rainer [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany)

    2017-02-15

    Previous studies have demonstrated that female gender could be a prognostic factor in limited-disease (LD) small-cell lung cancer (SCLC), but the correlation between patient gender and survival parameters remains unclear. Data from 179 LD SCLC patients treated with definitive chemoradiotherapy (CRT) were reviewed. Influence of patient gender on time to progression (TTP), local control (LC), brain metastasis-free (BMFS), distant metastasis-free (DMFS) and overall survival (OS) was analysed. Definitive CRT was completed by 179 (110 men/69 women) patients. Of these, 68 (38%; 34 men/34 women) patients were treated in concurrent and 111 (62%; 76 men/35 women) in sequential mode. Prophylactic cranial irradiation (PCI) was subsequently applied in 70 (39%; 36 men/34 women) patients with partial or complete response after CRT. Median OS was 20 (95% confidence interval [CI] 10-22) and 14 (95% CI 10-18) months in female and male patients, respectively (p = 0.021). In subgroups defined by remission status (complete and partial response) after CRT, an OS benefit for females compared to males was also detected. There was no correlation between patient gender and TTP, LC or DMFS, and no difference in OS in the female and male subgroups treated with PCI. The incidence of metachronous brain metastases (BMs) in the male and female subgroups differed significantly (40/110 men vs. 18/69 women, p = 0.03). Also, mean BMFS was significantly longer in women (p = 0.023). Patient gender also significantly correlated with OS on multivariate analysis after adjustment for other prognostic factors (p = 0.04, HR 1.38, 95% CI 1.08-1.92). In this heterogeneous LD SCLC patient cohort treated with definitive CRT, female gender was significantly associated with longer BMFS and OS, as well as with a lower incidence of metachronous brain failure. (orig.) [German] Studien haben gezeigt, dass weibliches Geschlecht ein prognostischer Faktor beim kleinzelligen Lungenkarzinom (SCLC) im Stadium &apos

  3. Sickle cell disease and pregnancy: analysis of 34 patients followed at the Regional Blood Center of Ribeirão Preto, Brazil

    Directory of Open Access Journals (Sweden)

    Ana Cristina Silva-Pinto

    2014-10-01

    Full Text Available Objective: The objective of this study was to verify the evolution of pregnancies in sickle cell patients followed at one institution over a period of 12 years (January 2000 to June 2012. Methods: The study evaluated 34 pregnant women with sickle cell disease with a mean age of 23.9 ± 5.3 years. The incidence of obstetric complications, non-obstetric complications linked to sickle cell disease and complications in the newborn were analyzed. Results: A total of 26% of the cases reported previous miscarriages, 20% had preterm labor, 10% had pre-eclampsia, and 5% had gestational diabetes. Forty-one percent of the deliveries were cesarean sections and 29% of patients required blood transfusions. In respect to sickle cell disease, 62% of patients had vaso-occlusive crises, 29% had acute chest syndrome, 23% had urinary tract infection, 15% had impaired cardiac function and 6% developed pulmonary hypertension. Only one patient died in the postnatal period due to acute chest syndrome. The mean gestational age was 37.8 ± 2.63 weeks, and mean newborn weight was 2.809 ± 643.8 g. There were seven fetal losses, including three stillbirths and four miscarriages. The impact of transfusion therapy on the incidence of maternal–fetal complications during pregnancy was evaluated. Conclusions: Pregnancy in sickle cell patients is still associated with complications. Although no statistical difference was observed between transfused and non-transfused women, there were no deaths (fetal or maternal in transfused patients whereas one maternal death and three stillbirths occurred in non-transfused women. A larger study of sickle cell pregnant women will be necessary to elucidate the actual role of transfusion during pregnancy in sickle cell disease.

  4. Renal disease in patients with celiac disease.

    Science.gov (United States)

    Boonpheng, Boonphiphop; Cheungpasitporn, Wisit; Wijarnpreecha, Karn

    2018-04-01

    Celiac disease, an inflammatory disease of small bowel caused by sensitivity to dietary gluten and related protein, affects approximately 0.5-1% of the population in the Western world. Extra-intestinal symptoms and associated diseases are increasingly recognized including diabetes mellitus type 1, thyroid disease, dermatitis herpetiformis and ataxia. There have also been a number of reports of various types of renal involvement in patients with celiac disease including diabetes nephropathy, IgA nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, nephrotic syndrome related to malabsorption, oxalate nephropathy, and associations of celiac disease with chronic kidney disease and end-stage kidney disease. This review aims to present the current literature on possible pathologic mechanisms underlying renal disease in patients with celiac disease.

  5. [Immunology in the medical practice.XXXII. Transplantation of autologous hematopoietic stem cells for treatment of refractory auto-immune diseases; preliminary favorable results with 35 patients].

    Science.gov (United States)

    Vlieger, A M; van den Hoogen, F H; Brinkman, D M; van Laar, J M; Schipperus, M; Kruize, A A; Wulffraat, N M

    2000-08-12

    The objective of this study was to document the experiences in the first Dutch pilot studies of the effect of transplantation of autologous haematopoietic stem cells in patients with therapy-resistant autoimmune disease. The first results in 21 adults and 14 children are promising: remission of the disease was achieved in 13 patients, while in the others a significant reduction of disease activity was seen with a corresponding improvement of the quality of life. Infectious complications were frequently observed. Two children with systemic juvenile idiopathic arthritis developed a fatal infection-associated macrophage activation syndrome. Multicentre randomised studies are necessary to study the effects of autologous stem cell transplantation and modifications such as T-cell depletion.

  6. DNA-repair and mutations in immuncompetent cells from patients with rheumatic diseases and corresponding animal models

    International Nuclear Information System (INIS)

    Altmann, H.

    1977-01-01

    Unscheduled DNA synthesis was investigated in lymphocytes of patients with different inflammatory rheumatic diseases. After γ-irradiation H 3 -thymidin incorporation in DNA and DNA rejoining was reduced. After UV-irradiation the first step (90 min) of unscheduled DNA synthesis was above the controls. Some animal models for human diseases showed the same trend. An infectious ethiology was discussed for some of these diseases. (author)

  7. Eliminating Hairy Cell Leukemia Minimal Residual Disease

    Science.gov (United States)

    In this trial, patients with hairy cell leukemia who have disease-related symptoms that require treatment will be randomly assigned to receive cladribine with either concurrent rituximab or rituximab at least 6 months after completing cladribine therapy.

  8. Effect of Hereditary Hemochromatosis Gene H63D and C282Y Mutations on Iron Overload in Sickle Cell Disease Patients

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    Yunus Kasım Terzi

    2016-12-01

    Full Text Available Objective: Hemochromatosis is an autosomal recessive disease that is one of the most important reasons for iron overload. Sickle cell disease is a hemoglobinopathy that occurs as a result of a homozygous mutation in the hemoglobin gene. Erythrocyte transfusion is frequently used in the treatment of this disease. Iron overload as a result of transfusion is important in the mortality and morbidity of sickle cell anemia patients as well as in other hemoglobinopathies. In this study, the effect of hemochromatosis gene (HFE p.H63D and p.C282Y mutations on transfusion-related cardiac and liver iron overload in sickle cell disease patients who carry homozygous hemoglobin S mutation has been investigated. Materials and Methods: This is a prospective single-center crosssectional study in patients with homozygous hemoglobin S mutation between the years 2008 and 2013. The patients were divided into two groups. The first group (group A, n=31 was receiving chelation therapy and the second group (group B, n=13 was not. Direct and indirect iron loads were analyzed by magnetic resonance imaging and biochemically, respectively. HFE gene mutations were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analyses were performed by independent samples t-test. Results: p.H63D mutation was detected in 10 (32.3% patients in group A and in only 1 patient (7.7% in group B. When the 2 groups were compared for iron overload, iron deposition in the liver was significantly higher in group B (p=0.046. In addition, in group A, iron deposition was significantly higher in HFE mutation carriers compared to patients without the mutation (p=0.05. Conclusion: Results of this study showed that HFE gene mutations are important in iron deposition in the liver in patients with sickle cell disease.

  9. Low Rate of Detection of Mucosal High-Risk-Type Human Papillomavirus in Korean Patients with Extragenital Bowen's Disease and Squamous Cell Carcinoma, Especially in Digital Cases

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    Hye-Rim Park

    2013-01-01

    Full Text Available Human papillomavirus (HPV infection has been demonstrated in some of the nonmelanoma skin cancers as well as in precancerous lesions. Multiple infections of mucosal high-risk HPV may contribute to the onset of digital Bowen's disease through, if any, digital-genital transmission. We screened for the presence of the mucosal HPV DNA in patients with extragenital Bowen's disease (, squamous cell carcinoma (, bowenoid papulosis (, verrucous carcinoma (, actinic keratosis (, and basal cell carcinoma (. We used a PANArray HPV Genotyping Chip for high-risk and low-risk mucosal types. Genotyping data was confirmed using a conventional direct DNA sequencing method. Two cases of extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. None of the squamous cell carcinoma cases were positive. Neither patients with digital Bowen's disease ( nor those with squamous cell carcinoma ( showed any mucosal high-risk HPV. Mucosal high-risk HPV DNA was confirmed in 5 (55.6% of the 9 patients with bowenoid papulosis. HPV 16 was most prevalent (, while the DNA of HPVs 35 and 67 was detected in one sample for each of the two types. Our study demonstrated that two (6.7% of the patients with 30 extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV, respectively. HPVs belonging to the mucosal high-risk group may participate in the development of extragenital Bowen's disease. However, we could not find any relationship between the mucosal high-risk HPV and Bowen's disease or squamous cell carcinoma in the fingers.

  10. SUPPLEMENTATION OF PATIENTS WITH HOMOZYGOUS SICKLE-CELL DISEASE WITH ZINC, ALPHA-TOCOPHEROL, VITAMIN-C, SOYBEAN OIL, AND FISH OIL

    NARCIS (Netherlands)

    MUSKIET, FAJ; MUSKIET, FD; MEIBORG, G; SCHERMER, JG

    1991-01-01

    Thirteen patients (aged 0.7-17.9 y) with homozygous sickle cell disease were supplemented with alpha-tocopherol, vitamin C, zinc, and soybean oil (suppl 1; for 8 mo) and alpha-tocopherol, vitamin C, and fish oil (suppl 2; for 7 mo). Urinary zinc (suppl 1), plasma vitamin C, plasma cholesterol ester

  11. Varied autopsy findings in five treated patients with Gaucher disease and parkinsonism include the absence of Gaucher cells.

    Science.gov (United States)

    Monestime, Gianina; Borger, Daniel K; Kim, Jenny; Lopez, Grisel; Allgaeuer, Michael; Jain, Dhanpat; Vortmeyer, Alexander; Wang, Hao-Wei; Sidransky, Ellen

    2016-05-01

    Enzyme replacement therapy is standard of care for patients with Gaucher disease, as it significantly improves skeletal, visceral, and hematological symptoms. Few pathological studies have documented the extent of pathological findings in treated patients. Autopsy findings in five treated patients, who ultimately developed parkinsonism, ranged from the complete absence of Gaucher pathology to extensive involvement of multiple tissues, without correlation to age, genotype, spleen status, or dose/duration of therapy. Additional autopsies may elucidate modifiers and biomarkers contributing to disease burden and response to therapy. Published by Elsevier Inc.

  12. Expression of Foxp3 in colorectal cancer but not in Treg cells correlates with disease progression in patients with colorectal cancer.

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    Mia Kim

    Full Text Available BACKGROUND: Regulatory T cells (Treg expressing the transcription factor forkhead-box protein P3 (Foxp3 have been identified to counteract anti-tumor immune responses during tumor progression. Besides, Foxp3 presentation by cancer cells itself may also allow them to evade from effector T-cell responses, resulting in a survival benefit of the tumor. For colorectal cancer (CRC the clinical relevance of Foxp3 has not been evaluated in detail. Therefore the aim of this study was to study its impact in colorectal cancer (CRC. METHODS AND FINDINGS: Gene and protein analysis of tumor tissues from patients with CRC was performed to quantify the expression of Foxp3 in tumor infiltrating Treg and colon cancer cells. The results were correlated with clinicopathological parameters and patients overall survival. Serial morphological analysis demonstrated Foxp3 to be expressed in cancer cells. High Foxp3 expression of the cancer cells was associated with poor prognosis compared to patients with low Foxp3 expression. In contrast, low and high Foxp3 level in tumor infiltrating Treg cells demonstrated no significant differences in overall patient survival. CONCLUSIONS: Our findings strongly suggest that Foxp3 expression mediated by cancer cells rather than by Treg cells contribute to disease progression.

  13. Application of Fourier transform infrared spectroscopy to biomolecular profiling of cultured fibroblast cells from Gaucher disease patients: A preliminary investigation.

    Science.gov (United States)

    Igci, Nasit; Sharafi, Parisa; Demiralp, Duygu Ozel; Demiralp, Cemil Ozerk; Yuce, Aysel; Emre, Serap Dokmeci

    2017-10-01

    Gaucher disease (GD) is defined as an autosomal recessive disorder resulting from the deficiency of glucocerebrosidase (E.C. 3.2.1.45). Glucocerebrosidase is responsible for the degradation of glucosylceramide into ceramide and glucose. The deficiency of this enzyme results in the accumulation of undegraded glucosylceramide, almost exclusively in macrophages. With Fourier transform infrared (FTIR) spectroscopy, the complete molecular diversity of the samples can be studied comparatively and the amount of the particular materials can be determined. Also, the secondary structure ratios of proteins can be determined by analysing the amide peaks. The primary aim of this study is to introduce FTIR-ATR spectroscopy technique to GD research for the first time in the literature and to assess its potential as a new molecular method. Primary fibroblast cell cultures obtained from biopsy samples were used, since this material is widely used for the diagnosis of GD. Intact cells were placed onto a FTIR-ATR crystal and dried by purging nitrogen gas. Spectra were recorded in the mid-infrared region between 4500-850 cm-1 wavenumbers. Each peak in the spectra was assigned to as organic biomolecules according to their chemical bond information. A quantitative analysis was performed using peak areas and we also used a hierarchical cluster analysis as a multivariate spectral analysis. We obtained FTIR spectra of fibroblast samples and assigned the biomolecule origins of the peaks. We observed individual heterogeneity in FTIR spectra of GD fibroblast samples, confirming the well-known phenotypic heterogeneity in GD at the molecular level. Significant alterations in protein, lipid and carbohydrate levels related to the enzyme replacement therapy were also observed, which is also supported by cluster analysis. Our results showed that the application of FTIR spectroscopy to GD research deserves more attention and detailed studies with an increased sample size in order to evaluate its

  14. Precise Correction of Disease Mutations in Induced Pluripotent Stem Cells Derived From Patients With Limb Girdle Muscular Dystrophy.

    Science.gov (United States)

    Turan, Soeren; Farruggio, Alfonso P; Srifa, Waracharee; Day, John W; Calos, Michele P

    2016-04-01

    Limb girdle muscular dystrophies types 2B (LGMD2B) and 2D (LGMD2D) are degenerative muscle diseases caused by mutations in the dysferlin and alpha-sarcoglycan genes, respectively. Using patient-derived induced pluripotent stem cells (iPSC), we corrected the dysferlin nonsense mutation c.5713C>T; p.R1905X and the most common alpha-sarcoglycan mutation, missense c.229C>T; p.R77C, by single-stranded oligonucleotide-mediated gene editing, using the CRISPR/Cas9 gene-editing system to enhance the frequency of homology-directed repair. We demonstrated seamless, allele-specific correction at efficiencies of 0.7-1.5%. As an alternative, we also carried out precise gene addition strategies for correction of the LGMD2B iPSC by integration of wild-type dysferlin cDNA into the H11 safe harbor locus on chromosome 22, using dual integrase cassette exchange (DICE) or TALEN-assisted homologous recombination for insertion precise (THRIP). These methods employed TALENs and homologous recombination, and DICE also utilized site-specific recombinases. With DICE and THRIP, we obtained targeting efficiencies after selection of ~20%. We purified iPSC corrected by all methods and verified rescue of appropriate levels of dysferlin and alpha-sarcoglycan protein expression and correct localization, as shown by immunoblot and immunocytochemistry. In summary, we demonstrate for the first time precise correction of LGMD iPSC and validation of expression, opening the possibility of cell therapy utilizing these corrected iPSC.

  15. Duodenal endocrine cells in adult coeliac disease.

    Science.gov (United States)

    Sjölund, K; Alumets, J; Berg, N O; Håkanson, R; Sundler, F

    1979-01-01

    Using immunohistochemical techniques we studied duodenal biopsies from 18 patients with coeliac disease and 24 patients with normal duodenal morphology. We had access to antisera against the following gastrointestinal peptides: cholecystokinin (CCK), gastric inhibitory peptide (GIP), gastrin-17, glucagon-enteroglucagon, motilin, neurotensin, pancreatic peptide (PP), secretin, somatostatin, substance P and vasoactive intestinal peptide (VIP). The somatostatin, GIP, CCK, and glucagon cells were increased in number in coeliac disease. The number of motilin cells was slightly increased, while secretin cells were reduced. Cells storing gastrin-17, substance P, or neurotensin were rare in all patients regardless of diagnosis. No PP immunoreactive cells were found and VIP was localised to neurons only. In biopsies from patients having a mucosa with ridging of villi the number of the various endocrine cell types did not differ from that in the control group. Images Fig. 2 PMID:385455

  16. Increased blood clearance rate of indium-111 oxine-labeled autologous CD4+ blood cells in untreated patients with Hodgkin's disease

    International Nuclear Information System (INIS)

    Grimfors, G.; Holm, G.; Mellstedt, H.; Schnell, P.O.; Tullgren, O.; Bjoerkholm, M.

    1990-01-01

    Untreated patients with Hodgkin's disease (HD) have a blood T-lymphocytopenia mainly caused by a reduction of the CD4+ subset. Indirect support for a sequestration of T cells in the spleen and tumor-involved lymphoid tissue has accumulated. To test the hypothesis that the blood CD4 T-lymphocytopenia in patients with HD is caused by an altered lymphocyte traffic, 12 untreated HD patients and five in complete clinical remission (CCR) were studied. Blood lymphocytes were collected by leukapheresis and gradient centrifugation, and were further purified by an adherence step. The cells were labeled with indium-111 oxine and reinfused intravenously into the patient. The radioactivity of CD4+ and CD8+ blood lymphocytes separated by immunoabsorption was measured from serial blood samples. CD4+ cells were eliminated more rapidly in untreated patients than patients in CCR. Repeated gamma camera imaging after autotransfusion of indium-111 oxine labeled cells demonstrated an accumulation of radioactivity in tumor-involved tissue of untreated patients. These findings support the concept of an enhanced elimination of CD4+ cells in patients with active HD that may contribute to the observed blood T-lymphocytopenia and may reflect a biologic response to the tumor

  17. [EFFICIENCY OF COMBINATION OF ROFLUMILAST AND QUERCETIN FOR CORRECTION OXYGEN- INDEPENDENT MECHANISMS AND PHAGOCYTIC ACTIVITY OF MACROPHAGE CELLS OF PATIENTS WITH ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE WHEN COMBINED WITH CORONARY HEART DISEASE].

    Science.gov (United States)

    Gerych, P; Yatsyshyn, R

    2015-01-01

    Studied oxygen independent reaction and phagocytic activity of macrophage cells of patients with chronic obstructive pulmonary disease (COPD) II-III stage when combined with coronary heart disease (CHD). The increasing oxygen independent reactions monocytes and neutrophils and a decrease of the parameters that characterize the functional state of phagocytic cells, indicating a decrease in the functional capacity of macrophage phagocytic system (MPS) in patients with acute exacerbation of COPD, which runs as its own or in combination with stable coronary heart disease angina I-II. FC. Severity immunodeficiency state in terms of cellular component of nonspecific immunity in patients with acute exacerbation of COPD II-III stage in conjunction with the accompanying CHD increases with the progression of heart failure. Inclusion of basic therapy of COPD exacerbation and standard treatment of coronary artery disease and drug combinations Roflumilastand quercetin causes normalization of phagocytic indices MFS, indicating improved immune status and improves myocardial perfusion in terms of daily ECG monitoring.

  18. The Impact of Liver Cell Injury on Health-Related Quality of Life in Patients with Chronic Liver Disease.

    Directory of Open Access Journals (Sweden)

    Yvonne Alt

    Full Text Available Patients with chronic liver disease often suffer from unspecific symptoms and report severe impairment in the quality of life. The underlying mechanisms are multifactorial and include disease-specific but also liver related causes. The current analysis evaluated the association of hepatocellular apoptosis in non-viral chronic liver disease and health-related quality of life (HRQL. Furthermore we examined factors, which influence patient's physical and mental well-being.A total of 150 patients with non-infectious chronic liver disease were included between January 2014 and June 2015. The German version of the Chronic Liver Disease Questionnaire (CLDQ-D, a liver disease specific instrument to assess HRQL, was employed. Hepatocellular apoptosis was determined by measuring Cytokeratin 18 (CK18, M30 Apoptosense ELISA.Female gender (5.24 vs. 5.54, p = 0.04, diabetes mellitus type II (4.75 vs. 5.46, p<0.001 and daily drug intake (5.24 vs. 6.01, p = 0.003 were associated with a significant impairment in HRQL. HRQL was not significantly different between the examined liver diseases. Levels of CK18 were the highest in patients with NASH compared to all other disease entities (p<0.001. Interestingly, CK18 exhibited significant correlations with obesity (p<0.001 and hyperlipidemia (p<0.001. In patients with cirrhosis levels of CK18 correlated with the MELD score (r = 0.18, p = 0.03 and were significantly higher compared to patients without existing cirrhosis (265.5 U/l vs. 186.9U/l, p = 0.047. Additionally, CK18 showed a significant correlation with the presence and the degree of hepatic fibrosis (p = 0.003 and inflammation (p<0.001 in liver histology. Finally, there was a small negative association between CLDQ and CK18 (r = -0.16, p = 0.048.Different parameters are influencing HRQL and CK18 levels in chronic non-viral liver disease and the amount of hepatocellular apoptosis correlates with the impairment in HRQL in chronic non-viral liver diseases. These

  19. High levels of circulating VEGFR2+ Bone marrow-derived progenitor cells correlate with metastatic disease in patients with pediatric solid malignancies.

    Science.gov (United States)

    Taylor, Melissa; Rössler, Jochen; Geoerger, Birgit; Laplanche, Agnès; Hartmann, Olivier; Vassal, Gilles; Farace, Françoise

    2009-07-15

    Pediatric solid malignancies display important angiogenic potential, and blocking tumor angiogenesis represents a new therapeutic approach for these patients. Recent studies have evidenced rare circulating cells with endothelial features contributing to tumor neovascularization and have shown the pivotal role of bone marrow-derived (BMD) progenitor cells in metastatic disease progression. We measured these cells in patients with pediatric solid malignancies as a prerequisite to clinical trials with antiangiogenic therapy. Peripheral blood was drawn from 45 patients with localized (n = 23) or metastatic (n = 22) disease, and 20 healthy subjects. Subsets of circulating vascular endothelial growth factor receptor (VEGFR)2+-BMD progenitor cells, defined as CD45-CD34+VEGFR2(KDR)+7AAD- and CD45(dim)CD34+VEGFR2+7AAD- events, were measured in progenitor-enriched fractions by flow cytometry. Mature circulating endothelial cells (CEC) were measured in whole blood as CD31+CD146+CD45-7AAD- viable events. Data were correlated with VEGF and sVEGFR2 plasma levels. The CD45-CD34+VEGFR2(KDR)+7AAD- subset represented <0.003% of circulating BMD progenitor cells (< or =0.05 cells/mL). However, the median level (range) of the CD45(dim)CD34+VEGFR2+7AAD- subset was higher in patients compared with healthy subjects, 1.5% (0%-10.3%) versus 0.3% (0%-1.6%) of circulating BMD progenitors (P < 0.0001), and differed significantly between patients with localized and metastatic disease, 0.7% (0%-8.6%) versus 2.9% (0.6%-10.3%) of circulating BMD progenitors (P < 0.001). Median CEC value was 7 cells/mL (0-152 cells/mL) and similar in all groups. Unlike VEGFR2+-BMD progenitors, neither CECs, VEGF, or sVEGFR2 plasma levels correlated with disease status. High levels of circulating VEGFR2+-BMD progenitor cells correlated with metastatic disease. Our study provides novel insights for angiogenesis mechanisms in pediatric solid malignancies for which antiangiogenic targeting of VEGFR2+-BMD progenitors

  20. Retinal nerve fiber layer and ganglion cell complex thickness assessment in patients with Alzheimer disease and mild cognitive impairment. Preliminary results

    Directory of Open Access Journals (Sweden)

    A. S. Tiganov

    2014-07-01

    Full Text Available Purpose: to investigate the retinal nerve fiber layer (RNFL and the macular ganglion cell complex (GCC in patients with Alzheimer`s disease and mild cognitive impairment.Methods: this study included 10 patients (20 eyes with Alzheimer`s disease, 10 patients with mild cognitive impairment and 10 age- and sex-matched healthy controls that had no history of dementia. All the subjects underwent psychiatric examination, including the Mini-Mental State Examination (MMSE, and complete ophthalmological examination, comprising optical coherence tomography and scanning laser polarimetry.Results: there was a significant decrease in GCC thickness in patients with Alzheimer`s disease compared to the control group, global loss volume of ganglion cells was higher than in control group. there was no significant difference among the groups in terms of RNFL thickness. Weak positive correlation of GCC thickness and MMSE results was observed.Conclusion: Our data confirm the retinal involvement in Alzheimer`s disease, as reflected by loss of ganglion cells. Further studies will clear up the role and contribution of dementia in pathogenesis of optic neuropathy.

  1. Sickle Cell Anemia Disease (For Kids)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Sickle Cell Disease KidsHealth / For Kids / Sickle Cell Disease What's ... to stay in the hospital. What Causes Sickle Cell Disease? Sickle cell disease is an inherited (say: ...

  2. Celiac Disease, Enteropathy-Associated T-Cell Lymphoma, and Primary Sclerosing Cholangitis in One Patient: A Very Rare Association and Review of the Literature

    Directory of Open Access Journals (Sweden)

    N. Majid

    2013-01-01

    Full Text Available Enteropathy-associated T-cell lymphoma (EATL is a very rare peripheral T-cell lymphoma which is mostly associated with celiac disease. However, the association of primary sclerosing cholangitis and enteropathy-associated T-cell lymphoma is uncommon. Herein we report and discuss the first case of patient who presented simultaneously with these two rare diseases. It is a 54-year-old man who stopped gluten-free diet after 15 years history of celiac disease. The diagnosis was based on the histological examination of duodenal biopsy and the diagnosis of primary sclerosing cholangitis was made on liver biopsy, as well as the magnetic resonance cholangiogram. The treatment of EATL is mainly based on chemotherapy in addition to the optimal management of complications and adverse events that impact on the response to treatment and clinical outcomes, although the prognosis remains remarkably very poor.

  3. Applications of Patient-Specific Induced Pluripotent Stem Cells; Focused on Disease Modeling, Drug Screening and Therapeutic Potentials for Liver Disease

    OpenAIRE

    Chun, Yong Soon; Chaudhari, Pooja; Jang, Yoon-Young

    2010-01-01

    The recent advances in the induced pluripotent stem cell (iPSC) research have significantly changed our perspectives on regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. In this review, we describe the human iPSC generation from developmentally diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human iPSCs) and multistage hepatic differentiation protocols, and discuss both basic and clinical applications of...

  4. Does thyroidectomy, radioactive iodine therapy, or antithyroid drug treatment alter reactivity of patients` T cells to epitopes of thyrotropin receptor in autoimmune thyroid diseases?

    Energy Technology Data Exchange (ETDEWEB)

    Soliman, M.; Kaplan, E.; Abdel-Latif, A. [Univ. of Chicago, IL (United States)] [and others

    1995-08-01

    The effect of treatment on thyroid antibody production and T cell reactivity to thyroid antigens was studied in 15 patients with Graves` disease (GD) before and after thyroidectomy, 19 patients with GD before and after radioactive iodine (RAI) therapy, and 9 patients maintained euthyroid on antithyroid drugs (ATD). In GD patients, the responses of peripheral blood mononuclear cells (PBMC) and TSH receptor (TSHR)-specific T cell lines to recombinant human TSHR extracellular domain, thyroglobulin, and TSHR peptides were examined on the day of surgery or RAI therapy (day 0) and also 6-8 weeks and 3-6 months thereafter. Reactivity to TSHR peptides before surgery was heterogeneous and spanned the entire extracellular domain. Six to 8 weeks after subtotal thyroidectomy, the number of patients` PBMC responding to any peptide and the average number of recognized peptides decreased. A further decrease in the T cell reactivity to TSHR peptides was observed 3-6 months after surgery. The responses of PBMC from Graves` patients before RAI therapy were less than those in the presurgical group. Six to 8 weeks after RAI therapy, the number of patients responding to any peptide and the average number of recognized peptides increased. Three to 6 months after RAI, T cell responses to TSHR peptides were less than those 6-8 weeks after RAI therapy, but still higher than the values on day 0. Responses of PBMC from patients with GD, maintained euthyroid on ATD, were lower than those before surgery or RAI therapy. The reactivity of T cell lines in different groups reflected a pattern similar to PBMC after treatment. TSHR antibody and microsomal antibody levels decreased after surgery, but increased after RAI therapy. The difference in the number of recognized peptides by patients` PBMC before RAI and surgery may reflect the effect of long term therapy with ATD in the patients before RAI vs. the shorter period in patients before surgery. 38 refs., 2 figs., 5 tabs.

  5. Induction of systemic CTL responses in melanoma patients by dendritic cell vaccination: Cessation of CTL responses is associated with disease progression

    DEFF Research Database (Denmark)

    Andersen, M.H.; Keikavoussi, P.; Brocker, E.B.

    2001-01-01

    Two HLA-A2-positive patients with advanced stage IV melanoma were treated with monocyte-derived dendritic cells (DC) pulsed with either tumor peptide antigens from gp100, MART-1 and MAGE- 3 alone or in combination with autologous oncolysates. Clinically, the rapid progression of disease...... by Western blotting was decreased in PBL at this time. In summary, our data confirm that DC-based vaccinations induce peptide-specific T cells in the peripheral blood of advanced-stage melanoma patients. Although successful induction of systemic tumor antigen-specific CTL may not lead to objective clinical...

  6. Phase II study of a 3-day schedule with topotecan and cisplatin in patients with previously untreated small cell lung cancer and extensive disease

    DEFF Research Database (Denmark)

    Sorensen, M.; Lassen, Ulrik Niels; Jensen, Peter Buhl

    2008-01-01

    INTRODUCTION: Treatment with a topoisomerase I inhibitor in combination with a platinum results in superior or equal survival compared with etoposide-based treatment in extensive disease small cell lung cancer (SCLC). Five-day topotecan is inconvenient and therefore shorter schedules of topotecan...... and cisplatin are needed. The aim of this phase II study was to establish the response rate and response duration in chemo-naive patients with SCLC receiving a 3-day topotecan and cisplatin schedule. METHODS: Simons optimal two-stage design was used. Patients with previously untreated extensive disease SCLC...... age was 59 (range 44-74), 79% had performance status 0 or 1. Thirty-one patients completed all six cycles. Grade 3/4 anemia, neutrocytopenia, and thrombocytopenia were recorded in 9.5%, 66.7%, and 21.4% of patients, respectively. Fourteen percent of patients experienced neutropenic fever. No episodes...

  7. FoxP3(+)CD4(+)CD25(+) T cells with regulatory properties can be cultured from colonic mucosa of patients with Crohn's disease

    DEFF Research Database (Denmark)

    Rømer, Johanne Lade

    2005-01-01

    Summary CD4(+)CD25(+) regulatory T cells (T(regs)) are involved in the maintenance of peripheral tolerance and ensure a balanced immune response competent of fighting pathogens and at the same time recognizing commensals as harmless. This feature is lost in Crohn's disease (CD). The forkhead/wing......(+) T cells. Thus, we demonstrate that FoxP3(+)CD4(+)CD25(+) T cells with regulatory properties can be propagated in vitro from inflamed mucosa of CD patients, which may be of interest in adoptive immunotherapy....

  8. Cost Effectiveness of Screening Patients With Gastroesophageal Reflux Disease for Barrett's Esophagus With a Minimally Invasive Cell Sampling Device

    OpenAIRE

    Heberle, Curtis; Omidvari, A.-H. (Amir-Houshang); Ali, Ayman; Kroep, Sonja; Kong, Chung Yin; Inadomi, John; Rubenstein, J.; Tramontano, Angela C.; Dowling, E.C. (Emily C.); Hazelton, William; Luebeck, E. Georg; Lansdorp-Vogelaar, Iris; Hur, Chin

    2017-01-01

    textabstractBackground & Aims It is important to identify patients with Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma (EAC). Patients with BE usually are identified by endoscopy, which is expensive. The Cytosponge, which collects tissue from the esophagus noninvasively, could be a cost-effective tool for screening individuals with gastroesophageal reflux disease (GERD) who are at increased risk for BE. We developed a model to analyze the cost effectiveness of using the ...

  9. Effects of 5-hydroxymethyl-2-furfural on the volume and membrane permeability of red blood cells from patients with sickle cell disease

    Science.gov (United States)

    Hannemann, Anke; Cytlak, Urszula M; Rees, David C; Tewari, Sanjay; Gibson, John S

    2014-01-01

    The heterocyclic aldehyde 5-hydroxymethyl-2-furfural (5HMF) interacts allosterically with the abnormal form of haemoglobin (Hb), HbS, in red blood cells (RBCs) from patients with sickle cell disease (SCD), thereby increasing oxygen affinity and decreasing HbS polymerization and RBC sickling during hypoxia. We hypothesized that should 5HMF also inhibit the main cation pathways implicated in the dehydration of RBCs from SCD patients – the deoxygenation-induced cation pathway (Psickle), the Ca2+-activated K+ channel (the Gardos channel) and the K+–Cl− cotransporter (KCC) – it would have a synergistic effect in protection against sickling, directly through interacting with HbS, and indirectly through maintaining hydration and reducing [HbS]. This study was therefore designed to investigate the effects of 5HMF on RBC volume and K+ permeability in vitro. 5HMF markedly reduced the deoxygenation-induced dehydration of RBCs whether in response to maintained deoxygenation or to cyclical deoxygenation/re-oxygenation. 5HMF was found to inhibit Psickle, an effect which correlated with its effects on sickling. Deoxygenation-induced activation of the Gardos channel and exposure of phosphatidylserine were also inhibited, probably indirectly via reduced entry of Ca2+ through the Psickle pathway. Effects of 5HMF on KCC were more modest with a slight inhibition in N-ethylmaleimide (NEM, 1 mm)-treated RBCs and stimulation in RBCs untreated with NEM. These findings support the hypothesis that 5HMF may also be beneficial through effects on RBC ion and water homeostasis. PMID:25015917

  10. Effects of 5-hydroxymethyl-2-furfural on the volume and membrane permeability of red blood cells from patients with sickle cell disease.

    Science.gov (United States)

    Hannemann, Anke; Cytlak, Urszula M; Rees, David C; Tewari, Sanjay; Gibson, John S

    2014-09-15

    The heterocyclic aldehyde 5-hydroxymethyl-2-furfural (5HMF) interacts allosterically with the abnormal form of haemoglobin (Hb), HbS, in red blood cells (RBCs) from patients with sickle cell disease (SCD), thereby increasing oxygen affinity and decreasing HbS polymerization and RBC sickling during hypoxia. We hypothesized that should 5HMF also inhibit the main cation pathways implicated in the dehydration of RBCs from SCD patients - the deoxygenation-induced cation pathway (Psickle), the Ca(2+)-activated K(+) channel (the Gardos channel) and the K(+)-Cl(-) cotransporter (KCC) - it would have a synergistic effect in protection against sickling, directly through interacting with HbS, and indirectly through maintaining hydration and reducing [HbS]. This study was therefore designed to investigate the effects of 5HMF on RBC volume and K(+) permeability in vitro. 5HMF markedly reduced the deoxygenation-induced dehydration of RBCs whether in response to maintained deoxygenation or to cyclical deoxygenation/re-oxygenation. 5HMF was found to inhibit Psickle, an effect which correlated with its effects on sickling. Deoxygenation-induced activation of the Gardos channel and exposure of phosphatidylserine were also inhibited, probably indirectly via reduced entry of Ca(2+) through the Psickle pathway. Effects of 5HMF on KCC were more modest with a slight inhibition in N-ethylmaleimide (NEM, 1 mm)-treated RBCs and stimulation in RBCs untreated with NEM. These findings support the hypothesis that 5HMF may also be beneficial through effects on RBC ion and water homeostasis. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  11. Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease.

    Science.gov (United States)

    Trotta, Lucia; Weigt, Kathleen; Schinnerling, Katina; Geelhaar-Karsch, Anika; Oelkers, Gerrit; Biagi, Federico; Corazza, Gino Roberto; Allers, Kristina; Schneider, Thomas; Erben, Ulrike; Moos, Verena

    2017-08-01

    Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response toward Tropheryma whipplei in genetically predisposed individuals. The cofactor GrpE of heat shock protein 70 (Hsp70) from T. whipplei was previously identified as a B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific proinflammatory T-cell responses. Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before levels of CD40L, CD69, perforin, granzyme B, CD107a, and gamma interferon (IFN-γ) were determined in T cells by flow cytometry. Upon stimulation with total bacterial lysate or recombinant GrpE or Hsp70 of T. whipplei , the proportions of activated effector CD4 + T cells, determined as CD40L + IFN-γ + , were significantly lower in patients with CWD than in healthy controls; CD8 + T cells of untreated CWD patients revealed an enhanced activation toward unspecific stimulation and T. whipplei -specific degranulation, although CD69 + IFN-γ + CD8 + T cells were reduced upon stimulation with T. whipplei lysate and recombinant T. whipplei -derived proteins. Hsp70 and its cofactor GrpE are immunogenic in healthy individuals, eliciting effective responses against T. whipplei to control bacterial spreading. The lack of specific T-cell responses against these T. whipplei -derived proteins may contribute to the pathogenesis of CWD. Copyright © 2017 American Society for Microbiology.

  12. Change of Serum IgG4 in Patients with Ocular Adnexal Marginal Zone B Cell Lymphoma Associated with IgG4-Related Ophthalmic Disease After Treatment.

    Science.gov (United States)

    Wu, Yuan-Hung; Wang, Lei-Chi; Yen, Sang-Hue; Yu, Wei-Kuang; Kao, Shu-Ching; Kau, Hui-Chuan; Tsai, Chieh-Chih; Liu, Catherine Jui-Ling

    2017-09-01

    To investigate the change of serum IgG4 concentrations correlated with clinical evolution in patients with ocular adnexal marginal zone B cell lymphoma associated with IgG4-related ophthalmic disease (IgG4-ROD). Three consecutive patients with histopathologically confirmed ocular adnexal marginal zone B cell lymphoma associated with IgG4-ROD were evaluated. Two patients received radiotherapy and 1 patient received steroid therapy. Treatment outcome was evaluated by clinical symptoms, radiologic examination, and change of serum IgG4 level in these patients. All patients had elevated serum IgG4 before treatment (462, 338, and 780 mg/dL respectively.) The 2 patients who received radiotherapy achieved complete remission and the serum IgG4 decreased to 345 and 92 mg/dL, respectively. The patient who underwent systemic steroid achieved partial remission and the serum IgG4 decrease to 161 mg/dL. Our study showed elevated serum IgG4 in all patients with ocular adnexal marginal zone B cell lymphoma associated with IgG4-ROD. In addition, the elevated serum IgG4 may decrease or keep stable after treatment, accompanied by improvement in clinical symptoms and reduction of lesions.

  13. Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study

    DEFF Research Database (Denmark)

    Kastrup, Jens; Haack-Sørensen, Mandana; Juhl, Morten

    2017-01-01

    and ischemic heart failure (IHF). Batches of CSCC_ASC were isolated from three healthy donors by liposuction from abdominal adipose tissue. Adipose mesenchymal stromal cells were culture expanded in bioreactors without the use of animal constituents, cryopreserved, and stored in vials in nitrogen dry......The present first-in-human clinical trial evaluated the safety and feasibility of a newly developed and cryopreserved Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors for intramyocardial injection in ten patients with ischemic heart disease......-storage containers until use. Direct injection of CSCC_ASC into the myocardium did not cause any complications or serious adverse events related to either treatment or cell administration in a 6-month follow-up period. Four out of ten heart failure patients developed donor-specific de novo human leukocyte antigen...

  14. Cryopreserved Off-the-Shelf Allogeneic Adipose-Derived Stromal Cells for Therapy in Patients with Ischemic Heart Disease and Heart Failure-A Safety Study

    DEFF Research Database (Denmark)

    Kastrup, Jens; Haack-Sørensen, Mandana; Juhl, Morten

    2017-01-01

    The present first-in-human clinical trial evaluated the safety and feasibility of a newly developed and cryopreserved Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors for intramyocardial injection in ten patients with ischemic heart disease...... and ischemic heart failure (IHF). Batches of CSCC_ASC were isolated from three healthy donors by liposuction from abdominal adipose tissue. Adipose mesenchymal stromal cells were culture expanded in bioreactors without the use of animal constituents, cryopreserved, and stored in vials in nitrogen dry...... developed cryopreserved product CSCC_ASC from healthy donors was a safe and feasible treatment. We observed a tendency toward efficacy in patients with IHF. These findings have to be confirmed in larger placebo controlled clinical trials. Stem Cells Translational Medicine 2017;6:1963-1971....

  15. Sensitivity of whole-body CT and MRI versus projection radiography in the detection of osteolyses in patients with monoclonal plasma cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, Maya B., E-mail: m.mueller-wolf@dkfz.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); Department of Radiology, German Cancer Research Center (Dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Murray, Fritz, E-mail: fritz.murray@hotmail.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); Kilk, Kerstin, E-mail: k_fechtner@hotmail.com [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); Hillengass, Jens, E-mail: jens.hillengass@med.uni-heidelberg.de [Department of Haematology, Oncology, Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Delorme, Stefan, E-mail: s.delorme@dkfz-heidelberg.de [Department of Radiology, German Cancer Research Center (Dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Heiss, Christiane, E-mail: c.heiss@dkfz-heidelberg.de [Department of Biostatistics, German Cancer Research Center (Dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Neben, Kai, E-mail: k.neben@klinikum-mittelbaden.de [Department of Haematology, Oncology, Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Goldschmidt, Hartmut, E-mail: hartmut.goldschmidt@med.uni-heidelberg.de [Department of Haematology, Oncology, Rheumatology, University Hospital Heidelberg and National Center for Tumour Diseases, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Kauczor, Hans-Ulrich, E-mail: hu.kauczor@med.uni-heidelberg.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); and others

    2014-07-15

    Purpose: To compare sensitivity of whole-body Computed Tomography (wb-CT) and whole-body Magnetic Resonance Imaging (wb-MRI) with Projection Radiography (PR) regarding each method's ability to detect osteolyses in patients with monoclonal plasma cell disease. Patients and methods: The bone status of 171 patients was evaluated. All patients presented with multiple myeloma (MM) of all stages, monoclonal gammopathy of unknown significance (MGUS) or solitary plasmacytoma. Two groups were formed. Group A consisted of 52 patients (26 females, 26 males) with an average age of 62 years (range, 45–89 years) who received, both, PR and wb-CT as part of their diagnostic work-up. Group B comprised 119 patients (58 females, 61 males) averaging 57 years of age (range, 20–80 years) who received, both, PR and wb-MRI. Two experienced radiologists were blinded regarding the disease status and assessed the number and location of osteolyses in consensus. A distinction was made between axial and extra-axial lesions. Results: In group A, wb-CT revealed osteolyses in 12 patients (23%) that were not detected in PR. CT was superior in detecting lesions in patients with osteopenia and osteoporosis. Compared with PR, wb-CT was significantly more sensitive in detecting osteolyses than PR (p < 0.001). This was particularly true for axial lesions. Additionally, CT revealed clinically relevant incidental findings in 33 patients (63%). In group B, wb-MRI revealed lesions in 19 patients (16%) that were not detected in PR. All lesions detected by PR were also detected by wb-MRI and wb-CT. Wb-MRI and wb-CT are each superior to PR in detecting axial lesions. Conclusion: Wb-CT can detect 23% more focal lesions than PR, especially in the axial skeleton. Therefore, this imaging method should be preferred over PR in the diagnostic work-up and staging of patients with monoclonal plasma cell disease.

  16. [Chronic renal failure in sickle cell disease: A retrospective analysis of 100 adults sickle cell patients from black Africa].

    Science.gov (United States)

    Ackoundou-N'Guessan, Clément; Guei, Cyr Monley; Lagou, Delphine Amélie; Gbekedi, Serges; Tia, Mélanie Weu; Coulibaly, Pessa Albert; Nzoue, Sita; Konan, Serges; Koffi, Gustave; Gnionsahe, Daze Apollinaire

    2016-06-01

    The prevalence of chronic renal failure (CRF) in sickle cell disease (SCD) patients could vary from one country to another depending on the modalities of management. The aim of the present study was to appreciate the epidemiology of CRF in SCD patients from black Africa in order to search for promoting factors. One hundred SCD adult patients have been considered for the study. The glomerular filtration rate (GFR) has been estimated according to the CKD-EPI formula. Three groups of patients have been identified according to the value of their GFR. The mean age of the patients was 30.84±8.26 years. Male gender has represented 51% of the study population. The mean GFR value was 175.4±86.2 mL/min/1.73 m(2). The prevalence of CRF was 11%. About 3% of them had severe CRF. Subjects with normal GFR were 20%. Subjects with glomerular hyperfiltration (HF) were 69%. By univariate analysis, when subjects with HF were compared with those presenting normal GFR, the following factors have appeared to be significantly associated: female gender (female 60.9% versus male 39.1%; P60 kg; 59.9±9.41 kg; P30 years; OR=0.12 [CI95% 0.03-04]; P60 kg; OR=0.19 [CI95% 0.05-0.72]; P<0.01) were associated with HF. By univariate analysis, when subjects with CRF were compared with those presenting normal GFR, a lower hemoglobin value was significantly associated with CRF (7.92±2.7 g/dL versus 10.43±2.5 g/dL; P<0.009). There was a trend for subjects not being under maintenance therapy to more experience CRF (36.4% versus 70%; P<0.07). By logistic regression analysis, only a low hemoglobin value was associated to CRF (higher hemoglobin level; OR=0.55 [0.20-6.3]; P<0.01). In total, CRF and HF are frequent complications in SCD adult patients from black Africa. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  17. Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B-cell lymphoma patients with and without rheumatic disease

    DEFF Research Database (Denmark)

    Brauner, S; Zhou, W; Backlin, C

    2015-01-01

    OBJECTIVE: TRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21...... in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. MATERIALS AND METHODS: TRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated...... with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)-like regimen, 76 CHOP-treated and 196 rituximab-CHOP-treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR...

  18. Transcranial Doppler, MRA, and MRI as a screening examination for cerebrovascular disease in patients with sickle cell anemia: an 8-year study

    Energy Technology Data Exchange (ETDEWEB)

    Seibert, J.J.; Glasier, C.M.; Allison, J.W.; James, C.A.; Kinder, D.L.; Cox, K.S.; Lairry, F.; Graves, R.A. [Arkansas Children`s Hospital, Little Rock, AR (United States). Dept. of Radiology; Kirby, R.S.; Flick, E.L. [Center for Ambulatory Research, Univ. of Arkansas for Medical Sciences, Little Rock, AR (United States); Becton, D.L.; Jackson, F.J. [Dept. of Hematology, Univ. of Arkansas for Medical Sciences, Little Rock, AR (United States)

    1998-03-01

    Objective. The authors previously reported five transcranial Doppler ultrasonography (TCD) findings as significant in detecting clinical cerebrovascular disease in a 4-year study in patients with sickle cell disease. This is a follow-up to evaluate the validity of the original findings over another 4-year period during which the study population doubled. A clinical follow-up of the original asymptomatic sickle cell patients with positive TCD, MRA, and MRI was also made. Results. Of the 4 out of original 46 control patients in 1992 who had positive MRA and TCD, 3 have subsequently had clinical stroke. None of the 9 original patients with positive TCD and positive MRI but negative MRA have developed stroke. All five original TCD indicators of disease were still significant (P<0.05) for detecting clinical disease: maximum velocity in ophthalmic artery (OA)>35 cm/s, mean velocity in middle cerebral artery (MCA) >170 cm/s, resistive index (RI) in OA<50, velocity in OA greater than in MCA, and velocity in posterior cerebral (PCA), vertebral, or basilar arteries greater than in MCA. Four additional factors were also significant: turbulence, PCA or ACA without MCA, RI<30, and maximum velocity in MCA>200 cm/s. (orig.)

  19. Normal inhibition of DNA synthesis following γ-irradiation of radiosensitive cell lines from patients with Down's syndrome and Alzheimer's disease

    International Nuclear Information System (INIS)

    Lavin, M.F.; Le poidevin, P.; Chen, P.C.; Bates, P.

    1989-01-01

    Inhibition of DNA synthesis was studied in γ-iradiated lymphoblastoid cells from patients with Alzheimer's disease and Down's syndrome. A normal biphasic pattern of inhibition was observed over a dose range of 0-4 krad of γ-rays in all of the cell lines 3 out of 4 Down's and all the Alzheimer's cell lines were shown to be hypersensitive to ionizing radiation based on induced chromosomal aberrations. Increased G2 phase delay, comparable to that occurring in ataxia-telangiectasia cells, was observed for some of the cell lines, after exposure to γ-rays. Contrary to other data in the literature these results demonstrate that radioresistand DNA synthesis is not an intrinsic feature of all disorders characterized by radiosensitivitey. (author).; 25 refs.; 2 figs.; 1 tab

  20. Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines.

    Science.gov (United States)

    Edvardsen, Kine; Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S; Bratland, Eirik

    2015-10-01

    Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10.

  1. Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines

    Science.gov (United States)

    Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S.; Bratland, Eirik

    2015-01-01

    Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10. PMID:25978633

  2. Derivation of induced pluripotent stem cells from a familial Alzheimer's disease patient carrying the L282F mutation in presenilin 1

    DEFF Research Database (Denmark)

    Poon, Anna Fong-Yee; Li, Tong; Pires, Carlota

    2016-01-01

    Mutations in presenilin 1 (PSEN1) lead to the most aggressive form of familial Alzheimer's disease (AD). Human induced pluripotent stem cells (hiPSCs) derived from AD patients can be differentiated and used for disease modeling. Here, we derived hiPSC from skin fibroblasts obtained from an AD...... patient carrying a L282F mutation in PSEN1. We transfected skin fibroblasts with episomal iPSC reprogramming vectors targeting human OCT4, SOX2, L-MYC, KLF4, NANOG, LIN28, and short hairpin RNA against TP53. Our hiPSC line, L282F-hiPSC, displayed typical stem cell characteristics with consistent...... expression of pluripotency genes and the ability to differentiation into the three germ layers....

  3. Stem cell therapy for ischemic heart diseases.

    Science.gov (United States)

    Yu, Hong; Lu, Kai; Zhu, Jinyun; Wang, Jian'an

    2017-01-01

    Ischemic heart diseases, especially the myocardial infarction, is a major hazard problem to human health. Despite substantial advances in control of risk factors and therapies with drugs and interventions including bypass surgery and stent placement, the ischemic heart diseases usually result in heart failure (HF), which could aggravate social burden and increase the mortality rate. The current therapeutic methods to treat HF stay at delaying the disease progression without repair and regeneration of the damaged myocardium. While heart transplantation is the only effective therapy for end-stage patients, limited supply of donor heart makes it impossible to meet the substantial demand from patients with HF. Stem cell-based transplantation is one of the most promising treatment for the damaged myocardial tissue. Key recent published literatures and ClinicalTrials.gov. Stem cell-based therapy is a promising strategy for the damaged myocardial tissue. Different kinds of stem cells have their advantages for treatment of Ischemic heart diseases. The efficacy and potency of cell therapies vary significantly from trial to trial; some clinical trials did not show benefit. Diverged effects of cell therapy could be affected by cell types, sources, delivery methods, dose and their mechanisms by which delivered cells exert their effects. Understanding the origin of the regenerated cardiomyocytes, exploring the therapeutic effects of stem cell-derived exosomes and using the cell reprogram technology to improve the efficacy of cell therapy for cardiovascular diseases. Recently, stem cell-derived exosomes emerge as a critical player in paracrine mechanism of stem cell-based therapy. It is promising to exploit exosomes-based cell-free therapy for ischemic heart diseases in the future. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  4. Alzheimer's Disease and Stem Cell Therapy

    OpenAIRE

    Choi, Sung S.; Lee, Sang-Rae; Kim, Seung U.; Lee, Hong J.

    2014-01-01

    The loss of neuronal cells in the central nervous system may occur in many neurodegenerative diseases. Alzheimer's disease is a common senile disease in people over 65 years, and it causes impairment characterized by the decline of mental function, including memory loss and cognitive impairment, and affects the quality of life of patients. However, the current therapeutic strategies against AD are only to relieve symptoms, but not to cure it. Because there are only a few therapeutic strategie...

  5. In vitro regulation of immunoglobulin synthesis after marrow transplantation. I. T-cell and B-cell deficiencies in patients with and without chronic graft-versus-host disease

    International Nuclear Information System (INIS)

    Lum, L.G.; Seigneuret, M.C.; Storb, R.F.; Witherspoon, R.P.; Thomas, E.D.

    1981-01-01

    Twenty-four patients with aplastic anemia or acute leukemia were treated by marrow grafts from HLA-identical donors after conditioning with high doses of cyclophosphamide and/or today body irradiation. They were studied between 4 and 63 mo (median 14.2) after transplantation. Seventeen patients had chronic graft-versus-host disease (C-GVHD) and 7 were healthy. They were studied for defects in their T- and B-cell function using and indirect hemolytic plaque assay for Ig production after 6 days of culture in the presence of pokeweek mitogen. T or B cells from the patients with or without C-GVHD were cocultured with T or B cells from their HLA-identical marrow donors or unrelated normal controls. Intrinsic B-cell defects, lack of helper T-cell activity, and suppressor T-cell activity were more frequently found in patients with C-GVHD than in healthy patients. Fifteen of the 17 patients with C-GVHD showed on or more defects in their T-and B-cell function compared to only 3 of the 7 patients without C-GVHD. None of the healthy controls, including the marrow donors, showed defects in their T- and B-cell functions. These in vitro findings may be helpful in assessing the process of immune reconstitution and the immunologic aberration found after human marrow transplantation

  6. Generation of Xeroderma Pigmentosum-A Patient-Derived Induced Pluripotent Stem Cell Line for Use As Future Disease Model.

    Science.gov (United States)

    Ohnishi, Hiroe; Kawasaki, Takashi; Deguchi, Tomonori; Yuba, Shunsuke

    2015-08-01

    Xeroderma pigmentosum group A (XP-A) is a genetic disorder in which there is an abnormality in nucleotide excision repair that causes hypersensitivity to sunlight and multiple skin cancers. The development of central and peripheral neurological disorders not correlated to ultraviolet light exposure is associated with XP-A. The genes responsible for XP-A have been identified and a XPA knockout mouse has been generated. These knockout mice exhibit cutaneous symptoms, but they do not show neurological disorders. The mechanism of pathogenesis of neurological disorders is still unclear and therapeutic methods have not been established. Therefore, we generated XP-A patient-derived human induced pluripotent stem cells (XPA-iPSCs) to produce in vitro models of neurological disorders. We obtained iPSC lines from fibroblasts of two patients carrying different mutations. Drugs screened using XPA-iPSC lines can be helpful for treating XP-A patients in Japan. Additionally, we revealed that these iPSCs have the potential to differentiate into neural lineage cells, including dopaminergic neurons, which decrease in XP-A patients. Our results indicate that expression of the normal XPA gene without mutations is not required for generation of iPSCs and differentiation of iPSCs into neural lineage cells. XPA-iPSCs may become useful models that clarify our understanding of neurological pathogenesis and help to establish therapeutic methods.

  7. Assessing the Effect of an Educational Intervention on Nurses' and Patient Care Assistants' Comprehension and Documentation of Functional Ability in Pediatric Patients with Sickle Cell Disease.

    Science.gov (United States)

    Bernier, Katherine M; Strobel, Megan; Lucas, Ruth

    2018-04-13

    In 2014, the Youth Acute Pain Functional Ability Questionnaire (YAPFAQ) was developed to investigate patient's self-rated functional ability during times of acute pain in the inpatient clinical setting. Although it has great potential, the application of this tool has not been made a standard of care. The purpose of this multiple methods study was to determine if, through an educational intervention, hospital staff could consistently document the YAPFAQ in children with sickle cell disease (SCD) during a vaso-occlusive episode. Twenty-two staff members participated in an educational intervention and semi-structured group discussions. Pre/post surveys measured knowledge of the YAPFAQ before and after the intervention. Group discussions were recorded, transcribed verbatim, and analyzed for thematic clusters. Retrospective chart reviews of children with SCD were reviewed for YAPFAQ documentation frequency before and after the intervention. Staff knowledge of who completes the YAPFAQ increased after the intervention, (pcontinues to hold high potential for directing nursing care, but requires staff investment for clinical practice change. A seamless integration between nursing education and translation through EHR is recommended as technology continues to integrate into nursing practice. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. {sup 18}F-FDG PET/CT for detection and localization of residual or recurrent disease in patients with multiple myeloma after stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Derlin, Thorsten; Wisotzki, Christian; Klutmann, Susanne [University Medical Center Hamburg-Eppendorf, Department of Nuclear Medicine, Hamburg (Germany); Weber, Christoph; Habermann, Christian R.; Herrmann, Jochen [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Ayuk, Francis; Wolschke, Christine; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg (Germany)

    2012-03-15

    The aim of the study was to determine the diagnostic performance of {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for the detection and localization of residual or recurrent disease in patients with multiple myeloma (MM) after stem cell transplantation. A total of 197 whole-body {sup 18}F-FDG PET/CT scans were performed in 99 patients with MM at different time points in the course of disease after autologous or allogeneic stem cell transplantation. Post-transplant PET/CT scans and clinical remission status as determined by the clinical gold standard (Uniform Response Criteria) were analysed and compared. A total of 576 focal osseous and extramedullary lesions were detected in 79 scans. Additional diffuse bone marrow involvement was detected in 17 patients. {sup 18}F-FDG PET/CT had a sensitivity of 54.6%, a specificity of 82.1%, a positive predictive value of 82.3%, a negative predictive value of 54.2% and an overall accuracy of 65.5%. The sensitivity of {sup 18}F-FDG PET/CT was shown to depend on the disease category according to the Uniform Response Criteria for myeloma. In patients with MM in the post-transplant setting, {sup 18}F-FDG PET/CT may (1) contribute to the detection and localization of disease, (2) provide information about the extent of distinct myeloma manifestations and the total disease burden and (3) add information about the metabolic activity of disease, but (4) has substantially lower sensitivity for this purpose compared to the pretreatment setting. (orig.)

  9. Improvement of myocardial perfusion reserve detected by cardiovascular magnetic resonance after direct endomyocardial implantation of autologous bone marrow cells in patients with severe coronary artery disease

    Directory of Open Access Journals (Sweden)

    Lau Chu-Pak

    2010-01-01

    Full Text Available Abstract Background Recent studies suggested that bone marrow (BM cell implantation in patients with severe chronic coronary artery disease (CAD resulted in modest improvement in symptoms and cardiac function. This study sought to investigate the functional changes that occur within the chronic human ischaemic myocardium after direct endomyocardial BM cells implantation by cardiovascular magnetic resonance (CMR. Methods and Results We compared the interval changes of left ventricular ejection fraction (LVEF, myocardial perfusion reserve and the extent of myocardial scar by using late gadolinium enhancement CMR in 12 patients with severe CAD. CMR was performed at baseline and at 6 months after catheter-based direct endomyocardial autologous BM cell (n = 12 injection to viable ischaemic myocardium as guided by electromechanical mapping. In patients randomized to receive BM cell injection, there was significant decrease in percentage area of peri-infarct regions (-23.6%, P = 0.04 and increase in global LVEF (+9.0%, P = 0.02, the percentage of regional wall thickening (+13.1%, P= 0.04 and MPR (+0.25%, P = 0.03 over the target area at 6-months compared with baseline. Conclusions Direct endomyocardial implantation of autologous BM cells significantly improved global LVEF, regional wall thickening and myocardial perfusion reserve, and reduced percentage area of peri-infarct regions in patients with severe CAD.

  10. 1,25-dihydroxyvitamin D3 and dexamethasone increase interleukin-10 production in CD4+ T cells from patients with Crohn's disease

    DEFF Research Database (Denmark)

    Bartels, Lars Erik; Jørgensen, Søren Peter; Agnholt, Jørgen

    2007-01-01

    ,25-dihydroxyvitamin D3 with and without DEX could induce IL-10 production, downregulate pro-inflammatory Interferon (IFN)-gamma and Tumor Necrosis Factor (TNF)-alpha production, and influence cell kinetics in peripheral CD4+ T cells from CD patients. METHODS: CD4+ T cells were separated from peripheral blood from CD......BACKGROUND AND AIM: In Crohn's disease (CD), epidemiological data and animal studies suggest that vitamin D (vitD) has protective immune-modulating properties. 1,25-dihydroxyvitamin D3 and dexamethasone (DEX) induce interleukin (IL)-10 productions in healthy controls (HC) T cells. We studied if 1...... patients and HC. Cells were activated by anti-CD3 and anti-CD28 in the presence of 1,25-dihydroxyvitamin D3 and/or DEX. Cytokine levels, proliferation, and apoptosis were measured following 7 days of culture. RESULTS: In T cells from CD patients, 1,25-dihydroxyvitamin D3 and DEX increased IL-10 production...

  11. Mobilization Characteristics and Strategies to Improve Hematopoietic Progenitor Cell Mobilization and Collection in Patients with Chronic Granulomatous Disease and Severe Combined Immunodeficiency

    Science.gov (United States)

    Panch, Sandhya R.; Yau, Yu Ying; Kang, Elizabeth M.; De Ravin, Suk See; Malech, Harry L.; Leitman, Susan F.

    2014-01-01

    Background G-CSF mobilized autologous hematopoietic progenitor cells (HPC) may be collected by apheresis of patients with chronic granulomatous disease (CGD) and severe combined immunodeficiency (SCID) for use in gene therapy trials. CD34+ cell mobilization has not been well characterized in such patients. Study Design and Methods We retrospectively evaluated CD34+ cell mobilization and collection in 73 consecutive CGD and SCID patients and in 99 age, weight and G-CSF dose-matched healthy allogeneic controls. Results In subjects aged ≤20 years, day 5 pre-apheresis circulating CD34+ counts were significantly lower in CGD and SCID than in controls; mean peak CD34+ cells 58, 64, and 87/uL, respectively, p=0.01. The SCIDs had lower CD34+ collection efficiency than CGDs and controls; mean efficiency 40%, 63% and 57%, respectively, p=0.003. In subjects >20 years, the CGDs had significantly lower CD34+ cell mobilization than controls; mean peak CD34+ cells 41 and 113/uL, respectively, p<0.0001. In a multivariate analysis, lower sedimentation rate (ESR) at mobilization was significantly correlated with better CD34+ cell mobilization, p=0.007. In SCIDs, CD34 collection efficiency was positively correlated with higher red cell indices (MCV: R2=0.77; MCH: R2=0.94; MCHC: R2=0.7, p<0.007) but not hemoglobin. Conclusions CGD and SCID populations are characterized by significantly less robust CD34+ HPC mobilization than healthy controls. The presence of active inflammation/infection as suggested by an elevated ESR may negatively impact mobilization. Among SCIDs, markedly reduced CD34 collection efficiencies were related to iron deficiency, wherein decreased red cell size and density may impair apheresis cell separation mechanics. PMID:25143186

  12. ALS Patient Stem Cells for Unveiling Disease Signatures of Motoneuron Susceptibility: Perspectives on the Deadly Mitochondria, ER Stress and Calcium Triad

    Science.gov (United States)

    Kaus, Anjoscha; Sareen, Dhruv

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a largely sporadic progressive neurodegenerative disease affecting upper and lower motoneurons (MNs) whose specific etiology is incompletely understood. Mutations in superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TARDBP/TDP-43) and C9orf72, have been identified in subsets of familial and sporadic patients. Key associated molecular and neuropathological features include ubiquitinated TDP-43 inclusions, stress granules, aggregated dipeptide proteins from mutant C9orf72 transcripts, altered mitochondrial ultrastructure, dysregulated calcium homeostasis, oxidative and endoplasmic reticulum (ER) stress, and an unfolded protein response (UPR). Such impairments have been documented in ALS animal models; however, whether these mechanisms are initiating factors or later consequential events leading to MN vulnerability in ALS patients is debatable. Human induced pluripotent stem cells (iPSCs) are a valuable tool that could resolve this “chicken or egg” causality dilemma. Relevant systems for probing pathophysiologically affected cells from large numbers of ALS patients and discovering phenotypic disease signatures of early MN susceptibility are described. Performing unbiased ‘OMICS and high-throughput screening in relevant neural cells from a cohort of ALS patient iPSCs, and rescuing mitochondrial and ER stress impairments, can identify targeted therapeutics for increasing MN longevity in ALS. PMID:26635528

  13. Pleural lavage cytology as an independent prognostic factor in non-small-cell lung cancer patients with stage I disease and adenocarcinoma.

    Science.gov (United States)

    Hokka, Daisuke; Uchino, Kazuya; Tane, Kenta; Ogawa, Hiroyuki; Tane, Sinya; Tanaka, Yugo; Tauchi, Shunsuke; Nishio, Wataru; Yoshimura, Masahiro; Maniwa, Yoshimasa

    2015-01-01

    We previously reported that cancer cells may be detected through pleural lavage cytology (PLC). In this study, we sought to re-examine the prognostic significance of the PLC status based on an extended dataset with an additional follow-up period. Pleural lavage following thoracotomy was cytologically examined in 1,317 consecutive patients who were diagnosed with NSCLC between 1987 and 2004 at the Thoracic Surgery Units of Kobe University Graduate School of Medicine and Hyogo Cancer Center. Among the investigated patients, 46 exhibited positive cytological findings. The prognosis of these patients was significantly worse compared to that of patients without positive PLC. Of the 844 pathological stage I patients, 18 had a positive PLC status and their prognosis was significantly worse compared to that of patients with stage I disease without positive PLC. In conclusion, positive PLC findings were associated with a poor prognosis and this finding was significant for patients with stage I disease. These results suggest the need for PLC status evaluation during staging and treatment planning in patients with NSCLC.

  14. Veno-Occlusive Disease of the Liver in the Absence of Elevation in Bilirubin in Pediatric Patients after Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Myers, Kasiani C.; Dandoy, Christopher; El-Bietar, Javier; Davies, Stella M.; Jodele, Sonata

    2016-01-01

    Veno-occlusive disease (VOD) of the liver is a well-described and significant complication of hematopoietic stem cell transplantation (HSCT), with limited successful therapeutic options in severe cases. Prompt diagnosis and initiation of treatment is crucial to restrict the extent of disease. However, a subset of patients may not meet all current diagnostic criteria at presentation, and waiting for these to be met may delay therapy. We retrospectively reviewed 794 HSCT patients treated at our institution between 2003 and 2013, identifying 17 (2.1%) who developed VOD. Of these, 5 (29%) were noted to have an absence of elevated bilirubin at the time of VOD diagnosis and reversal of portal venous flow on ultrasound. Median total and conjugated bilirubin at VOD diagnosis were 1.0 and 0.2 mg/dL, respectively. All 5 patients were subsequently diagnosed with multiorgan failure associated with VOD, including 1 with encephalopathy. Four were treated with intravenous high-dose methylprednisolone (500 mg/m2 per dose every 12 hours for 6 doses). One patient received defibrotide therapy in addition to steroids and another supportive care alone. VOD resolved in 4 of 5 patients, with median time to resolution of VOD, defined as recovery of all organ function and normalization of bilirubin and portal venous flow, of 8 days. Two patients died later from progressive primary disease and chronic graft-versus-host disease, respectively. We conclude that a high index of suspicion for VOD should be maintained in patients despite lack of bilirubin elevation in the presence of other diagnostic criteria such as hepatomegaly, abdominal pain, ascites, or weight gain. Early ultrasound evaluation in these patients may lead to more timely diagnosis and therapeutic interventions. PMID:25300869

  15. Cell transplantation for Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Jia Liu; Hongyun Huang

    2006-01-01

    OBJECTIVE: The motor symptoms of Parkinson's disease (PD) can be improved by cell transplantation,which has caught general attention from the field of the therapy for PD recently. In this paper, we summarize the cell-based therapy for PD.DATA SOURCES: A search for English literature related to the cellular transplantation of PD from January 1979to July 2006 was conducted in Medline with the key words of "Parkinson's disease, cell transplantation,embryonic stem cells, neural stem cells".STUDY SELECTTON: Data were checked in the first trial, and literatures about PD and cell transplantation were selected. Inclusive criteria: ① PD; ② Cell transplantation. Exclusive criteria: repetitive researches.DATA EXTRACTTON: A total of 100 papers related to cellular transplant and PD were collected and 41literatures were in accordance with the inclusive criteria.DATA SYNTHESIS: PD is a neural degeneration disease that threatens the health of the aged people, and most traditional therapeusis cannot delay its pathological proceeding. Cell transplantation is becoming popular as a new therapeutic tool, and the cells used to transplant mainly included dopamine-secreting cells, fetal ventral mesencephalic cells, embryonic stem cells and neural stem cells up to now. Animal experiment and clinical test demonstrate that cell transplantation can relieve the motor symptoms of Parkinson's disease obviously, but there are some problems need to be solved.CONCLUSTON: Cell transplantation has visible therapeutic efficacy on PD. Following the improvement of technique, and we have enough cause to credit that cell therapy may cure PD in the future.

  16. Nationwide Survey of Patient Knowledge and Attitudes towards Human Experimentation Using Stem Cells or Bee Venom Acupuncture for Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    2014-10-01

    Full Text Available ObjectiveStem cell treatment is a well-recognized experimental treatment among patients with Parkinson’s disease (PD, for which there are high expectations of a positive impact. Acupuncture with bee venom is one of the most popular complementary and alternative treatments for PD. Patient knowledge and attitudes towards these experimental treatments are unknown. MethodsUsing a 12-item questionnaire, a nationwide survey was conducted of 963 PD patients and 267 caregivers in 44 Korean Movement Disorders Society member hospitals from April 2013 to June 2013. The survey was performed by trained interviewers using conventional methods. ResultsRegarding questions on experimental treatments using stem cells or bee venom acupuncture, 5.1–17.7% of PD patients answered questions on safety, efficacy, and evidence-based practice incorrectly; however, more than half responded that they did not know the correct answer. Although safety and efficacy have not been established, 55.5% of PD patients responded that they were willing to receive stem cell treatment. With regard to participating in experimental treatments, there was a strong correlation between stem cell treatment and bee venom acupuncture (p < 0.0001, odds ratio = 5.226, 95% confidence interval 3.919–6.969. Younger age, higher education, and a longer duration of PD were all associated with a correct understanding of experimental treatments. ConclusionsOur data suggest that relatively few PD patients correctly understand the safety and efficacy of experimental treatments and that PD patients are greatly interested in new treatments. We hope that our data will be used to educate or to plan educational programs for PD patients and caregivers.

  17. Effectiveness, safety, and cost of partial exchange transfusions in patients with sickle-cell anemia at a sickle cell disease center in sub-Saharan Africa.

    Science.gov (United States)

    Boma Muteb, P; Kaluila Mamba, J F J; Muhau Pfutila, P; Bilo, V; Panda Mulefu, J D; Diallo, D A

    2017-11-01

    The partial exchange transfusions necessary for management of some sickle-cell complications raise the issue of effectiveness in the context of limited resources and inadequate blood safety. This study evaluated the effectiveness, safety, and cost of partial exchange transfusions in 39 patients with sickle-cell anemia in Lubumbashi, looking at the patients' age and gender and the tolerability and direct cost of the transfusions. Excel and SPSS 18 were used for data entry and analysis. Chi2 and Fisher exact tests were used for comparisons. A P-value ≤ 5% was considered statistically significant. The average age of patients was 8.6 ± 6.4 years, and the majority were girls. The most frequent indications were stroke, severe infections, severe vasooclusive crises, and acute chest syndrome. Partial exchange transfusions were effective in improving hemoglobin and hematocrit as well as the percentage of HbS. No acute accident was observed during any partial exchange transfusion; one anti-Kell alloimmunization and 2 cases of iron overload were observed. The annual cost of partial exchange transfusions per patient requiring (and able to afford) regular treatment was US $ 3,345 without iron chelation and more than US $ 5000 with chelation. Partial exchange transfusions are effective and tolerated, but financially inaccessible to the majority of our sickle cell patients. Thus, an assessment is needed of the economic burden of sickle cell complications that require partial exchange transfusions in the context of countries with limited financial resources.

  18. Distribution and clonality of the vα and vβ T-cell receptor repertoire of regulatory T cells in leukemia patients with and without graft versus host disease.

    Science.gov (United States)

    Jin, Zhenyi; Wu, Xiuli; Chen, Shaohua; Yang, Lijian; Liu, Qifa; Li, Yangqiu

    2014-03-01

    Graft versus host disease (GVHD) is the main complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent data indicated that regulatory T (Treg) cells might relate to GVHD, and such functions might be mediated by certain T-cell receptor (TCR) subfamily of Treg cells. Thus, we analyzed the distribution and clonality of the TCR Vα and Vβ repertoire of Treg cells from leukemia patients with and without GVHD after allo-HSCT. Numerous TCR Vα subfamilies, including Vα1, Vα9, Vα13, Vα16-19, and Vα24-29, were absent in Treg cells after allo-HSCT. The usage numbers for the TCR Vα and Vβ subfamilies in Treg cells from patients without GVHD appeared more widely. The expression frequencies of Vα10 or Vα20 between both groups were significantly different. Moreover, the expression frequency of TCR Vβ2 subfamily in patients without GVHD was significantly higher than that in patients with GVHD. Oligoclonally expanded TCR Vα and Vβ Treg cells were identified in a few samples in both groups. Restricted utilization of the Vα and Vβ subfamilies and the absence of some important TCR rearrangements in Treg cells may be related to GVHD due to a lower regulating function of Treg subfamilies.

  19. Overexpression of GRß in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease.

    Science.gov (United States)

    Nagy, Zsolt; Acs, Bence; Butz, Henriett; Feldman, Karolina; Marta, Alexa; Szabo, Peter M; Baghy, Kornelia; Pazmany, Tamas; Racz, Karoly; Liko, Istvan; Patocs, Attila

    2016-01-01

    The glucocorticoid receptor (GR) plays a crucial role in inflammatory responses. GR has several isoforms, of which the most deeply studied are the GRα and GRß. Recently it has been suggested that in addition to its negative dominant effect on GRα, the GRß may have a GRα-independent transcriptional activity. The GRß isoform was found to be frequently overexpressed in various autoimmune diseases, including inflammatory bowel disease (IBD). In this study, we wished to test whether the gene expression profile found in a GRß overexpressing intestinal cell line (Caco-2GRß) might mimic the gene expression alterations found in patients with IBD. Whole genome microarray analysis was performed in both normal and GRß overexpressing Caco-2 cell lines with and without dexamethasone treatment. IBD-related genes were identified from a meta-analysis of 245 microarrays available in online microarray deposits performed on intestinal mucosa samples from patients with IBD and healthy individuals. The differentially expressed genes were further studied using in silico pathway analysis. Overexpression of GRß altered a large proportion of genes that were not regulated by dexamethasone suggesting that GRß may have a GRα-independent role in the regulation of gene expression. About 10% of genes differentially expressed in colonic mucosa samples from IBD patients compared to normal subjects were also detected in Caco-2 GRß intestinal cell line. Common genes are involved in cell adhesion and cell proliferation. Overexpression of GRß in intestinal cells may affect appropriate mucosal repair and intact barrier function. The proposed novel role of GRß in intestinal epithelium warrants further studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Transport of radiolabelled glycoprotein to cell surface and lysosome-like bodies of absorptive cells in cultured small-intestinal tissue from normal subjects and patients with a lysosomal storage disease

    International Nuclear Information System (INIS)

    Ginsel, L.A.; Onderwater, J.J.M.; Daems, W.T.

    1979-01-01

    The transport of 3 H-fucose and 3 H-glucosamine-labelled glycoproteins in the absorptive cells of cultured human small-intestinal tissue was investigated with light- and electron-microscopical autoradiography. The findings showed that these glycoproteins were completed in the Golgi apparatus and transported in small vesicular structures to the apical cytoplasm of these cells. Since this material arrived in the cell coat on the microvilli and in the lysosome-like bodies simultaneously, a crinophagic function of these organelles in the regulation of the transport or secretion of cell-coat material was supported. In the absorptive cells of patients with fucosidosis or Hunter's type of lysosomal storage disease, a similar transport of cell-coat material to the lysosome-like bodies and a congenital defect of a lysosomal hydrolase normally involved in the degradation of cell-coat material, can explain the accumulation of this material in the dense bodies. (orig.) [de

  1. FoxP3+CD4+CD25+ T cells with regulatory properties can be cultured from colonic mucosa of patients with Crohn's disease

    Science.gov (United States)

    Kelsen, J; Agnholt, J; Hoffmann, H J; Rømer, J L; Hvas, C L; Dahlerup, J F

    2005-01-01

    CD4+CD25+ regulatory T cells (Tregs) are involved in the maintenance of peripheral tolerance and ensure a balanced immune response competent of fighting pathogens and at the same time recognizing commensals as harmless. This feature is lost in Crohn's disease (CD). The forkhead/winged helix transcription factor FoxP3 is a master gene for Treg function and defects in the FoxP3 gene lead to a clinical picture similar to inflammatory bowel disease (IBD). Murine colitis can be cured by adoptive transfer of Tregs and ex vivo-generated gut-specific Tregs represent an attractive option for therapy in CD. Thus, defective Tregs could contribute to the development of CD. We cultured biopsies of colonic mucosa in the presence of high concentrations of interleukin (IL)-2 and IL-4 to overcome the anergic nature of naturally occurring CD4+CD25+ Tregs in the mucosa. We investigated the expression of FoxP3 and regulatory potential of gut-derived CD4+CD25+ T cells cultured from patients with CD and healthy individuals. The FoxP3 expression was analysed by reverse transcriptase polymerase chain reaction (RT-PCR), and the suppressive effect of FoxP3+CD4+CD25+ T cells on proliferation and cytokine production of autologous CD4+ T cells was assessed by flow cytometry. Cultured gut-derived T cells with CD4+CD25+ phenotype expressed FoxP3 and were able as the freshly isolated Tregs from peripheral blood to suppress proliferation and cytokine production of autologous CD4+ T cells. Thus, we demonstrate that FoxP3+CD4+CD25+ T cells with regulatory properties can be propagated in vitro from inflamed mucosa of CD patients, which may be of interest in adoptive immunotherapy. PMID:16045746

  2. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study.

    Science.gov (United States)

    Güngör, Tayfun; Teira, Pierre; Slatter, Mary; Stussi, Georg; Stepensky, Polina; Moshous, Despina; Vermont, Clementien; Ahmad, Imran; Shaw, Peter J; Telles da Cunha, José Marcos; Schlegel, Paul G; Hough, Rachel; Fasth, Anders; Kentouche, Karim; Gruhn, Bernd; Fernandes, Juliana F; Lachance, Silvy; Bredius, Robbert; Resnick, Igor B; Belohradsky, Bernd H; Gennery, Andrew; Fischer, Alain; Gaspar, H Bobby; Schanz, Urs; Seger, Reinhard; Rentsch, Katharina; Veys, Paul; Haddad, Elie; Albert, Michael H; Hassan, Moustapha

    2014-02-01

    In chronic granulomatous disease allogeneic haemopoietic stem-cell transplantation (HSCT) in adolescents and young adults and patients with high-risk disease is complicated by graft-failure, graft-versus-host disease (GVHD), and transplant-related mortality. We examined the effect of a reduced-intensity conditioning regimen designed to enhance myeloid engraftment and reduce organ toxicity in these patients. This prospective study was done at 16 centres in ten countries worldwide. Patients aged 0-40 years with chronic granulomatous disease were assessed and enrolled at the discretion of individual centres. Reduced-intensity conditioning consisted of high-dose fludarabine (30 mg/m(2) [infants HLA-matched related-donors or HLA-9/10 or HLA-10/10 matched unrelated-donors were infused. The primary endpoints were overall survival and event-free survival (EFS), probabilities of overall survival and EFS at 2 years, incidence of acute and chronic GVHD, achievement of at least 90% myeloid donor chimerism, and incidence of graft failure after at least 6 months of follow-up. 56 patients (median age 12·7 years; IQR 6·8-17·3) with chronic granulomatous disease were enrolled from June 15, 2003, to Dec 15, 2012. 42 patients (75%) had high-risk features (ie, intractable infections and autoinflammation), 25 (45%) were adolescents and young adults (age 14-39 years). 21 HLA-matched related-donor and 35 HLA-matched unrelated-donor transplants were done. Median time to engraftment was 19 days (IQR 16-22) for neutrophils and 21 days (IQR 16-25) for platelets. At median follow-up of 21 months (IQR 13-35) overall survival was 93% (52 of 56) and EFS was 89% (50 of 56). The 2-year probability of overall survival was 96% (95% CI 86·46-99·09) and of EFS was 91% (79·78-96·17). Graft-failure occurred in 5% (three of 56) of patients. The cumulative incidence of acute GVHD of grade III-IV was 4% (two of 56) and of chronic graft-versus-host disease was 7% (four of 56). Stable (≥90%) myeloid

  3. Cytokine production but lack of proliferation in peripheral blood mononuclear cells from chronic Chagas' disease cardiomyopathy patients in response to T. cruzi ribosomal P proteins.

    Directory of Open Access Journals (Sweden)

    Silvia A Longhi

    2014-06-01

    Full Text Available BACKGROUND: Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC. It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC stimulated with P2β, the C-terminal portion of P0 (CP0 proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells. CONCLUSIONS/SIGNIFICANCE: Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T

  4. Mast cell activation disease

    African Journals Online (AJOL)

    EL-HAKIM

    remodeling, wound healing, and tumor repression or growth. The broad scope .... lesions, and (iv) MC leukemia, probably representing the ..... Slow-release Vitamin C (increased degranulation of histamine; inhibition of mast cell degranulation ...

  5. Derivation, Characterization, and Neural Differentiation of Integration-Free Induced Pluripotent Stem Cell Lines from Parkinson's Disease Patients Carrying SNCA, LRRK2, PARK2, and GBA Mutations

    DEFF Research Database (Denmark)

    Momcilovic, Olga; Sivapatham, Renuka; Oron, Tal Ronnen

    2016-01-01

    We report generation of induced pluripotent stem cell (iPSC) lines from ten Parkinson's disease (PD) patients carrying SNCA, PARK2, LRRK2, and GBA mutations, and one age-matched control. After validation of pluripotency, long-term genome stability, and integration-free reprogramming, eight...... not be sufficient to determine the cause or mechanism of the disease, and highlights the need to use more focused strategies for large-scale data analysis........ We further examined gene expression in a stress model (MPTP-induced dopaminergic neuronal death) using two clones from the SNCA triplication line, and detected changes in genes associated with mitophagy. Our data suggested that even a well-characterized line of a monogenic disease may...

  6. MicroRNA expressions in PMBCs, CD4+, and CD8+ T-cells from patients suffering from autoimmune Addison's disease.

    Science.gov (United States)

    Bernecker, C; Halim, F; Haase, M; Willenberg, H S; Ehlers, M; Schott, M

    2013-08-01

    Autoimmune Addison's disease (AD) is a rare but potentially life threatening disease. The exact etiology of the immune response to the adrenal gland is still unknown. MicroRNAs (miRNAs) critically control gene-expression and play an important role in regulating the immune response. The aim of this study was to determine key immunoregulatory miRNAs influencing autoimmune adrenal insufficiency. For this purpose selected miRNAs were amplified by a semiquantitative SYBR Green PCR from blood mononuclear cells and after purification from CD4+ and CD 8+ cells of 6 patients with autoimmune adrenal insufficiency and 10 healthy controls. In CD4+ T-cells miRNA 181a*_1 (18.02 in AD vs. 11.99 in CG, p=0.0047) is significantly increased whereas miRNA 200a_1 (12.48 in AD vs. 19.40 in CG, p=0.0003) and miRNA 200a_2* (8.59 in AD vs. 17.94 in CG, p=0.0160) are significantly decreased. miRNA 200a_1 (12.37 in AD group vs. 18.12 in control group, p=0.001) and miRNA 200a_2* (10.72 in AD group vs. 17.84 in control group, p=0.022) are also significantly decreased in CD8+ T-cells. This study could show for the first time a significant change of three defined miRNAs in PBMCs, CD4+, and CD8+ T-cells of autoimmune AD patients in vivo. These data may help to better understand the cause of the autoimmune processes leading to autoimmune AD. They extend our very limited knowledge concerning miRNAs in autoimmune Addison's disease. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Hepatitis C virus in sickle cell disease.

    Science.gov (United States)

    Hassan, Mohamed; Hasan, Syed; Giday, Samuel; Alamgir, Laila; Banks, Alpha; Frederick, Winston; Smoot, Duane; Castro, Oswaldo

    2003-01-01

    PURPOSE: To determine the prevalence of hepatitis C virus antibodies (anti-HCV) in patients with sickle cell disease. PATIENTS AND METHODS: Between 1983 and 2001, 150 patients from the Howard University Hospital Center for Sickle Cell Disease were screened for HCV antibody (52% women, 48% men, mean age 34 years). Frozen serum samples from 56 adult sickle cell patients who had participated in previous surveys (1983-92) of HIV and HTLV-1 serology and who were tested in 1992 for anti-HCV antibody--when commercial ELISA test (Ortho) became available--were included in this paper. Of the 150 patients in the study, 132 had sickle cell anemia genotype (SS), 15 had sickle cell hemoglobin-C disease (SC) and three had sickle beta thalassemia. Clinical charts were reviewed for history of blood transfusion, IV drug abuse, homosexuality, tattooing, iron overload, and alcohol abuse. RESULTS: Antibodies to HCV were detected in 53 patients (35.3%). Of the 55 patients who had frozen serum samples tested in 1992, 32 (58%) were reactive for anti-HCV, while only 21 of the 95 patients (22%) tested after 1992 were positive for HCV antibodies (P<0.001). Thirty-nine of 77 patients (51%) who received more than 10 units of packed red blood cells were positive for HCV antibody, and only 14 of 61 patients (23%) who received less than 10 units of packed red blood cells transfusion were positive for HCV antibodies (P<0.001). None of the 12 patients who never received transfusion were positive for HCV antibody. In the 53 anti-HCV positive patients, the mean alanine amino-transferase (ALT) value was 98- and 81 U/L, respectively, for males and females. These values were normal for the HCV-antibody negative patients. The aspartate amino-transferase (AST) and the total bilirubin were also higher in the anti-HCV positive patients compared to patients in the anti-HCV negative group. Forty-four patients (57.1%) who were transfused more than 10 units developed iron overload defined by a serum ferritin

  8. The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

    International Nuclear Information System (INIS)

    Higginson, Daniel S.; Chen, Ronald C.; Tracton, Gregg; Morris, David E.; Halle, Jan; Rosenman, Julian G.; Stefanescu, Mihaela; Pham, Erica; Socinski, Mark A.; Marks, Lawrence B.

    2012-01-01

    Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods and Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1

  9. Impairment of Several Immune Functions and Redox State in Blood Cells of Alzheimer’s Disease Patients. Relevant Role of Neutrophils in Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Carmen Vida

    2018-01-01

    Full Text Available Since aging is considered the most risk factor for sporadic Alzheimer’s Disease (AD, the age-related impairment of the immune system (immunosenescence, based on a chronic oxidative-inflammatory stress situation, could play a key role in the development and progression of AD. Although AD is accompanied by systemic disturbance, reflecting the damage in the brain, the changes in immune response and redox-state in different types of blood cells in AD patients have been scarcely studied. The aim was to analyze the variations in several immune functions and oxidative-inflammatory stress and damage parameters in both isolated peripheral neutrophils and mononuclear blood cells, as well as in whole blood cells, from patients diagnosed with mild (mAD and severe AD, and of age-matched controls (elderly healthy subjects as well as of adult controls. The cognitive decline of all subjects was determined by Mini-Mental State Examination (MMSE test (mAD stage was established at 20 ≤ MMSE ≤ 23 score; AD stage at <18 MMSE; elderly subjects >27 MMSE. The results showed an impairment of the immune functions of human peripheral blood neutrophils and mononuclear cells of mAD and AD patients in relation to healthy elderly subjects, who showed the typical immunosenescence in comparison with the adult individuals. However, several alterations were only observed in severe AD patients (lower chemotaxis, lipopolysaccharide lymphoproliferation, and interleukin (IL-10 release; higher basal proliferation, tumor necrosis factor (TNF-α release, and IL-10/TNF-α ratio, others only in mAD subjects (higher adherence, meanwhile others appeared in both mAD and AD patients (lower phytohemaglutinin lymphoproliferation and higher IL-6 release. This impairment of immune functions could be mediated by: (1 the higher oxidative stress and damage also observed in blood cells from mAD and AD patients and in isolated neutrophils [lower glutathione (GSH levels, high oxidized

  10. Cost Effectiveness of Screening Patients With Gastroesophageal Reflux Disease for Barrett's Esophagus With a Minimally Invasive Cell Sampling Device.

    Science.gov (United States)

    Heberle, Curtis R; Omidvari, Amir-Houshang; Ali, Ayman; Kroep, Sonja; Kong, Chung Yin; Inadomi, John M; Rubenstein, Joel H; Tramontano, Angela C; Dowling, Emily C; Hazelton, William D; Luebeck, E Georg; Lansdorp-Vogelaar, Iris; Hur, Chin

    2017-09-01

    It is important to identify patients with Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma (EAC). Patients with BE usually are identified by endoscopy, which is expensive. The Cytosponge, which collects tissue from the esophagus noninvasively, could be a cost-effective tool for screening individuals with gastroesophageal reflux disease (GERD) who are at increased risk for BE. We developed a model to analyze the cost effectiveness of using the Cytosponge in first-line screening of patients with GERD for BE with endoscopic confirmation, compared with endoscopy screening only. We incorporated data from a large clinical trial of Cytosponge performance into 2 validated microsimulation models of EAC progression (the esophageal adenocarcinoma model from Massachusetts General Hospital and the microsimulation screening analysis model from Erasmus University Medical Center). The models were calibrated for US Surveillance, Epidemiology and End Results data on EAC incidence and mortality. In each model, we simulated the effect of a 1-time screen for BE in male patients with GERD, 60 years of age, using endoscopy alone or Cytosponge collection of tissue, and analysis for the level of trefoil factor 3 with endoscopic confirmation of positive results. For each strategy we recorded the number of cases of EAC that developed, the number of EAC cases detected with screening by Cytosponge only or by subsequent targeted surveillance, and the number of endoscopies needed. In addition, we recorded the cumulative costs (including indirect costs) incurred and quality-adjusted years of life lived within each strategy, discounted at a rate of 3% per year, and computed incremental cost-effectiveness ratios (ICERs) among the 3 strategies. According to the models, screening patients with GERD by Cytosponge with follow-up confirmation of positive results by endoscopy would reduce the cost of screening by 27% to 29% compared with screening by endoscopy, but led to 1.8 to 5

  11. Stem cells and respiratory diseases

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, Soraia Carvalho; Maron-Gutierrez, Tatiana; Garcia, Cristiane Sousa Nascimento Baez; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Biofisica Carlos Chagas Filho. Lab. de Investigacao]. E-mail: prmrocco@biof.ufrj.br

    2008-12-15

    Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases. (author)

  12. Stem cells and respiratory diseases

    International Nuclear Information System (INIS)

    Abreu, Soraia Carvalho; Maron-Gutierrez, Tatiana; Garcia, Cristiane Sousa Nascimento Baez; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo

    2008-01-01

    Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases. (author)

  13. Genetics Home Reference: sickle cell disease

    Science.gov (United States)

    ... Shizukuda Y, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004 Feb 26;350( ...

  14. Identification of a High-Risk Group Among Patients With Oral Cavity Squamous Cell Carcinoma and pT1–2N0 Disease

    International Nuclear Information System (INIS)

    Liao, Chun-Ta; Lin, Chien-Yu; Fan, Kang-Hsing; Wang, Hung-Ming; Ng, Shu-Hang; Lee, Li-Yu; Hsueh, Chuen; Chen, I-How; Huang, Shiang-Fu; Kang, Chung-Jan

    2012-01-01

    Purpose: In the American Joint Committee on Cancer 2010 classification system, pT1–2N0 oral cavity squamous cell carcinoma (OSCC) is considered an early-stage cancer treatable with surgery alone (National Comprehensive Cancer Network 2010 guidelines). Our aim was to evaluate the feasibility of surgery alone for pT1–2N0 OSCC patients. Methods and Materials: Among 1279 previously untreated OSCC patients referred to our hospital between January 1996 and May 2008, we identified 457 consecutive patients with pT1–2N0 disease. All had radical tumor excision with neck dissection. A total of 387 patients showing pathologic margins greater than 4 mm and treated by surgery alone were included in the final analysis. All were followed up for at least 24 months after surgery or until death. The 5-year rates of control, distant metastasis, and survival were the main outcome measures. Results: The 5-year rates in the entire group of pT1–2N0 patients were as follows: local control, 91%; neck control, 92%; distant metastases, 1%; disease-free survival, 85%; disease-specific survival, 93%; and overall survival, 84%. Multivariate analysis identified poor differentiation and pathologic tumor depth of 4 mm or greater as independent risk factors for neck control, disease-free survival, and disease-specific survival. A scoring system using poor differentiation and tumor depth was formulated to define distinct prognostic groups. The presence of both poorly differentiated tumors and a tumor depth of 4 mm or greater resulted in significantly poorer 5-year neck control (p < 0.0001), disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p = 0.0046) rates. Conclusion: The combination of poor differentiation and pathologic tumor depth of 4 mm or greater identified a subset of pT1–2N0 OSCC patients with poor outcome, who may have clinical benefit from postoperative adjuvant radiotherapy.

  15. Identification of a High-Risk Group Among Patients With Oral Cavity Squamous Cell Carcinoma and pT1-2N0 Disease

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Chun-Ta [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Lin, Chien-Yu [Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Radiation Oncology, Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Sciences of Chang Gung University, Taoyuan, Taiwan (China); Fan, Kang-Hsing [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Radiation Oncology, Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Sciences of Chang Gung University, Taoyuan, Taiwan (China); Wang, Hung-Ming [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Hema-Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Ng, Shu-Hang [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Diagnostic Radiology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Lee, Li-Yu; Hsueh, Chuen [Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Chen, I-How; Huang, Shiang-Fu; Kang, Chung-Jan [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); and others

    2012-01-01

    Purpose: In the American Joint Committee on Cancer 2010 classification system, pT1-2N0 oral cavity squamous cell carcinoma (OSCC) is considered an early-stage cancer treatable with surgery alone (National Comprehensive Cancer Network 2010 guidelines). Our aim was to evaluate the feasibility of surgery alone for pT1-2N0 OSCC patients. Methods and Materials: Among 1279 previously untreated OSCC patients referred to our hospital between January 1996 and May 2008, we identified 457 consecutive patients with pT1-2N0 disease. All had radical tumor excision with neck dissection. A total of 387 patients showing pathologic margins greater than 4 mm and treated by surgery alone were included in the final analysis. All were followed up for at least 24 months after surgery or until death. The 5-year rates of control, distant metastasis, and survival were the main outcome measures. Results: The 5-year rates in the entire group of pT1-2N0 patients were as follows: local control, 91%; neck control, 92%; distant metastases, 1%; disease-free survival, 85%; disease-specific survival, 93%; and overall survival, 84%. Multivariate analysis identified poor differentiation and pathologic tumor depth of 4 mm or greater as independent risk factors for neck control, disease-free survival, and disease-specific survival. A scoring system using poor differentiation and tumor depth was formulated to define distinct prognostic groups. The presence of both poorly differentiated tumors and a tumor depth of 4 mm or greater resulted in significantly poorer 5-year neck control (p < 0.0001), disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p = 0.0046) rates. Conclusion: The combination of poor differentiation and pathologic tumor depth of 4 mm or greater identified a subset of pT1-2N0 OSCC patients with poor outcome, who may have clinical benefit from postoperative adjuvant radiotherapy.

  16. Socio-demographic characteristics and psychosocial consequences of sickle cell disease: the case of patients in a public hospital in Ghana.

    Science.gov (United States)

    Adzika, Vincent A; Glozah, Franklin N; Ayim-Aboagye, Desmond; Ahorlu, Collins S K

    2017-01-31

    Sickle cell disease (SCD) is of major public health concern globally, with majority of patients living in Africa. Despite its relevance, there is a dearth of research to determine the socio-demographic distribution and psychosocial impact of SCD in Ghana. The objective of this study was to examine the socio-demographic distribution and psychosocial consequences of SCD among patients in Ghana and to assess their quality of life and coping mechanisms. A cross-sectional research design was used that involved the completion of questionnaires on socio-demographic characteristics, quality of life, coping mechanisms, anxiety and depression. Participants were 387 male and female patients attending a sickle cell clinic in a public hospital. Results showed that majority of the patients were single, female, less than 39 years old and had attained secondary school level of education or less. Also, patients were more satisfied by the presence of love, friends and relatives as well as home, community and neighbourhood environment. While pains of varied nature and severity were the major reasons for attending hospital in SCD condition, going to the hospital as well as having faith in God was the most frequently reported mechanisms for coping with an unbearable SCD attacks. Results of multiple regression analysis showed that some socio-demographic and quality of life indicators had strong associations with anxiety and/or depression. It is recommended that a holistic intervention strategy incorporating psychosocial dimensions should be considered in the treatment and management of SCD.

  17. Patients with sickle cell disease are frequently excluded from the benefits of transcranial doppler screening for the risk of stroke despite extensive and compelling evidence

    Directory of Open Access Journals (Sweden)

    Daniela Laranja Gomes Rodrigues

    Full Text Available ABSTRACT Transcranial doppler (TCD is a strategic component of primary stroke prevention in children with sickle cell disease (SCD. This study was conducted to examine the TCD characteristics of children with SCD in nine different medical centers in Brazil. Methods: Transcranial doppler was performed in accordance with the Stroke Prevention Trial in Sickle Cell Anemia Protocol. Results: Of the 396 patients, 69.5% had homozygous SS hemoglobin. The TCD result was abnormal in 4.8%, conditional in 12.6%, inadequate in 4.3% and abnormally low in 1% of patients. The highest mean flow velocities were 121±23.83cm/s and 124±27.21cm/s in the left and right middle cerebral artery respectively. A total of 28.8% patients (mean age 9.19±5.92 years were evaluated with TCD for the first time. Conclusions: The SCD patients were evaluated with TCD at an older age, representing an important missed opportunity for stroke prevention. Since TCD screening in patients with SCD is important to detect those at high risk for stroke, it is recommended that this screening should be made more readily available.

  18. [Partial splenectomy in sickle cell disease].

    Science.gov (United States)

    Gutiérrez Díaz, A I; Svarch, E; Arencibia Núñez, A; Sabournin Ferrier, V; Machín García, S; Menendez Veitía, A; Ramón Rodriguez, L; Serrano Mirabal, J; García Peralta, T; López Martin, L G

    2015-04-01

    Total splenectomy in sickle cell disease is related to a high risk of fulminant sepsis and increased incidence of other events, which have not been reported in patients with partial splenectomy. In this study we examined the patients with sickle cell disease and partial splenectomy and compared the clinical and laboratory results with non-splenectomized patients. We studied 54 patients with sickle cell disease who underwent partial splenectomy in childhood from 1986 until 2011 at the Institute of Hematology and Immunology. They were compared with 54 non-splenectomized patients selected by random sampling with similar characteristics. Partial splenectomy was performed at a mean age of 4.1 years, with a higher frequency in homozygous hemoglobin S (70.4%), and the most common cause was recurrent splenic sequestration crisis. The most common postoperative complications were fever of unknown origin (14.8%) and acute chest syndrome (11.1%). After splenectomy there was a significant increase in leukocytes, neutrophils, and platelets, the latter two parameters remained significantly elevated when compared with non-splenectomized patients. There was no difference in the incidence of clinical events, except hepatic sequestration, which was more common in splenectomized patients. Partial splenectomy was a safe procedure in patients with sickle cell disease. There were no differences in the clinical picture in children splenectomized and non-splenectomized except the greater frequency of hepatic sequestration crisis in the first group. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  19. Progressive rise in red cell distribution width is associated with disease progression in ambulatory patients with chronic heart failure.

    Science.gov (United States)

    Cauthen, Clay A; Tong, Wilson; Jain, Anil; Tang, W H Wilson

    2012-02-01

    Single red cell distribution width (RDW) assessment is a consistent prognostic marker of poor outcomes in heart failure as well as in other patient cohorts. The objective of this study was to determine the prognostic value of sequential RDW assessment in ambulatory patients with chronic heart failure. We reviewed 6,159 consecutive ambulatory patients with chronic heart failure between 2001-2006 and examined changes in RDW values from baseline to 1-year follow-up. Clinical, demographic, laboratory, and ICD-9 coding data were extracted from electronic health records, and all-cause mortality was followed over a mean follow-up of 4.4 ± 2.4 years. In this study cohort, median baseline RDW was 14.9%. RDW >16% at baseline (18.5% of cohort) was associated with a higher mortality rates than RDW ≤16%. For each +1% increment of baseline RDW, the risk ratio for all-cause mortality was 1.17 (95% confidence interval [CI] 1.15-1.19; P < .0001). At 12-month follow-up (n = 1,601), a large majority of subjects (68% in first tertile, 56% in second tertile of baseline RDW) showed rising RDW and correspondingly higher risk for all-cause mortality (risk ratio for +1% increase in changes in RDW was 1.08 (95% CI 1.03-1.13; P = .001). This effect was independent of anemia status or other baseline cardiac or renal indices, and particularly strong in those with lower baseline RDW. In our ambulatory cohort of patients with chronic heart failure, baseline and serial increases in RDW were associated with poor long-term outcomes independently from standard cardiac, hematologic, and renal indices. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Sickle cell disease in childhood in Madina

    International Nuclear Information System (INIS)

    Hawasawi, Zakaria M.; Nabi, G.; Al-Magamci, M.S.F.; Awad, Khalid S.

    1998-01-01

    Sickle cell disease (SCD) is a common disease in Saudi Arabia, with ahigh prevalence in the Eastern and Southern regions. This study reports on 53cases of SCD encountered in the Madina area. In a retrospective study of 6000pediatric patients, 53 children (0.88%) with sickle cell disease wereadmitted in the Maternity and Children's Hospital Madina, between November1990 and October 1991. Of these, 39 patients (73.58%) were Saudis and 14(26.41%) were non-Saudis. Thirty-six patients were homozygous SS and 17 weresickle thalassemic. The main causes of admission were vaso-occlusive crisis(77.35%), infection (67.92%), acute chest syndrome (22.64%), anemia (12.6%)and cerebrovascular accident (9.43%). The lowest and highest age groupsrecorded in this study were six months and 12 years, respectively. About 70%of patients are still being followed-up, and none of the patients has died.This disease is one of the major causes of morbidity in this region of SaudiArabia. Measures required include neonatal screening programs for the earlydetection of the disease as well as research into new drugs to counter thedisease. (author)

  1. 2D ultrasonography and contrast enhanced ultrasound for the evaluation of cavitating mesenteric lymph node syndrome in a patient with refractory celiac disease and enteropathy T cell lymphoma

    Directory of Open Access Journals (Sweden)

    Pojoga Cristina

    2013-02-01

    Full Text Available Abstract Background The cavitating mesenteric lymph node syndrome (CMLNS is a rare manifestation of celiac disease, with an estimated mortality rate of 50%. Specific infections and malignant lymphoma may complicate its clinical course and contribute to its poor prognosis. Diagnosing the underlying cause of CMLNS can be challenging. This is the first report on contrast enhanced ultrasound (CEUS findings in enteropathy associated T-cell lymphoma (EATL complicating CMLNS in a gluten-free compliant patient with persistent symptoms and poor outcome. Case presentation We present the case of a 51-year old Caucasian male patient, diagnosed with celiac disease and CMLNS. Despite his compliance to the gluten-free diet the symptoms persisted and we eventually considered the possible development of malignancy. No mucosal changes suggestive of lymphoma were identified with capsule endoscopy. Low attenuation mesenteric lymphadenopathy, without enlarged small bowel segments were seen on computed tomography. CEUS revealed arterial rim enhancement around the necrotic mesenteric lymph nodes, without venous wash-out. No malignant cells were identified on laparoscopic mesenteric lymph nodes biopsies. The patient died due to fulminant liver failure 14 months later; the histopathological examination revealed CD3/CD30-positive atypical T-cell lymphocytes in the liver, mesenteric tissue, spleen, gastric wall, kidney, lung and bone marrow samples; no malignant cells were present in the small bowel samples. Conclusions CEUS findings in EATL complicating CMLNS include arterial rim enhancement of the mesenteric tissue around the cavitating lymph nodes, without venous wash-out. This vascular pattern is not suggestive for neoangiogenesis, as arteriovenous shunts from malignant tissues are responsible for rapid venous wash-out of the contrast agent. CEUS failed to provide a diagnosis in this case.

  2. Pilot randomized controlled trial to evaluate the effect of aquatic and land physical therapy on musculoskeletal dysfunction of sickle cell disease patients

    Directory of Open Access Journals (Sweden)

    Camila Tatiana Zanoni

    2015-04-01

    Full Text Available Objective: To compare the effect of aquatic and land-based physiotherapy in reducing musculoskeletal hip and lower back pain and increasing overall physical capabilities of sickle cell disease patients. Methods: Informed written consent was obtained from all volunteers who were submitted to evaluations using different functional scales: Lequesne's Algofunctional Questionnaire and Oswestry Disability Index, trunk and hip range of motion, goniometry, trunk and hip muscle strength assessment using load cell, and surface electromyography of the iliocostalis, long dorsal (longissimus, gluteus maximus, gluteus medius and tensor fasciae latae muscles. Ten patients were randomized into two groups: aquatic physiotherapy with a mean age of 42 years (range: 25-67 and conventional physiotherapy with a mean age of 49 years (range: 43-59. Both groups were submitted to a twelve-week program of two sessions weekly. Results: After the intervention, significant improvements were observed regarding the Lequesne index (p-value = 0.0217, Oswestry Disability Index (p-value = 0.0112, range of motion of trunk extension (p-value = 0.0320, trunk flexion muscle strength (p-value = 0.0459, hip extension and abduction muscle strength (p-value = 0.0062 and p-value = 0.0257, respec- tively. Range of motion of trunk and hip flexion, extension, adduction and abduction, trunk extensor muscle strength and all surface electromyography variables showed no significant statistical difference. Conclusion: Physical therapy is efficient to treat musculoskeletal dysfunctions in sickle cell disease patients, irrespective of the technique; however, aquatic therapy showed a trend toward improvement in muscle strength. Further studies with a larger patient sample and longer periods of therapy are necessary to confirm these results.

  3. Cerebro vascular accident in sickle cell disease

    International Nuclear Information System (INIS)

    Alam, M.; Lodhi, M.A.; Khan, D.

    2003-01-01

    Sickle cell disease (SCD) is a common inherited hemoglobin disorder characterized by the presence of sickle shaped erythrocytes in the blood. It can cause stroke in around 10% of children. Repeated blood transfusions are often used in an attempt to dilute blood thus reducing the risk of vaso-occlusion and stroke. We report a case of an 11 years old girl, known patient of sickle cell disease, who did not follow regular blood transfusion protocol and as a result presented with recurrent stroke. (author)

  4. Advanced sickle cell associated interstitial lung disease presenting ...

    African Journals Online (AJOL)

    Previous studies have reported abnormal pulmonary function and pulmonary hypertension among Nigerians with sickle cell disease, but there is no report of interstitial lung disease among them. We report a Nigerian sickle cell patient who presented with computed tomography proven interstitial lung disease complicated by ...

  5. Inhibition of Progenitor Dendritic Cell Maturation by Plasma from Patients with Peripartum Cardiomyopathy: Role in Pregnancy-associated Heart Disease

    Directory of Open Access Journals (Sweden)

    Jane E. Ellis

    2005-01-01

    Full Text Available Dendritic cells (DCs play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12 of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF- were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs was significantly reduced (p < 0.001 in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM.

  6. Prediction of disease-free survival by the PET/CT radiomic signature in non-small cell lung cancer patients undergoing surgery

    Energy Technology Data Exchange (ETDEWEB)

    Kirienko, Margarita; Fogliata, Antonella; Sollini, Martina [Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan (Italy); Cozzi, Luca [Humanitas Clinical and Research Center, Radiotherapy and Radiosurgery, Rozzano, Milan (Italy); Antunovic, Lidija [Humanitas Clinical and Research Center, Nuclear Medicine, Rozzano, Milan (Italy); Lozza, Lisa [Orobix Srl, Bergamo (Italy); Voulaz, Emanuele [Humanitas Clinical and Research Center, Thoracic Surgery, Rozzano, Milan (Italy); Rossi, Alexia [Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan (Italy); Humanitas Clinical and Research Center, Radiology, Rozzano, Milan (Italy); Chiti, Arturo [Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan (Italy); Humanitas Clinical and Research Center, Nuclear Medicine, Rozzano, Milan (Italy)

    2018-02-15

    Radiomic features derived from the texture analysis of different imaging modalities e show promise in lesion characterisation, response prediction, and prognostication in lung cancer patients. The present study aimed to identify an images-based radiomic signature capable of predicting disease-free survival (DFS) in non-small cell lung cancer (NSCLC) patients undergoing surgery. A cohort of 295 patients was selected. Clinical parameters (age, sex, histological type, tumour grade, and stage) were recorded for all patients. The endpoint of this study was DFS. Both computed tomography (CT) and fluorodeoxyglucose positron emission tomography (PET) images generated from the PET/CT scanner were analysed. Textural features were calculated using the LifeX package. Statistical analysis was performed using the R platform. The datasets were separated into two cohorts by random selection to perform training and validation of the statistical models. Predictors were fed into a multivariate Cox proportional hazard regression model and the receiver operating characteristic (ROC) curve as well as the corresponding area under the curve (AUC) were computed for each model built. The Cox models that included radiomic features for the CT, the PET, and the PET+CT images resulted in an AUC of 0.75 (95%CI: 0.65-0.85), 0.68 (95%CI: 0.57-0.80), and 0.68 (95%CI: 0.58-0.74), respectively. The addition of clinical predictors to the Cox models resulted in an AUC of 0.61 (95%CI: 0.51-0.69), 0.64 (95%CI: 0.53-0.75), and 0.65 (95%CI: 0.50-0.72) for the CT, the PET, and the PET+CT images, respectively. A radiomic signature, for either CT, PET, or PET/CT images, has been identified and validated for the prediction of disease-free survival in patients with non-small cell lung cancer treated by surgery. (orig.)

  7. Risk Factors Associated with Disease Recurrence in Patients with Stage III/IV Squamous Cell Carcinoma of the Oral Cavity Treated with Surgery and Postoperative Radiotherapy.

    Science.gov (United States)

    Noble, Anisha R; Greskovich, John F; Han, Jaehong; Reddy, Chandana A; Nwizu, Tobenna I; Khan, Mumtaz F; Scharpf, Joseph; Adelstein, David J; Burkey, Brian B; Koyfman, Shlomo A

    2016-02-01

    The purpose of the present study was to identify variables associated with high risk of failure in patients with locally advanced squamous cell carcinoma of the oral cavity (SCC-OC). This retrospective study included 191 patients with stage III-IVb SCC-OC treated with post-operative radiotherapy (RT) or chemoradiotherapy (CRT) between 1995 and 2013. Disease-free (DFS) and overall survival (OS) were analyzed; variables associated with inferior DFS were identified. Seventy-five patients (39%) recurred. DFS and five-year OS were 52% and 54%, respectively. Poorly differentiated tumors (p=0.03), recurrent tumors (p=0.02) and high nodal ratio (p=0.02) were associated with an increased risk of recurrence. CRT was associated with improved DFS in patients with positive margins and/or extracapsular extension (p=0.021). Tumors that are recurrent, high grade, or have high nodal ratio are at risk of recurrence. Presence of these disease features should be taken into consideration for better risk stratification. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. Rheumatic Disease Autoantibodies in Patients with Autoimmune Thyroid Diseases.

    Science.gov (United States)

    Nisihara, Renato; Pigosso, Yasmine; Prado, Nathalia; Utiyama, Shirley R R; Carvalho, Gisah; Skare, Thelma

    2018-06-04

    Patients with autoimmune thyroid diseases (ATD) such as Graves' disease (GD) and Hashimoto thyroiditis (HT) may have non-organ specific autoantibodies such as ANA (antinuclear antibodies) and RF (rheumatoid factor). To study the prevalence of rheumatic autoantibodies in a group of ATD patients without known rheumatic diseases and to evaluate its association with the patients' epidemiological and treatment profile. To follow positive non-organ specific autoantibody-positive ATD individuals to investigate whether they will develop a rheumatic disorder. A sample of 154 ATD patients (70 HT and 84 GD; mean age 45.3 ± 14.2) had determination of ANA by immunofluorescence, using hep-2 cells as substrate, extractable nuclear antigen (ENA) profile by ELISA kits and RF by latex agglutination. Epidemiological and treatment profile were obtained through chart review. These patients were followed for the mean period of five years, between 2010 to 2015. Positive ANA was found in 17.5% (27/154) of the patients: anti-Ro/SS-A in 4/154 (2.5%); anti-RNP in 4/154 (2.5%) and anti-La/SS-B in 3/154 (1.9%). None had anti-Sm antibodies. RF was detected in 12/154 (7.7%) of ATD patients and was more common in older individuals (p = 0.007). There was a positive association between the presence of RF and ANA (p = 0.03; OR = 3.89; 95% CI = 1.1-13.3). None of the patients with positive autoantibodies developed clinical rheumatic diseases during the period of observation. We found rheumatic autoantibodies in 17.5% of ATD patients without rheumatic diseases. None of them were associated with the appearance of clinical rheumatic disorder during the period of five years. ©2018The Author(s). Published by S. Karger AG, Basel.

  9. Increased rho kinase activity in mononuclear cells of dialysis and stage 3-4 chronic kidney disease patients with left ventricular hypertrophy: Cardiovascular risk implications.

    Science.gov (United States)

    Calò, Lorenzo A; Vertolli, Ugo; Pagnin, Elisa; Ravarotto, Verdiana; Davis, Paul A; Lupia, Mario; Naso, Elena; Maiolino, Giuseppe; Naso, Agostino

    2016-03-01

    Cardiovascular disease (CVD) is the leading cause of excess mortality in chronic kidney disease (CKD) and dialysis patients (DP) who have higher prevalence of left ventricular hypertrophy (LVH), the strongest predictor of CV events. Rho kinase (ROCK) activation is linked in hypertensive patients to cardiac remodeling while ROCK inhibition suppresses cardiomyocyte hypertrophy and, in a human clinical condition opposite to hypertension, its downregulation associates with lack of CV remodeling. Information on ROCK activation-LVH link in CKD and DP is lacking. Mononuclear cells (PBMCs) MYPT-1 phosphorylation, a marker of ROCK activity, and the effect of fasudil, a ROCK inhibitor, on MYPT-1 phosphorylation were assessed in 23 DPs, 13 stage 3-4 CKD and 36 healthy subjects (HS) by Western blot. LV mass was assessed by M-mode echocardiography. DP and CKD had higher MYPT-1 phosphorylation compared to HS (p<0.001 and p=0.003). Fasudil (500 and 1000μM) dose dependently reduced MYPT-1 phosphorylation in DP (p<0.01). DP had higher LV mass than CKD (p<0.001). MYPT-1 phosphorylation was higher in patients with LVH (p=0.009) and correlated with LV mass both in DP and CKD with LVH (p<0.001 and p=0.006). In DP and CKD, ROCK activity tracks with LVH. This ROCK activation-LVH link provided in these CVD high-risk patients along with similar findings in hypertensive patients and added to opposite findings in a human model opposite to hypertension and in type 2 diabetic patients, identify ROCK activation as a potential LVH marker and provide further rationale for ROCK activation inhibition as target of therapy in CVD high-risk patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Diagnostic values for the viral load in peripheral blood mononuclear cells of patients with chronic active Epstein-Barr virus disease.

    Science.gov (United States)

    Ito, Yoshinori; Suzuki, Michio; Kawada, Jun-ichi; Kimura, Hiroshi

    2016-04-01

    Chronic active Epstein-Barr virus disease (CAEBV) is a distinct EBV-associated lymphoproliferative disease with a poor prognosis. Although the viral load in blood samples has been widely used for diagnosing CAEBV, well-defined viral load thresholds to guide clinicians are currently lacking. The aim of the present study was to determine standardized diagnostic values for EBV load in blood samples of CAEBV patients using the World Health Organization international standard for reporting. Levels of EBV DNA in 103 peripheral blood mononuclear cells (PBMCs) and 95 plasma/serum samples from 107 cases with CAEBV were quantified and expressed in international units. Receiver operating characteristic curves were analyzed to assess the most appropriate cut-off values for levels of EBV DNA to distinguish CAEBV from EBV-associated infectious mononucleosis (IM) and controls with past EBV infection. Levels of EBV DNA in PBMCs were significantly higher in the CAEBV group (median, 10(4.2) IU/μgDNA) compared to the IM (median, 10(2.1) IU/μgDNA) and control groups. An inconsistent qualitative result was seen in 13 of 86 CAEBV patients; in these, EBV-DNA was positive in PBMCs, but negative in plasma. Diagnostic cut-off values for viral load in PBMCs from CAEBV patients, as compared to those of healthy controls and IM patients, were 10(2.0) IU/μgDNA and 10(3.2) IU/μgDNA, respectively. For diagnostic purposes, the viral load of PBMCs was better than of plasma/serum. A diagnostic cut-off EBV load for CAEBV may be useful for the management of CAEBV patients. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... that includes studying more complex 3D cell cultures, as well as accelerating aging of the neurons, may help to yield stronger phenotypes in the cultured cells. Thus, the use and application of pluripotent stem cells for modelling disease have already shown to be a powerful approach for discovering more about...

  12. NKT cells in cardiovascular diseases.

    Science.gov (United States)

    van Puijvelde, Gijs H M; Kuiper, Johan

    2017-12-05

    Despite life-style advice and the prescription of cholesterol-lowering and anti-thrombotic drugs, cardiovascular diseases are still the leading cause of death worldwide. Therefore, there is an urgent need for new therapeutic strategies focussing on atherosclerosis, the major underlying pathology of cardiovascular diseases characterized by an accumulation of lipids in an inflamed arterial/vessel wall. CD1d-restricted lipid-sensing natural killer T (NKT) cells, bridging the innate and adaptive immunity, and CD1d-expressing antigen-presenting cells are detected in atherosclerotic lesions of mice and humans. In this review we will summarize studies that point to a critical role for NKT cells in the pathogenesis of atherosclerosis and other cardiovascular diseases by the secretion of pro-atherogenic cytokines and cytotoxins. These pro-atherogenic NKT cells are potential targets for new therapeutic strategies in the prevention and treatment of cardiovascular diseases. Additionally, proteins transferring lipids during atherosclerosis, which are also important in the loading of lipids onto CD1d and possible endogenous ligands responsible for the activation of NKT cells during atherosclerosis will be discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Bevacizumab Demonstrates Prolonged Disease Stabilization in Patients with Heavily Pretreated Metastatic Renal Cell Carcinoma: A Case Series and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Nicole M. Agostino

    2010-01-01

    Full Text Available There are now a variety of therapies approved for the treatment of metastatic renal cell carcinoma (RCC. These include the immunotherapeutics, alfa-interferon, and interleukin-2, and agents that target the vascular endothelial growth factor receptor (VEGFR via its tyrosine kinase, such as sorafenib, sunitinib, and pazopanib, or the mammalian target of rapamycin (mTOR, such as temsirolimus and everolimus. Bevacizumab, a monoclonal antibody directed against the ligand, VEGF, has shown activity against RCC as a single agent in patients who had failed prior cytokine therapy and as first line therapy in combination with interferon. The activity of bevacizumab in patients who had received and failed prior therapy has not been described. We report our experience in 4 patients with metastatic RCC who had failed prior cytokine, TKI, and mTOR inhibitors who were treated with bevacizumab as single agent therapy. These heavily pretreated patients sustained very prolonged periods of stable disease (median of 12 months with very little toxicity and excellent quality of life. The activity of this agent in patients who had failed prior therapies directed against the VEGFR and mTOR suggests that therapy targeting the ligand, VEGF, is still a viable approach in these patients and deserves further study.

  14. Stem cell treatment for chronic lung diseases.

    Science.gov (United States)

    Tzouvelekis, Argyris; Ntolios, Paschalis; Bouros, Demosthenes

    2013-01-01

    Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. In view of the current disappointing status of available pharmaceutical agents, there is an urgent need for alternative more effective therapeutic approaches that will not only help to relieve patient symptoms but will also affect the natural course of the respective disease. Regenerative medicine represents a promising option with several fruitful therapeutic applications in patients suffering from chronic lung diseases. Nevertheless, despite relative enthusiasm arising from experimental data, application of stem cell therapy in the clinical setting has been severely hampered by several safety concerns arising from the major lack of knowledge on the fate of exogenously administered stem cells within chronically injured lung as well as the mechanisms regulating the activation of resident progenitor cells. On the other hand, salient data arising from few 'brave' pilot investigations of the safety of stem cell treatment in chronic lung diseases seem promising. The main scope of this review article is to summarize the current state of knowledge regarding the application status of stem cell treatment in chronic lung diseases, address important safety and efficacy issues and present future challenges and perspectives. In this review, we argue in favor of large multicenter clinical trials setting realistic goals to assess treatment efficacy. We propose the use of biomarkers that reflect clinically inconspicuous alterations of the disease molecular phenotype before rigid conclusions can be safely drawn. Copyright © 2013 S. Karger AG, Basel.

  15. Dysregulation of endothelial colony-forming cell function by a negative feedback loop of circulating miR-146a and -146b in cardiovascular disease patients.

    Directory of Open Access Journals (Sweden)

    Ting-Yu Chang

    Full Text Available Functional impairment of endothelial colony-forming cells (ECFCs, a specific cell lineage of endothelial progenitor cells (EPCs is highly associated with the severity of coronary artery disease (CAD, the most common type of cardiovascular disease (CVD. Emerging evidence show that circulating microRNAs (miRNAs in CAD patients' body fluid hold a great potential as biomarkers. However, our knowledge of the role of circulating miRNA in regulating the function of ECFCs and the progression of CAD is still in its infancy. We showed that when ECFCs from healthy volunteers were incubated with conditioned medium or purified exosomes of cultured CAD ECFCs, the secretory factors from CAD ECFCs dysregulated migration and tube formation ability of healthy ECFCs. It is known that exosomes influence the physiology of recipient cells by introducing RNAs including miRNAs. By using small RNA sequencing (smRNA-seq, we deciphered the circulating miRNome in the plasma of healthy individual and CAD patients, and found that the plasma miRNA spectrum from CAD patients was significantly different from that of healthy control. Interestingly, smRNA-seq of both healthy and CAD ECFCs showed that twelve miRNAs that had a higher expression in the plasma of CAD patients also showed higher expression in CAD ECFCs when compared with healthy control. This result suggests that these miRNAs may be involved in the regulation of ECFC functions. For identification of potential mRNA targets of the differentially expressed miRNA in CAD patients, cDNA microarray analysis was performed to identify the angiogenesis-related genes that were down-regulated in CAD ECFCs and Pearson's correlation were used to identify miRNAs that were negatively correlated with the identified angiogenesis-related genes. RT-qPCR analysis of the five miRNAs that negatively correlated with the down-regulated angiogenesis-related genes in plasma and ECFC of CAD patients showed miR-146a-5p and miR-146b-5p up

  16. Thioredoxin is involved in endothelial cell extracellular transglutaminase 2 activation mediated by celiac disease patient IgA.

    Directory of Open Access Journals (Sweden)

    Cristina Antonella Nadalutti

    Full Text Available PURPOSE: To investigate the role of thioredoxin (TRX, a novel regulator of extracellular transglutaminase 2 (TG2, in celiac patients IgA (CD IgA mediated TG2 enzymatic activation. METHODS: TG2 enzymatic activity was evaluated in endothelial cells (HUVECs under different experimental conditions by ELISA and Western blotting. Extracellular TG2 expression was studied by ELISA and immunofluorescence. TRX was analysed by Western blotting and ELISA. Serum immunoglobulins class A from healthy subjects (H IgA were used as controls. Extracellular TG2 enzymatic activity was inhibited by R281. PX12, a TRX inhibitor, was also employed in the present study. RESULTS: We have found that in HUVECs CD IgA is able to induce the activation of extracellular TG2 in a dose-dependent manner. Particularly, we noted that the extracellular modulation of TG2 activity mediated by CD IgA occurred only under reducing conditions, also needed to maintain antibody binding. Furthermore, CD IgA-treated HUVECs were characterized by a slightly augmented TG2 surface expression which was independent from extracellular TG2 activation. We also observed that HUVECs cultured in the presence of CD IgA evinced decreased TRX surface expression, coupled with increased secretion of the protein into the culture medium. Intriguingly, inhibition of TRX after CD IgA treatment was able to overcome most of the CD IgA-mediated effects including the TG2 extracellular transamidase activity. CONCLUSIONS: Altogether our findings suggest that in endothelial cells CD IgA mediate the constitutive activation of extracellular TG2 by a mechanism involving the redox sensor protein TRX.

  17. CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    Guillaume Sarrabayrouse

    2014-04-01

    Full Text Available How the microbiota affects health and disease is a crucial question. In mice, gut Clostridium bacteria are potent inducers of colonic interleukin (IL-10-producing Foxp3 regulatory T cells (Treg, which play key roles in the prevention of colitis and in systemic immunity. In humans, although gut microbiota dysbiosis is associated with immune disorders, the underlying mechanism remains unknown. In contrast with mice, the contribution of Foxp3 Treg in colitis prevention has been questioned, suggesting that other compensatory regulatory cells or mechanisms may exist. Here we addressed the regulatory role of the CD4CD8 T cells whose presence had been reported in the intestinal mucosa and blood. Using colonic lamina propria lymphocytes (LPL and peripheral blood lymphocytes (PBL from healthy individuals, and those with colon cancer and irritable bowel disease (IBD, we demonstrated that CD4CD8αα (DP8α T lymphocytes expressed most of the regulatory markers and functions of Foxp3 Treg and secreted IL-10. Strikingly, DP8α LPL and PBL exhibited a highly skewed repertoire toward the recognition of Faecalibacterium prausnitzii, a major Clostridium species of the human gut microbiota, which is decreased in patients with IBD. Furthermore, the frequencies of DP8α PBL and colonic LPL were lower in patients with IBD than in healthy donors and in the healthy mucosa of patients with colon cancer, respectively. Moreover, PBL and LPL from most patients with active IBD failed to respond to F. prausnitzii in contrast to PBL and LPL from patients in remission and/or healthy donors. These data (i uncover a Clostridium-specific IL-10-secreting Treg subset present in the human colonic LP and blood, (ii identify F. prausnitzii as a major inducer of these Treg, (iii argue that these cells contribute to the control or prevention of colitis, opening new diagnostic and therapeutic strategies for IBD, and (iv provide new tools to address the systemic impact of both these Treg

  18. Terapia transfusional en pacientes pediátricos con drepanocitosis Transfusional therapy in pediatric patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Lázaro Cortina Rosales

    2003-12-01

    Full Text Available Se estudiaron 158 niños con drepanocitosis, 114 con anemia drepanocítica (AD, 30 con hemoglobinopatía SC (HSC y 14 con Sb talasemia (Sb Tal. Del total, 134 fueron transfundidos, de estos 108 (94,7 % con AD, 14 con HSC (46,6 % y 12 con Sb Tal (85,6 %. Se agruparon por edades en: menores de 6 años, entre 6 y 12 años y de 13 a 18 años. La transfusión se empleó con mayor frecuencia en los menores de 6 años y sus causas fundamentales fueron: la crisis de secuestro esplénico (CSE, el síndrome torácico agudo (STA y las infecciones; estas causas variaron con la edad. Se realizó exanguinotransfusión en la crisis hepática, en la crisis vaso-oclusiva del sistema nervioso central (CVO del SNC y en el STA. El régimen de hipertransfusión se reservó para las CVO del SNC y las CSE. Las complicaciones detectadas fueron: la reacción febril no hemolítica, la aloinmunización eritrocitaria, la reacción hemolítica y las hepatitis B y C158 children with sickle cell disease, 114 with sickle cell anemia (SCA, 30 with SC haemoglobinopathy (SCH and 14 with Sb thalasemia (Sb Tal., were estudied. Of the total, 134 were transfused, 108 of them (94.7 % with SCA, 14 with SC haemoglobinopathy (SCH (46.6 % and 14 with Sb thalasemia (Sb Tal (85.6 %. They were grouped by age as follows: under 6, betweeen 6 and 12 and from 13 to 18. The transfusion was used more frequently among those under 6 and the main causes were splenic sequestration crisis (SSC, acute thoracic syndrome (ATS and infections. These causes varied according to age. Exanguinotransfusion was performed in the hepatic crisis, in the vasoocclusive crisis of the central nervous system (VOC-CNS and in the ATS. The regimen of hypertransfusion was reserved for the VOC-CNS and SSC. The complications detected were: nonhaemolytic febrile reaction, erythrocytary alloimmunization, haemolytic reaction and hepatitis B and C

  19. Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer – a retrospective analysis: JMTO LC03-02

    Directory of Open Access Journals (Sweden)

    Tada Harue

    2009-08-01

    Full Text Available Abstract Background In Japan, high incidences of interstitial lung disease (ILD and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC. We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients. Findings We obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0–1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7–22.0. ILD developed in 17 patients (3.2%; 95% CI 1.9–5.1%, of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD. Conclusion The results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.

  20. The Injection of Air/Oxygen Bubble into the Anterior Chamber of Rabbits as a Treatment for Hyphema in Patients with Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Emre Ayintap

    2014-01-01

    Full Text Available Purpose. To investigate the changes of partial oxygen pressure (PaO2 in aqueous humour after injecting air or oxygen bubble into the anterior chamber in sickle cell hyphema. Methods. Blood samples were taken from the same patient with sickle cell disease. Thirty-two rabbits were divided into 4 groups. In group 1 (n=8, there was no injection. Only blood injection constituted group 2 (n=8, both blood and air bubble injection constituted group 3 (n=8, and both blood and oxygen bubble injection constituted group 4 (n=8. Results. The PaO2 in the aqueous humour after 10 hours from the injections was 78.45 ± 9.9 mmHg (Mean ± SD for group 1, 73.97 ± 8.86 mmHg for group 2, 123.35 ± 13.6 mmHg for group 3, and 306.47 ± 16.5 mmHg for group 4. There was statistically significant difference between group 1 and group 2, when compared with group 3 and group 4. Conclusions. PaO2 in aqueous humour was increased after injecting air or oxygen bubble into the anterior chamber. We offer to leave an air bubble in the anterior chamber of patients with sickle cell hemoglobinopathies and hyphema undergoing an anterior chamber washout.

  1. Empowering Patients with Chronic Diseases

    DEFF Research Database (Denmark)

    Bestek, Mate; Meglič, Matic; Kurent, Blaž

    2012-01-01

    Background: Chronic diseases require most of the resources in todays healthcare systems. Healthcare systems, as such, are thus not sustainable in the long term. Solutions to this problem are needed and a lot of research is focused on finding new approaches to more sustainable healthcare systems...... himself to become empowered. The patient needs to see data about his health in order to start thinking about new decisions in life that can lead to change in his behaviour. Objective: We have approached the problem of empowering patients with chronic diseases from a biological, psychological, sociological....... We want to develop extensible technology to support even more new interventions for different chronic diseases. We want the technology to enable semantic interoperability with other systems. Methods: We have collaborated with doctors in order to model the care plans for different chronic diseases...

  2. Treatment Of Sickle Cell Disease

    KAUST Repository

    Essack, Magbubah

    2014-12-04

    The present invention includes embodiments for treatment and/or prevention of sickle cell disease that employ Hydroxyfasudil or Isocoronarin D alone or either in conjunction with each other or an inducer of HbF production. The compounds may act synergistically, and the compounds employed circumvent the side effects seen with Hydroxyurea.

  3. Treatment Of Sickle Cell Disease

    KAUST Repository

    Essack, Magbubah; Bajic, Vladimir B.; Radovanovic, Aleksandar

    2014-01-01

    The present invention includes embodiments for treatment and/or prevention of sickle cell disease that employ Hydroxyfasudil or Isocoronarin D alone or either in conjunction with each other or an inducer of HbF production. The compounds may act synergistically, and the compounds employed circumvent the side effects seen with Hydroxyurea.

  4. Protective mechanism against cancer found in progeria patient cells

    Science.gov (United States)

    NCI scientists have studied cells of patients with an extremely rare genetic disease that is characterized by drastic premature aging and discovered a new protective cellular mechanism against cancer. They found that cells from patients with Hutchinson Gi

  5. The effect of angiotensin-2 receptor blocker valsartan on circulating level of endothelial progenitor cells in diabetic patients with asymptomatic coronary artery disease.

    Science.gov (United States)

    Berezin, Alexander E; Kremzer, Alexander A; Martovitskaya, Yulia V; Samura, Tatyana A

    2015-01-01

    Decreased circulating endothelial progenitor cells (EPCs) are considered as strong and robust biomarkers for the prediction of cardiovascular outcomes in diabetic populations. The perspectives for modulating EPCs levels in T2DM with known coronary artery disease (CAD) with different drugs, affected mechanisms of improving mobilization of EPCs from tissue, are not still understood. To evaluate an effect of angiotensin-2 receptor blocker valsartan on circulating level of EPCs in diabetic patients with asymptomatic CAD. The study population was structured retrospectively after determining the CAD by contrast-enhanced spiral computed tomography angiography in 126 asymptomatic subjects. All subjects were distributed into two cohorts depending on daily doses of valsartan given. Low (80-160 mg daily orally) and high doses (240-320 mg daily orally) of valsartan were used and they were adjusted depending on achieving BP level less than 140/80 mmHg. The change from baseline in CD34(+) subset cells (frequencies and absolute values) was not significantly different between treatment cohorts. We found a significant increase of circulating level of CD14(+)CD309(+) cells in two patient cohorts. But more prominent change of CD14(+)CD309(+) cells was verified in subjects who were given valsartan in high daily doses when compared with persons who were included into cohort with low daily doses of the drug (1.96% versus 2.59%, respectively; Pvalsartan only. We found positive influence of angiotensin-2 receptor blocker valsartan in escalation doses on bone marrow-derived EPCs phenotyped as CD14(+)CD309(+) and CD14(+)CD309(+)Tie(2+) in T2DM patients with known asymptomatic CAD. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  6. Antibiotic-Induced Depletion of Anti-inflammatory Clostridia Is Associated with the Development of Graft-versus-Host Disease in Pediatric Stem Cell Transplantation Patients.

    Science.gov (United States)

    Simms-Waldrip, Tiffany R; Sunkersett, Gauri; Coughlin, Laura A; Savani, Milan R; Arana, Carlos; Kim, Jiwoong; Kim, Minsoo; Zhan, Xiaowei; Greenberg, David E; Xie, Yang; Davies, Stella M; Koh, Andrew Y

    2017-05-01

    Adult stem cell transplantation (SCT) patients with graft-versus-host-disease (GVHD) exhibit significant disruptions in gut microbial communities. These changes are associated with higher overall mortality and appear to be driven by specific antibiotic therapies. It is unclear whether pediatric SCT patients who develop GVHD exhibit similar antibiotic-induced gut microbiota community changes. Here, we show that pediatric SCT patients (from Children's Medical Center Dallas, n = 8, and Cincinnati Children's Hospital, n = 7) who developed GVHD showed a significant decline, up to 10-log fold, in gut anti-inflammatory Clostridia (AIC) compared with those without GVHD. In fact, the development of GVHD is significantly associated with this AIC decline and with cumulative antibiotic exposure, particularly antibiotics effective against anaerobic bacteria (P = .003, Firth logistic regression analysis). Using metagenomic shotgun sequencing analysis, we were able to identify specific commensal bacterial species, including AIC, that were significantly depleted in GVHD patients. We then used a preclinical GVHD model to verify our clinical observations. Clindamycin depleted AIC and exacerbated GVHD in mice, whereas oral AIC supplementation increased gut AIC levels and mitigated GVHD in mice. Together, these data suggest that an antibiotic-induced AIC depletion in the gut microbiota is associated with the development of GVHD in pediatric SCT patients. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  7. Alterações hemostáticas em pacientes com doença falciforme Changes in hemostasis in sickle cell disease patients

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    Jaíne B. Stypulkowski

    2010-02-01

    Full Text Available A doença falciforme (DF é uma doença hereditária que tem uma fisiopatologia complexa e diversificada. Além da falcização dos eritrócitos, responsável pelos fenômenos de vaso-oclusão e hemólise, alterações no sistema de coagulação parecem ter papel importante nas várias manifestações clínicas desta doença. Aproximadamente todos os componentes da hemostasia, incluindo função plaquetária, mecanismos procoagulantes, anticoagulantes e sistema fibrinolítico, estão alterados nesta patologia, mesmo em pacientes clinicamente estáveis. A presença da fosfatidilserina (FS na superfície externa da membrana do eritrócito e o aumento dos anticorpos antifosfolipídeos e do fator tecidual (FT marcam o início da ativação da coagulação nestes pacientes. Também a destruição dos eritrócitos diminui a biodisponibilidade do óxido nítrico (NO e, como consequência, modifica a hemostasia vascular, aumentando a ativação plaquetária e a adesão de moléculas ao endotélio. Assim, o objetivo deste trabalho foi abordar as diferentes alterações hemostáticas que ocorrem nos pacientes com doença falciforme, a fim de melhor compreender o estado "hipercoagulável" como é descrito nesta doença.Sickle cell disease is an inherited disease characterized by a complex and varied physiopathology. Apart from the sickle red blood cells, responsible for vascular occlusion and hemolytic anemia, changes in the coagulation system seem to play an important role in the clinical manifestations of this disorder. Nearly every component of hemostasis, including platelet function and the procoagulant, anticoagulant, and fibrinolytic systems, are altered in sickle Cell Disease even in non-crisis steady-state patients. The presence of phosphatidylserine on the external membrane of the red blood cell and the increase in antiphosphatidylserine antibodies and tissue factor mark the beginning of coagulation activation in these patients. Moreover, red

  8. Anemia and hematinic deficiencies in gastric parietal cell antibody-positive and -negative oral mucosal disease patients with microcytosis

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    Hung-Pin Lin

    2017-08-01

    Conclusion: We conclude that GPCA in microcytosis patients' sera may have caused significantly lower mean vitamin B12 level as well as significantly higher mean RDW and serum homocysteine level in our GPCA+/microcytosis patients than in GPCA−/microcytosis patients. Herein, iron deficiency anemia was the most common type of anemia in anemic GPCA+/microcytosis and GPCA−/microcytosis patients.

  9. Pain management trend of vaso-occulsive crisis (VOC) at a community hospital emergency department (ED) for patients with sickle cell disease.

    Science.gov (United States)

    Inoue, Susumu; Khan, Isra'a; Mushtaq, Rao; Sanikommu, Srinivasa Reddy; Mbeumo, Carline; LaChance, Jenny; Roebuck, Michael

    2016-01-01

    Pain management at the emergency department (ED) for vaso-occulsive crisis (VOC) for patients with sickle cell disease has not been optimum, with a long delay in giving the initial analgesic. We conducted a retrospective survey over a 7-year period to determine our ED's timing in giving pain medication to patients with VOC as a quality improvement project. We compared different periods, children vs adults, and the influence of gender in the analgesic administration timing. This is a retrospective chart review of three different periods: (1) years 2007-2008, (2) years 2011-2012, and (3) year 2013. We extracted relevant information from ED records. Data were analyzed using Student t test, chi-square analysis, and the Kruskal-Wallis test. There was a progressive improvement in the time interval to the 1st analgesic over these three periods. Children received analgesics more quickly than adults in all periods. Male adult patients received pain medication faster than female adult patients, although initial pain scores were higher in female than in male patients. Progressively fewer pediatric patients utilized ED over these three periods, but no difference for adult patients was observed. The proportion of pediatric patients admitted to the hospital increased with each period. The progressive decrease in both the number of patients and the number of visits to the ED by children suggested that the collective number of VOC in children has decreased, possibly secondary to the dissemination of hydroxyurea use. We failed to observe the same trend in adult patients. The need for IV access, and ordering laboratory tests or imaging studies tends to delay analgesic administration. Delay in administration of the first analgesic was more pronounced for female adult patients than male adult patients in spite of their higher pain score. Health care providers working in ED should make conscious efforts to respect pain in women as well as pain in men. Though not proven from this study

  10. Genetic engineering with endothelial nitric oxide synthase improves functional properties of endothelial progenitor cells from patients with coronary artery disease: an in vitro study.

    Science.gov (United States)

    Kaur, Savneet; Kumar, T R Santhosh; Uruno, Akira; Sugawara, Akira; Jayakumar, Karunakaran; Kartha, Chandrasekharan Cheranellore

    2009-11-01

    Recent studies have reported a marked impairment in the number and functions of endothelial progenitor cells (EPCs) in patients with coronary artery disease (CAD). In view of an important role of eNOS in angiogenesis, in the present study, we evaluated the effects of eNOS gene transfer in ex vivo expanded EPCs isolated from patients with CAD. The expanded EPCs were transfected with mammalian expression vector pcDNA3.1-eNOS containing the full-length human eNOS gene using lipofectamine. About 35-40% of the eNOS-EPCs had higher expression of eNOS as compared to untransfected EPCs. EPCs transfected with pcDNA3.0-EGFP, the plasmid vector expressing green fluorescent protein (GFP) were used as control. The untransfected, GFP-transfected and eNOS-transfected EPCs were compared in terms of important functional attributes of angiogenesis such as proliferation, migration, differentiation and adhesion/integration into tube-like structures in vitro. Functional studies revealed that in the presence of defined growth conditions, compared to the untransfected and GFP-transfected cells, eNOS-EPCs from patients with CAD have a significant increase in [3H] thymidine-labeled DNA (P < 0.01), migration (14.6 +/- 1.8 and 16.5 +/- 1.9 vs. 23.5 +/- 3.4 cells/field, P < 0.01), ability to differentiate into endothelial-like spindle-shaped cells (46 +/- 4.5 and 56.5 +/- 2.1 vs. 93.2 +/- 6.6 cells/field, P < 0.001) and also incorporation into tube-like structures on the matrigel (GFP-EPCs: 21.25 +/- 2.9 vs. GFP-eNOS-EPCs: 34.5 +/- 5.5 cells/field, P < 0.05). We conclude that eNOS gene transfection is a valuable approach to augment angiogenic properties of ex vivo expanded EPCs and eNOS-modified EPCs may offer significant advantages than EPCs alone in terms of their clinical use in patients with myocardial ischemia.

  11. Direct costs associated with the disease management of patients with unresectable advanced non-small-cell lung cancer in The Netherlands.

    Science.gov (United States)

    Pompen, Marjolein; Gok, Murat; Novák, Annoesjka; van Wuijtswinkel, Rob; Biesma, Bonne; Schramel, Franz; Stigt, Jos; Smit, Hans; Postmus, Pieter

    2009-04-01

    Disease management and costs of treatment of patients with unresectable advanced non-small-cell lung cancer (NSCLC) in The Netherlands are not well known. A retrospective medical chart review was performed by collecting data from the time of diagnosis until the time of death or the end of the evaluation period. In addition to the demographic data, information was collected on the overall management of the patient. Hospital resource utilisation data collected included number of outpatient specialist visits, number and length of hospitalisation, type and number of diagnostic and laboratory procedures, type and number of radiotherapy cycles and detailed information on chemotherapy. To evaluate the economic impact of second-line treatment, a distinction was made between patients who received only best supportive care (BSC, group A) and those who received chemotherapy as a second-line treatment in addition to BSC (group B). The study was performed from the hospital perspective and reports on 2005 costs. Of 102 patients, 74 belonged to group A and 28 to group B. Patient management included a multidisciplinary approach, the extent of which depended on symptoms of the disease and presence of metastases. The average total treatment cost per patient per year of unresectable advanced NSCLC in The Netherlands was euro32,840 in group A and euro31,187 in group B. In both groups, hospitalisation was the major cost driver. In group B second-line chemotherapy was the second largest contributor of the costs. In spite of the difference in numbers of treatment lines provided to patients in groups A and B the total average costs per patient per year were comparable. Overall, the management of unresectable advanced NSCLC appeared to conform with current guidelines in The Netherlands. These patients show high medical resource consumption, with hospitalisation being the main cost driver in both groups. As economic arguments are becoming increasingly important in medical decision making on

  12. Diesel exhaust alters the response of cultured primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD) to non-typeable Haemophilus influenzae.

    Science.gov (United States)

    Zarcone, Maria C; van Schadewijk, Annemarie; Duistermaat, Evert; Hiemstra, Pieter S; Kooter, Ingeborg M

    2017-01-28

    Exacerbations constitute a major cause of morbidity and mortality in patients suffering from chronic obstructive pulmonary disease (COPD). Both bacterial infections, such as those with non-typeable Haemophilus influenzae (NTHi), and exposures to diesel engine emissions are known to contribute to exacerbations in COPD patients. However, the effect of diesel exhaust (DE) exposure on the epithelial response to microbial stimulation is incompletely understood, and possible differences in the response to DE of epithelial cells from COPD patients and controls have not been studied. Primary bronchial epithelial cells (PBEC) were obtained from age-matched COPD patients (n = 7) and controls (n = 5). PBEC were cultured at the air-liquid interface (ALI) to achieve mucociliary differentiation. ALI-PBECs were apically exposed for 1 h to a stream of freshly generated whole DE or air. Exposure was followed by 3 h incubation in presence or absence of UV-inactivated NTHi before analysis of epithelial gene expression. DE alone induced an increase in markers of oxidative stress (HMOX1, 50-100-fold) and of the integrated stress response (CHOP, 1.5-2-fold and GADD34, 1.5-fold) in cells from both COPD patients and controls. Exposure of COPD cultures to DE followed by NTHi caused an additive increase in GADD34 expression (up to 3-fold). Importantly, DE caused an inhibition of the NTHi-induced expression of the antimicrobial peptide S100A7, and of the chaperone protein HSP5A/BiP. Our findings show that DE exposure of differentiated primary airway epithelial cells causes activation of the gene expression of HMOX1 and markers of integrated stress response to a similar extent in cells from COPD donors and controls. Furthermore, DE further increased the NTHi-induced expression of GADD34, indicating a possible enhancement of the integrated stress response. DE reduced the NTHi-induced expression of S100A7. These data suggest that DE exposure may cause adverse health effects in part by

  13. Skeletal MR imaging in sickle cell disease

    International Nuclear Information System (INIS)

    Effmann, E.L.; Kinney, T.R.; Utz, J.A.; Merten, D.F.; Herfkens, R.J.

    1986-01-01

    The authors evaluated eight patients with sickle cell disease (mean age, 15.75 years; range 5-19 years) using MR imaging performed 24-72 hours after hospital admission for crisis. Coronal images of the lower extremities were obtained with a General Electric 1.5-T system and pulse sequences of TR/TE = 500/25 msec and 2,000/40, 80 msec. In three patients a mild decrease in signal intensity was seen on both T1- and T2-weighted images, probably secondary to marrow hyperplasia. In two patients a marked decrease in signal intensity was seen on both T1- and T2-weighted images, probably secondary to the diamagnetic effects of marrow iron. Six patients had bone infarct(s) which appeared as well-defined areas with prolonged T2 relaxation times. MR imaging appears promising for the evaluation of bone marrow in sickle cell anemia

  14. Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial

    Directory of Open Access Journals (Sweden)

    Francine Foss

    2016-03-01

    Full Text Available Abstract Background Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD. Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130, including 15 % with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD. Methods Patients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m2 romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months. Results Of the 32 patients (25 % with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment. The longest SD was >3 years in a patient who received maintenance dosing of 14 mg/m2 on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated. Conclusions We concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses. Trial registration NCT00426764

  15. Isolation of Mycobacterium avium subspecies paratuberculosis Reactive T-cells from Intestinal Biopsies of Crohn's Disease Patients

    Science.gov (United States)

    Crohn’s disease (CD) is a chronic granulomatous inflammation of the intestine. The etiology is still unknown. One hypothesis is that CD is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP) in genetically predisposed individuals. MAP causes a similar disease in ruminants,...

  16. Regulatory T cells and B cells: implication on autoimmune diseases

    OpenAIRE

    Wang, Ping; Zheng, Song Guo

    2013-01-01

    The regulatory T (Treg) cells play an important role in the maintenance of homeostasis and the prevention of autoimmune diseases. Although most studies are focusing on the role of Treg cells in T cells and T cells-mediated diseases, these cells also directly affect B cells and other non-T cells. This manuscript updates the role of Treg cells on the B cells and B cell-mediated diseases. In addition, the mechanisms whereby Treg cells suppress B cell responses have been discussed.

  17. Orbital infarction in sickle cell disease

    International Nuclear Information System (INIS)

    Wolff, M.H.; Sty, J.R.

    1985-01-01

    Bone infarction is common in sickle cell disease; however, involvement of the orbit is not. Only four cases have been reported in the English literature. We describe a patient who presented with headache, proptosis and lid edema due to infarction of the sphenoid bone. The combination of radionuclide bone imaging and computed tomography (CT) of the orbit were useful in differentiating bone infarction from other etiologies of proptosis. (orig.)

  18. The role of a low-dose ketamine-midazolam regimen in the management of severe painful crisis in patients with sickle cell disease.

    Science.gov (United States)

    Tawfic, Qutaiba A; Faris, Ali S; Kausalya, Rajini

    2014-02-01

    Acute pain is one of the main causes of hospital admission in sickle cell disease, with variable intensity and unpredictable onset and duration. We studied the role of a low-dose intravenous (IV) ketamine-midazolam combination in the management of severe painful sickle cell crisis. A retrospective analysis was performed with data from nine adult patients who were admitted to the intensive care unit with severe painful sickle cell crises not responding to high doses of IV morphine and other adjuvant analgesics. A ketamine-midazolam regimen was added to the ongoing opioids as an initial bolus of ketamine 0.25mg/kg, followed by infusion of 0.2-0.25mg/kg/h. A midazolam bolus of 1mg followed by infusion of 0.5-1mg/h was added to reduce ketamine emergence reactions. Reduction in morphine daily requirements and improvement in pain scores were the determinants of ketamine-midazolam effect. The t-tests were used for statistical analysis. Nine patients were assessed, with mean age of 27±11 years. Morphine requirement was significantly lower after adding the IV ketamine-midazolam regimen. The mean±SD IV morphine requirement (milligram/day) in the pre-ketamine day (D0) was 145.6±16.5, and it was 112±12.2 on Day 1 (D1) of ketamine treatment (P=0.007). The Numeric Rating Scale scores on D0 ranged from eight to ten (mean 9.1), but improved to range from five to seven (mean 5.7) on D1. There was a significant improvement in pain scores after adding ketamine-midazolam regimen (P=0.01). Low-dose ketamine-midazolam IV infusion might be effective in reducing pain and opioid requirements in patients with sickle cell disease with severe painful crisis. Further controlled studies are required to prove this effect. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  19. Allogeneic Hematopoietic Stem Cell Transplantation Is an Effective Salvage Therapy for Patients with Chronic Myeloid Leukemia Presenting with Advanced Disease or Failing Treatment with Tyrosine Kinase Inhibitors.

    Science.gov (United States)

    Nair, Anish P; Barnett, Michael J; Broady, Raewyn C; Hogge, Donna E; Song, Kevin W; Toze, Cynthia L; Nantel, Stephen H; Power, Maryse M; Sutherland, Heather J; Nevill, Thomas J; Abou Mourad, Yasser; Narayanan, Sujaatha; Gerrie, Alina S; Forrest, Donna L

    2015-08-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known curative therapy for chronic myeloid leukemia (CML); however, it is rarely utilized given the excellent long-term results with tyrosine kinase inhibitor (TKI) treatment. The purpose of this study is to examine HSCT outcomes for patients with CML who failed TKI therapy or presented in advanced phase and to identify predictors of survival, relapse, and nonrelapse mortality (NRM). Fifty-one patients with CML underwent HSCT for advanced disease at diagnosis (n = 15), TKI resistance as defined by the European LeukemiaNet guidelines (n = 30), TKI intolerance (n = 2), or physician preference (n = 4). At a median follow-up of 71.9 months, the 8-year overall survival (OS), event-free survival (EFS), relapse, and NRM were 68%, 46%, 41%, and 23%, respectively. In univariate analysis, predictors of OS included first chronic phase (CP1) disease status at HSCT (P = .0005), European Society for Blood and Marrow Transplantation score 1 to 4 (P = .04), and complete molecular response (CMR) to HSCT (P treatment to optimize transplantation outcomes. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  20. Ozone exposure is associated with acute changes in inflammation, fibrinolysis, and endothelial cell function in coronary artery disease patients

    Science.gov (United States)

    Background: Air pollution is a major risk factor for cardiovascular disease, of which ozone is a major contributor. Several studies have found associations between ozone and cardiovascular morbidity, but the results have been inconclusive. We investigated associations between oz...

  1. High prevalence of complementary and alternative medicine use among patients with sickle cell disease in a tertiary hospital in Lagos, South West, Nigeria.

    Science.gov (United States)

    Busari, A A; Mufutau, M A

    2017-06-07

    Attention and interest in the use of complementary and alternative medicine (CAM) has been reignited globally, most especially in patients with chronic diseases. Sickle cell disease (SCD) is one of such chronic diseases associated with devastating clinical and psychosocial consequences, thus leading those affected to seek alternative treatment apart from orthodox medicine. Hence, this study aimed to determine the prevalence, pattern and tolerability of the use of CAM in patients with SCD in the Lagos University Teaching Hospital (LUTH). This was a cross-sectional survey of 200 respondents with SCD attending the hematology clinics of the Lagos University Teaching Hospital over a period of 3 months. Data on socio-demographic characteristic, clinical profile, the types and sources of CAM used were collected using a well structured pretested questionnaire. The data obtained were analyzed using Statistical Package for Social Sciences (SPSS®) version 17. Of the 200 patients who participated in the study, 113; 56.5% were males and 87; 43.5% were females. Majority of the SCD patients were 1-10 years old and their mean age was 18.8 ± 14.39 years. CAM was reportedly used by 88.5% of the respondents. Biological (herbal) products 156; 62.9% were the most commonly used CAM, followed by alternative medical systems 52; 20.9% and mind-body interventions 30; 12.1%. Relations, friends and neighbors influenced 85.2% of CAM users by recommending CAM to them. Tolerability of CAM was perceived to be excellent as only 33 (18.6%) of the respondents abandoned the use of CAM. Comparing CAM users and CAM non-users, there was no statistical significant difference in the proportion of those >18 years (45.76% vs 52.17%; p = 0.658), those who experienced two or more crises (51.41% vs 34.78%; p = 0.183), and those with stable haemoglobin concentration of >7 g/dL (15.81% vs 8.69%; p = 0.539) More patients among CAM non-users (91.30%) significantly spend over 3000 Naira (USD 15) per

  2. Patients with Treatment-Requiring Chronic Graft versus Host Disease after Allogeneic Stem Cell Transplantation Have Altered Metabolic Profiles due to the Disease and Immunosuppressive Therapy: Potential Implication for Biomarkers

    Directory of Open Access Journals (Sweden)

    Håkon Reikvam

    2018-01-01

    Full Text Available Chronic graft versus host disease (cGVHD is a common long-term complication after allogeneic hematopoietic stem cell transplantation. The objective of our study was to compare the metabolic profiles for allotransplant recipients and thereby identify metabolic characteristics of patients with treatment-requiring cGVHD. The study included 51 consecutive patients (29 men and 22 women; median age: 44 years, range: 15–66 years transplanted with peripheral blood stem cells derived from human leukocyte antigen-matched family donors. All serum samples investigated by global metabolomic profiling were collected approximately 1 year posttransplant (median 358 days. Thirty-one of the 51 patients (61% had cGVHD 1 year posttransplant. The affected organs were (number of patients liver/bile duct (23, eyes (15, gastrointestinal tract (14, skin (13, mouth (10, lungs (3, and urogenital tract (1. We compared the metabolic profile for patients with and without cGVHD, and a Random Forrest Classification Analysis then resulted in 75% accuracy in differentiating the two groups. The 30 top-ranked metabolites from this comparison included increased levels of bile acids, several metabolites from the cytokine-responsive kynurenine pathway for tryptophan degradation, pro-inflammatory lipid metabolites, phenylalanine and tyrosine metabolites derived from the gut microbial flora, and metabolites reflecting increased oxidative stress. However, nine of these 30 top-ranked metabolites were probably altered due to cyclosporine or steroid treatment, and we therefore did a hierarchical clustering analysis including all 51 patients but only based on the other 21 cGVHD-specific metabolites. This analysis identified three patient subsets: one cluster included mainly patients without cGVHD and had generally low metabolite levels; another cluster included mainly patients with cGVHD (most patients with at least three affected organs and high metabolite levels, and the last

  3. Potential for Monitoring Gut Microbiota for Diagnosing Infections and Graft-versus-Host Disease in Cancer and Stem Cell Transplant Patients.

    Science.gov (United States)

    Koh, Andrew Y

    2017-11-01

    Gut microbiota, the collective community of microorganisms inhabiting the intestine, have been shown to provide many beneficial functions for the host. Recent advances in next-generation sequencing and advanced molecular biology approaches have allowed researchers to identify gut microbiota signatures associated with disease processes and, in some cases, establish causality and elucidate underlying mechanisms. This report reviews 3 commonly used methods for studying the gut microbiota and microbiome (the collective genomes of the gut microorganisms): 16S rRNA gene sequencing, bacterial group or species-specific quantitative polymerase chain reaction (qPCR), and metagenomic shotgun sequencing (MSS). The technical approaches and resources needed for each approach are outlined, and advantages and disadvantages for each approach are summarized. The findings regarding the role of the gut microbiota in the health of patients with cancer and stem cell transplant (SCT) patients (specifically in modulating the development of gut-derived bacterial infections and a posttransplant immune-mediated complication known as graft-vs-host-disease) are reviewed. Finally, there is discussion of the potential viability of these approaches in the actual clinical treatment of cancer and SCT patients. Advances in next-generation sequencing have revolutionized our understanding of the importance of the gut microbiome to human health. Both 16S rRNA gene sequencing and MSS are currently too labor-intensive or computationally burdensome to incorporate into real-time clinical monitoring of gut microbiomes. Yet, the lessons learned from these technologies could be adapted to currently used methods (e.g., qPCR) that could then be rigorously tested in the clinical care of these patients. © 2017 American Association for Clinical Chemistry.

  4. Tibial and fibular angles in homozygous sickle cell disease

    International Nuclear Information System (INIS)

    Akamaguna, A.I.; Odita, J.C.; Ugbodaga, C.I.; Okafor, L.A.

    1986-01-01

    Measurements of the tibial and fibular angles made on ankle radiographs of 34 patients with sickle cell disease were compared with those of 36 normal Nigerians. Widening of the fibular angle, which is an indication of tibiotalar slant, was demonstrated in about 79% of sickle cell disease patients. By using fibular angle measurements as an objective method of assessing subtle tibiotalar slant, it is concluded that the incidence of this deformity is much higher among sickle cell disease patients than previously reported. The mean values of tibial and fibular angles in normal Nigerians are higher than has been reported amongst Caucasians. (orig.)

  5. An Hepatic Abscess in a Patient With Sickle Cell Anemia.

    Science.gov (United States)

    Marolf, Marissa D; Chaudhary, Manu; Kaplan, Sheldon L

    2016-11-01

    We present a case of hepatic abscess in a transfusion-dependent 16-year-old patient with sickle cell disease. There have been 10 such cases in sickle cell disease patients reported, with the last report published greater than a decade ago. The diagnosis of hepatic abscess merits consideration in sickle cell disease patients presenting with fever without a source and/or abdominal pain.

  6. Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.

    Science.gov (United States)

    Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

    2011-08-01

    To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. © 2011 Blackwell Publishing Ltd.

  7. Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease

    Science.gov (United States)

    Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

    2011-01-01

    To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l (95% confidence intervals, −1411, −280 μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. PMID:21592110

  8. Determinants of resting cerebral blood flow in sickle cell disease

    NARCIS (Netherlands)

    Bush, Adam M.; Borzage, Matthew T.; Choi, Soyoung; Václavů, Lena; Tamrazi, Benita; Nederveen, Aart J.; Coates, Thomas D.; Wood, John C.

    2016-01-01

    Stroke is common in children with sickle cell disease and results from an imbalance in oxygen supply and demand. Cerebral blood flow (CBF) is increased in patients with sickle cell disease to compensate for their anemia, but adequacy of their oxygen delivery has not been systematically demonstrated.

  9. New concepts in assessing sickle cell disease severity

    NARCIS (Netherlands)

    Schnog, JJB; Lard, LR; Rojer, RA; Van der Dijs, FPL; Muskiet, FAJ; Duits, AJ

    Vasoocclusion leads to pain, chronic organ damage, and a decreased life expectancy in patients with sickle cell disease. Therapeutic options for sickle cell disease have usually been evaluated according to their capacity for reducing the frequency of vasoocclusive crises requiring clinical

  10. Cost Effectiveness of Screening Patients With Gastroesophageal Reflux Disease for Barrett's Esophagus With a Minimally Invasive Cell Sampling Device

    NARCIS (Netherlands)

    C.R. Heberle (Curtis); Omidvari, A.-H. (Amir-Houshang); A. Ali (Ayman); S. Kroep (Sonja); C.Y. Kong (Chung Yin); J.M. Inadomi (John); J.H. Rubenstein (J.); A.C. Tramontano (Angela C.); Dowling, E.C. (Emily C.); W. Hazelton (William); E.G. Luebeck (E. Georg); I. Lansdorp-Vogelaar (Iris); C. Hur (Chin)

    2017-01-01

    textabstractBackground & Aims It is important to identify patients with Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma (EAC). Patients with BE usually are identified by endoscopy, which is expensive. The Cytosponge, which collects tissue from the esophagus noninvasively, could

  11. Sickle Cell Disease with Cyanotic Congenital Heart Disease: Long-Term Outcomes in 5 Children.

    Science.gov (United States)

    Iannucci, Glen J; Adisa, Olufolake A; Oster, Matthew E; McConnell, Michael; Mahle, William T

    2016-12-01

    Sickle cell disease is a risk factor for cerebrovascular accidents in the pediatric population. This risk is compounded by hypoxemia. Cyanotic congenital heart disease can expose patients to prolonged hypoxemia. To our knowledge, the long-term outcome of patients who have combined sickle cell and cyanotic congenital heart disease has not been reported. We retrospectively reviewed patient records at our institution and identified 5 patients (3 girls and 2 boys) who had both conditions. Their outcomes were uniformly poor: 4 died (age range, 12 mo-17 yr); 3 had documented cerebrovascular accidents; and 3 developed ventricular dysfunction. The surviving patient had developmental delays. On the basis of this series, we suggest mitigating hypoxemia, and thus the risk of stroke, in patients who have sickle cell disease and cyanotic congenital heart disease. Potential therapies include chronic blood transfusions, hydroxyurea, earlier surgical correction to reduce the duration of hypoxemia, and heart or bone marrow transplantation.

  12. Anaesthetic Management of Homozygous Sickle Cell Patients at ...

    African Journals Online (AJOL)

    Background: Sickle cell disease is a common comorbidity in patient presenting for surgical care in our hospitals. The aim of this study was to evaluate the outcome of anaesthetic management of sickle cell disease patients in our hospital. Patients and method: A prospective audit was conducted for a period of 12 months, ...

  13. [Skin biopsy in diagnosis of chronic graft-versus-host disease in patients after allogeneic haematopoietic stem cell transplantation: pathologist's point of view on quantitative scoring system].

    Science.gov (United States)

    Grzanka, Dariusz; Styczyński, Jan; Debski, Robert; Krenska, Anna; Pacholska, Małgorzata; Prokurat, Andrzej I; Wysocki, Mariusz; Marszałek, Andrzej

    2008-01-01

    Pathology diagnosis of chronic graft-versus-host-disease (GVHD) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) is an important issue in clinical follow-up, in spite of frequent difficulties in interpretation., related to dynamic changes occurring in the skin during the disease, as well as to sequelae of basic disease and immunosuppressive therapy. Recently presented Consensus NIH (National Health Institute, Bethesda, USA) of histopathologic (HP) analysis is still complex and intrinsically divergent, thus clinically difficult to implement. Analysis of clinical value of histological evaluation results of skin biopsy in children after allo-HSCT and its correlation with clinical status. Ten skin biopsies were taken from 7 patients (4 boys, 3 girls, age 3-15 years) after allo-HSCT (6 MFD, 1 MMUD) and analyzed after hematoxylin/eosine and immunohistochemical (CD3, CD45T, CD20) staining. Pathology analysis was based on commonly accepted criteria enabling simple and unambiguous interpretation. Results were compared with clinical data and indications for immunosuppressive therapy. It was found that reliable and coherent interpretation can be made when following parameters were taken into account: 1. in epithelium: the presence of apoptosis, archetypical changes and vacuolar degeneration in the basilar layer, presence of CD3/CD45 in the epidermis; 2. in the dermis: the extent of collagenization, presence of melanophages and lymphocyte infiltrations; 3. in the eccrine glands epithelium: eccrine glands atrophy and presence of lymphocytes. A new scoring system of skin biopsy analysis in patients with chronic GVHD based on the modified NIH Consensus was proposed. The preliminary clinical value of histological results was assessed. Skin biopsy evaluation based on limited qualitative and quantitative analysis of lymphocyte infiltrates together with studies on intensity of apoptosis, collagenization and archetypical changes is a valuable diagnostic method

  14. Management of the acute painful crisis in sickle cell disease- a re-evaluation of the use of opioids in adult patients.

    Science.gov (United States)

    Telfer, Paul; Bahal, Nawal; Lo, Alice; Challands, Joanne

    2014-07-01

    Management of the acute painful crisis (APC) of sickle cell disease (SCD) remains unsatisfactory despite advances in the understanding and management of acute pain in other clinical settings. One reason for this is an unsophisticated approach to the use of opioid analgesics for pain management. This applies to haematologists who are responsible for developing acute sickle pain management protocols for their patients, and to health care staff in the acute care setting. The objective of this article is to evaluate the evidence for use of opioids in APC management. We have highlighted the possibilities for improving management by using alternatives to morphine, and intranasal (IN) or transmucosal routes of administration for rapid onset of analgesia in the emergency department (ED). We suggest how experience gained in managing acute sickle pain in children could be extrapolated to adolescents and young adults. We have also questioned whether patients given strong opioids in the acute setting are being safely monitored and what resources are required to ensure efficacy, safety and patient satisfaction. We also identify aspects of care where there are significant differences of opinion, which require further study by randomized controlled trial. © 2014 John Wiley & Sons Ltd.

  15. Asthma in Sickle Cell Disease: Implications for Treatment

    Directory of Open Access Journals (Sweden)

    Kathryn Blake

    2011-01-01

    Full Text Available Objective. To review issues related to asthma in sickle cell disease and management strategies. Data Source. A systematic review of pertinent original research publications, reviews, and editorials was undertaken using MEDLlNE, the Cochrane Library databases, and CINAHL from 1947 to November 2010. Search terms were [asthma] and [sickle cell disease]. Additional publications considered relevant to the sickle cell disease population of patients were identified; search terms included [sickle cell disease] combined with [acetaminophen], [pain medications], [vitamin D], [beta agonists], [exhaled nitric oxide], and [corticosteroids]. Results. The reported prevalence of asthma in children with sickle cell disease varies from 2% to approximately 50%. Having asthma increases the risk for developing acute chest syndrome , death, or painful episodes compared to having sickle cell disease without asthma. Asthma and sickle cell may be linked by impaired nitric oxide regulation, excessive production of leukotrienes, insufficient levels of Vitamin D, and exposure to acetaminophen in early life. Treatment of sickle cell patients includes using commonly prescribed asthma medications; specific considerations are suggested to ensure safety in the sickle cell population. Conclusion. Prospective controlled trials of drug treatment for asthma in patients who have both sickle cell disease and asthma are urgently needed.

  16. CD4 T Cells From Intestinal Biopsies of Crohn's Disease Patients React to Mycobacterium avium subspecies paratuberculosis

    Science.gov (United States)

    The role of Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn’s disease (CD) remains controversial. One issue that has been raised is the lack of data showing a cellular immune response to MAP. Earlier studies have mostly focused on responses in peripheral blood which have several limit...

  17. Inflammatory Stress on Autophagy in Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease during 24 Months of Follow-Up.

    Directory of Open Access Journals (Sweden)

    Arnaud François

    Full Text Available Recent findings indicate that microglia in Alzheimer's disease (AD is senescent whereas peripheral blood mononuclear cells (PBMCs could infiltrate the brain to phagocyte amyloid deposits. However, the molecular mechanisms involved in the amyloid peptide clearance remain unknown. Autophagy is a physiological degradation of proteins and organelles and can be controlled by pro-inflammatory cytokines. The purpose of this study was to evaluate the impact of inflammation on autophagy in PBMCs from AD patients at baseline, 12 and 24 months of follow-up. Furthermore, PBMCs from healthy patients were also included and treated with 20 μM amyloid peptide 1-42 to mimic AD environment. For each patient, PBMCs were stimulated with the mitogenic factor, phytohaemagglutin (PHA, and treated with either 1 μM C16 as an anti-inflammatory drug or its vehicle. Autophagic markers (Beclin-1, p62/sequestosome 1 and microtubule-associated protein-light chain 3: LC3 were quantified by western blot and cytokines (Interleukin (IL-1β, Tumor necrosis Factor (TNF-α and IL-6 by Luminex X-MAP® technology. Beclin-1 and TNF-α levels were inversely correlated in AD PBMCs at 12 months post-inclusion. In addition, Beclin-1 and p62 increased in the low inflammatory environment induced by C16. Only LC3-I levels were inversely correlated with cognitive decline at baseline. For the first time, this study describes longitudinal changes in autophagic markers in PBMCs of AD patients under an inflammatory environment. Inflammation would induce autophagy in the PBMCs of AD patients while an anti-inflammatory environment could inhibit their autophagic response. However, this positive response could be altered in a highly aggressive environment.

  18. Presence of pain on three or more days of the week is associated with worse patient reported outcomes in adults with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Bakshi N

    2018-02-01

    Full Text Available Nitya Bakshi,1,2 Diana Ross,1 Lakshmanan Krishnamurti1,2 1Division of Pediatric Hematology-Oncology-BMT, Department of Pediatrics, Emory University, Atlanta, GA, USA; 2Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA, USA Abstract: While acute episodic pain is the hallmark of sickle cell disease (SCD, transition to chronic pain is a major cause of morbidity and impaired quality of life. One of the core diagnostic criteria used by Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy (AAPT to define chronic SCD pain is the presence of pain on a “majority of days” in the past 6 months in one or more locations. The frequency characteristic of “majority of days” is adapted from the criteria of 15 days or more per month, used to define chronic migraine, but there are inadequate data to support this cutoff in SCD. Using an existing dataset of adults with SCD who completed patient-reported outcomes of pain interference, physical functioning, anxiety, depression, and fatigue using the National Institutes of Health (NIH patient-reported outcomes measures information system (PROMIS short-form instruments, we examined the association of the presence of pain on 3 or more days per week with patient-reported outcomes of functioning. In unadjusted analyses, presence of pain on 3 or more days a week was associated with higher median PROMIS scores of pain interference, anxiety, and depression. Median PROMIS scores of fatigue and physical function were worse in women compared with men in unadjusted analyses. We did not find any difference in median PROMIS pain scores between adults aged ≤35 years compared with those aged ≥35 years. In linear regression models, after adjustment for age and sex, the presence of pain on 3 or more days a week was found to be associated with worse pain interference and anxiety. These data support

  19. Comparison of Two Different Methods of Stem Cell Therapy of Critical Limb Ischemia in Patients with Diabetic Foot Disease

    Czech Academy of Sciences Publication Activity Database

    Dubský, M.; Jirkovská, A.; Bém, R.; Pagacová, L.; Fejfarová, V.; Varga, M.; Skibová, J.; Langkramer, S.; Lesný, Petr; Syková, Eva

    2010-01-01

    Roč. 59, Suppl.1 (2010), A323-A324 ISSN 0012-1797. [Annual Meeting of the American Diabetes Association /70./. 25.07.2010-29.07.2010, Orlando ] Institutional research plan: CEZ:AV0Z50390703 Keywords : stem cell * endocrinology Subject RIV: FH - Neurology

  20. Determination of the best method to estimate glomerular filtration rate from serum creatinine in adult patients with sickle cell disease: a prospective observational cohort study

    Directory of Open Access Journals (Sweden)

    Arlet Jean-Benoît

    2012-08-01

    Full Text Available Abstract Background Sickle cell disease (SCD leads to tissue hypoxia resulting in chronic organ dysfunction including SCD associated nephropathy. The goal of our study was to determine the best equation to estimate glomerular filtration rate (GFR in SCD adult patients. Methods We conducted a prospective observational cohort study. Since 2007, all adult SCD patients in steady state, followed in two medical departments, have had their GFR measured using iohexol plasma clearance (gold standard. The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD-EPI equations without adjustment for ethnicity were tested to estimate GFR from serum creatinine. Estimated GFRs were compared to measured GFRs according to the graphical Bland and Altman method. Results Sixty-four SCD patients (16 men, median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They were Sub-Saharan Africa and French West Indies natives and predominantly lean (median body mass index: 22 kg/m2 [16-33]. Hyperfiltration (defined as measured GFR >110 mL/min/1.73 m2 was detected in 53.1% of patients. Urinary albumin/creatinine ratio was higher in patients with hyperfiltration than in patients with normal GFR (4.05 mg/mmol [0.14-60] versus 0.4 mg/mmol [0.7-81], p = 0.01. The CKD-EPI equation without adjustment for ethnicity had both the lowest bias and the greatest precision. Differences between estimated GFRs using the CKP-EPI equation and measured GFRs decreased with increasing GFR values, whereas it increased with the Cockcroft-Gault and MDRD-v4 equations. Conclusions We confirm that SCD patients have a high rate of glomerular hyperfiltration, which is frequently associated with microalbuminuria or macroalbuminuria. In non-Afro-American SCD patients, the best method for estimating GFR from serum creatinine is the CKD-EPI equation without adjustment for ethnicity. This equation is particularly accurate to estimate high GFR values, including glomerular

  1. Evaluation of high performance liquid chromatography (HPLC) pattern and prevalence of beta-thalassaemia trait among sickle cell disease patients in Lagos, Nigeria.

    Science.gov (United States)

    Adeyemo, Titilope; Ojewunmi, Oyesola; Oyetunji, Ajoke

    2014-01-01

    Sickle cell disease (SCD) is the most common inherited disorder of haemoglobin worldwide. This study evaluated the chromatographic patterns and red blood cell indices of sickle cell patients to determine the co-inheritance of other haemoglobin(Hb) variants and β-thalassaemia trait. Red cell indices, blood film, sickle solubility test, Hb electrophoresis using alkaline cellulose acetate membrane, and chromatographic patterns using Bio Rad HPLC Variant II were evaluated for 180 subjects. Based on low MCV 4.0% on HPLC and Hb variants eluting outside the S and C windows, at least four haemoglobin phenotypes (SS: 87.7%; SC: 1.1%; SD Punjab: 0.6%; Sβ-thalassemia: 10.6%) were identified. Mean Hb F% was 8.1±5.1 (median 7.65) for Hb SS and 6.03±5.2 (median 3.9) for Hb Sβ-thalassemia trait. Majority of Hb SS (69.1%) had Hb F% less than 10 while 27.6% had 10-19.9 and 3.2% had ≥ 20. Mean Hb F% was higher in female Hb SS (9.55±5.09; mean age 7.4±3.8 years) than the males (7.63±4.80; mean age 6.9±3.8 years) (P=0.02). A borderline significant negative correlation between age and Hb F levels among Hb SS subjects (r= -0.169 P=0.038) was also observed. Our data suggests that α and β- thalassaemia traits, and other haemoglobin variants co-exist frequently with SCD in our population.

  2. A randomized trial of artesunate-amodiaquine versus artemether-lumefantrine in Ghanaian paediatric sickle cell and non-sickle cell disease patients with acute uncomplicated malaria

    DEFF Research Database (Denmark)

    Adjei, George O; Goka, Bamenla Q; Enweronu-Laryea, Christabel C

    2014-01-01

    of the SCD patients were also compared with a group of malaria-negative SCD children (n = 82) in steady state. RESULTS: The parasite densities on admission were significantly lower in the SCD group, compared with the non-SCD group (p = 0.0006). The parasite reduction ratio (PRR) was lower, clearance....../57) in the SCD group and 96.4% (53/55) in the non-SCD group. The fractional changes in haemoglobin, platelets and white blood cell counts between baseline (day 0) and endpoint (day 42) were 16.9, 40.6 and 92.3%, respectively, for the SCD group, and, 12.3, 48.8 and 7.5%, respectively, for the non-SCD group....... There were no differences in these indices between AA- and AL-treated subjects. CONCLUSIONS: The parasite clearance of SCD children with uncomplicated malaria was slower compared with non-SCD children. AA and AL showed similar clinical and parasitological effects in the SCD and non-SCD groups...

  3. Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients

    Directory of Open Access Journals (Sweden)

    Ekaterina A. Semenova

    2016-07-01

    Full Text Available Small cell lung cancer (SCLC is an aggressive neuroendocrine tumor, and no effective treatment is available to date. Mouse models of SCLC based on the inactivation of Rb1 and Trp53 show frequent amplifications of the Nfib and Mycl genes. Here, we report that, although overexpression of either transcription factor accelerates tumor growth, NFIB specifically promotes metastatic spread. High NFIB levels are associated with expansive growth of a poorly differentiated and almost exclusively E-cadherin (CDH1-negative invasive tumor cell population. Consistent with the mouse data, we find that NFIB is overexpressed in almost all tested human metastatic high-grade neuroendocrine lung tumors, warranting further assessment of NFIB as a tumor progression marker in a clinical setting.

  4. Improving Cultural Competency and Disease Awareness among Oncology Nurses Caring for Adult T-Cell Leukemia and Lymphoma Patients

    Science.gov (United States)

    Cortese-Peske, Marisa A.

    2013-01-01

    Foreign-born residents face significant challenges accessing and receiving quality healthcare in the U.S. These obstacles include a lack of information on how to access care, fear, as well as communication and cultural barriers (Portes, Fernandez-Kelly & Light, 2012). Increasing healthcare providers' knowledge regarding a patient's…

  5. the orthodontic management of an adult with sickle cell disease

    African Journals Online (AJOL)

    2015-09-01

    Sep 1, 2015 ... a patient with Sickle Cell Disease (SCD) needs ortho- dontic treatment ... Orthodontic Management. 215. Measures ... under strict control by the Dental Hygienists to avoid ... Ghana. Pediatrics 2008; 121 (suppl 2): 120-121. 2.

  6. Genome engineering of stem cell organoids for disease modeling.

    Science.gov (United States)

    Sun, Yingmin; Ding, Qiurong

    2017-05-01

    Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized disease information and recapitulate disease development processes at the molecular, cellular and organ levels. With recent development in stem cell field, a variety of tissue organoids can be derived from patient specific pluripotent stem cells and adult stem cells. In combination with the state-of-the-art genome editing tools, organoids can be further engineered to mimic disease-relevant genetic and epigenetic status of a patient. This has therefore enabled a rapid expansion of sophisticated in vitro disease models, offering a unique system for fundamental and biomedical research as well as the development of personalized medicine. Here we summarize some of the latest advances and future perspectives in engineering stem cell organoids for human disease modeling.

  7. Cerebrovascular disease in pediatric patients

    Directory of Open Access Journals (Sweden)

    Rotta Newra Tellechea

    2002-01-01

    Full Text Available Although rare in childhood, stroke may have a serious impact when it happens in this stage of life. Also, it may be the first sign of a systemic disease. We report 12 cases of patients with stroke treated in the Neuropediatrics Unit of Hospital de Clínicas de Porto Alegre (HCPA from March 1997 to March 2000. All patients, from term infants to 12-year-old children hospitalized in the Pediatrics Unit of HCPA, had clinical suspicion of stroke, which was later confirmed by radiological studies. Patient follow up ranged from 1 to 6 years (mean = 3.4 years. Presenting symptoms were hemiparesis in 9 patients, seizures in 7, deviation of labial commissure in 3, and loss of consciousness in 1. The increase in the number of cases of childhood stroke identified and later confirmed by noninvasive methods had helped in the determination of different ethiologies of stroke: the most frequent being hematologic, cardiac and genetic diseases. However, our study included 6 newborns with stroke whose ethiology was not identified. Seven children with seizures received phenobarbital. Six term infants had neonatal seizures secondary to stroke and restricted to the first 72 hours of life.

  8. Stem cell therapy for inflammatory bowel disease

    NARCIS (Netherlands)

    Duijvestein, Marjolijn

    2012-01-01

    Hematopoietic stem cell transplantation (HSCT) and mesenchymal stromal (MSC) cell therapy are currently under investigation as novel therapies for inflammatory bowel diseases (IBD). Hematopoietic stem cells are thought to repopulate the immune system and reset the immunological response to luminal

  9. Prevention of Epstein-Barr virus-lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation

    NARCIS (Netherlands)

    J.W.J. van Esser (Joost); H.G.M. Niesters (Bert); B. van der Holt (Bronno); E. Meijer (Ellen); A.D.M.E. Osterhaus (Albert); J.W. Gratama (Jan-Willem); L.F. Verdonck (Leo); B. Löwenberg (Bob); J.J. Cornelissen (Jan)

    2002-01-01

    textabstractRecipients of a partially T-cell-depleted (TCD) allogeneic stem cell transplantation (allo-SCT) developing reactivation of Epstein-Barr virus (EBV) with quantified viral DNA levels exceeding 1000 genome equivalents/milliliter (geq/mL) are at high risk for EBV-lymphoproliferative disease

  10. Rituximab therapy in a patient with low grade B-cell lymphoproliferative disease and concomitant acquired angioedema

    Directory of Open Access Journals (Sweden)

    Kaur R

    2014-12-01

    Full Text Available Ravdeep Kaur, Aerik Anthony Williams, Catherine Baker Swift, Jason W Caldwell Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, NC, USA Abstract: Acquired angioedema is often associated with significant morbidity. An underlying lymphatic malignancy, autoimmune disorder, adenocarcinoma, or other malignancy may be present. Screening for these disorders should occur in all patients with acquired angioedema as treatment may result in resolution of angioedema. Keywords: complement, C1-INH deficiency, ecallantide, hemopathy

  11. CD4+, CD8+, CD3+ cell counts and CD4+/CD8+ ratio among patients with mycobacterial diseases (leprosy, tuberculosis), HIV infections, and normal healthy adults: a comparative analysis of studies in different regions of India.

    Science.gov (United States)

    Hussain, Tahziba; Kulshreshtha, K K; Yadav, V S; Katoch, Kiran

    2015-01-01

    In this study, we estimated the CD4+, CD8+, CD3+ cell counts and the CD4/CD8 ratio among normal healthy controls (adults and children), leprosy patients (without any complications and during reactional states), TB patients (with and without HIV), and HIV-positive patients (early infection and full-blown AIDS) and correlated the changes with disease progression. In our study, it was observed that among adults, CD4+ cell counts ranged from 518-1098, CD8+ from 312-952, whereas CD4/CD8 ratio from 0.75-2.30. Among children, both CD4+ and CD8+ cells were more and the CD4/CD8 ratio varied from 0.91-3.17. With regard to leprosy patients, we observed that CD4+ and CD8+ cell counts were lower among PB (pauci-bacillary) and MB (multi-bacillary) patients. CD4/CD8 ratio was 0.99 ± 0.28 among PB patients while the ratio was lower, 0.78 ± 0.20, among MB patients. CD4+ cell counts were raised during RR (reversal reactions) and ENL (erythema nodosum leprosum) among the PB and MB patients whereas the CD8+ cell counts were lower among PB and MB patients. CD4/CD8 ratio doubled during reactional episodes of RR and ENL. Among the HIV-negative tuberculosis (TB) patients, both the CD4+ and CD8+ cell counts were found to be less and the CD4/CD8 ratio varied between 0.53-1.75. Among the HIV-positive TB patients and HIV-positive patients, both the CD4+ and CD8+ cells were very less and ratio drops significantly. In the initial stages of infection, as CD4+ counts drop, an increase in the CD8+ cell counts was observed and the ratio declines. In full-blown cases, CD4+ cell counts were very low, 3-4 to 54 cells, CD8+ cells from 12-211 and the ratio drops too low. This study is the first of its kind in this region of the country and assumes importance since no other study has reported the values of CD4+ and CD8+ T-lymphocyte counts among patients with mycobacterial diseases (leprosy and TB), HIV infections along with normal healthy individuals of the region, and correlation with clinical

  12. Plasma stromal cell-derived factor 1α/CXCL12 level predicts long-term adverse cardiovascular outcomes in patients with coronary artery disease.

    Science.gov (United States)

    Ghasemzadeh, Nima; Hritani, Abdul Wahab; De Staercke, Christine; Eapen, Danny J; Veledar, Emir; Al Kassem, Hatem; Khayata, Mohamed; Zafari, A Maziar; Sperling, Laurence; Hooper, Craig; Vaccarino, Viola; Mavromatis, Kreton; Quyyumi, Arshed A

    2015-01-01

    Stromal derived factor-1α/CXCL12 is a chemoattractant responsible for homing of progenitor cells to ischemic tissues. We aimed to investigate the association of plasma CXCL12 with long-term cardiovascular outcomes in patients with coronary artery disease (CAD). 785 patients aged: 63 ± 12 undergoing coronary angiography were independently enrolled into discovery (N = 186) and replication (N = 599) cohorts. Baseline levels of plasma CXCL12 were measured using Quantikine CXCL12 ELISA assay (R&D systems). Patients were followed for cardiovascular death and/or myocardial infarction (MI) for a mean of 2.6 yrs. Cox proportional hazard was used to determine independent predictors of cardiovascular death/MI. The incidence of cardiovascular death/MI was 13% (N = 99). High CXCL12 level based on best discriminatory threshold derived from the ROC analysis predicted risk of cardiovascular death/MI (HR = 4.81, p = 1 × 10(-6)) independent of traditional risk factors in the pooled cohort. Addition of CXCL12 to a baseline model was associated with a significant improvement in c-statistic (AUC: 0.67-0.73, p = 0.03). Addition of CXCL12 was associated with correct risk reclassification of 40% of events and 10.5% of non-events. Similarly for the outcome of cardiovascular death, the addition of the CXCL12 to the baseline model was associated with correct reclassification of 20.7% of events and 9% of non-events. These results were replicated in two independent cohorts. Plasma CXCL12 level is a strong independent predictor of adverse cardiovascular outcomes in patients with CAD and improves risk reclassification. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Real-life experience with hydroxyurea in sickle cell disease: A multicenter study in a cohort of patients with heterogeneous descent.

    Science.gov (United States)

    Rigano, Paolo; De Franceschi, Lucia; Sainati, Laura; Piga, Antonio; Piel, Frédéric B; Cappellini, Maria Domenica; Fidone, Carmelo; Masera, Nicoletta; Palazzi, Giovanni; Gianesin, Barbara; Forni, Gian Luca

    2018-03-01

    We conducted the first nation-wide cohort study of sickle cell disease (SCD) in Italy, a Southern European country exposed to intense recent flux migration from endemic areas for SCD. We evaluate the impact of hydroxyurea on a total of 652 pediatric and adult patients from 33 Reference Centers for SCD (mean age 24.5±15years, 51.4% males). Hydroxyurea median treatment duration was 7years (range: crisis (-34.1%, p<0.001), hospitalization (-53.2%, p<0.001), and bone necrosis (-6.9%, p<0.001). New silent cerebral infarction (SCI) occurred during treatment (+42.4%, p<0.001) but not stroke (+0.5%, p=0.572). These observations were generally consistent upon stratification for age, descent (Caucasian or African), genotype (βS/βS, βS/β 0 or βS/β + ) and duration of treatment (< or ≥10years). There were no new safety concerns observed compared to those commonly reported in the literature. Our study, conducted on a large population of patients with different descent and compound state supports the benefits of hydroxyurea therapy as a treatment option. Registered at clinical trials.gov (NCT02709681). Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Sortilin-Related Receptor Expression in Human Neural Stem Cells Derived from Alzheimer’s Disease Patients Carrying the APOE Epsilon 4 Allele

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    Alen Zollo

    2017-01-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4 allele. Changes in amyloid precursor protein (APP binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1 as an important factor in APP trafficking and processing. Recent in vitro evidence has associated the APOE4 allele and alterations in the SORL1 pathway with AD development and progression. Here, we analyzed SORL1 expression in neural stem cells (NSCs from AD patients carrying null, one, or two copies of the APOE4 allele. We show reduced SORL1 expression only in NSCs of a patient carrying two copies of APOE4 allele with increased Aβ/SORL1 localization along the degenerated neurites. Interestingly, SORL1 binding to APP was largely compromised; this could be almost completely reversed by γ-secretase (but not β-secretase inhibitor treatment. These findings may yield new insights into the complex interplay of SORL1 and AD pathology and point to NSCs as a valuable tool to address unsolved AD-related questions in vitro.

  15. The super sickling haemoglobin HbS-Oman: a study of red cell sickling, K+ permeability and associations with disease severity in patients heterozygous for HbA and HbS-Oman (HbA/S-Oman genotype).

    Science.gov (United States)

    Al Balushi, Halima W M; Wali, Yasser; Al Awadi, Maha; Al-Subhi, Taimoora; Rees, David C; Brewin, John N; Hannemann, Anke; Gibson, John S

    2017-10-01

    Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K + permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S-Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K + was markedly abnormal with elevated activities of P sickle , Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca 2+ entry and Mg 2+ loss via P sickle stimulating Gardos channel and KCC activities. The abnormal red cell behaviour was similar to that in the commonest genotype of SCD, HbSS, in which the level of mutated Hb is considerably higher. Although activities of all three K + transporters also correlated with the level of HbS-Oman, there was no association between transport phenotype and disease severity. The super sickling behaviour of HbS-Oman may obviate the need for solute loss and red cell dehydration to encourage Hb polymerisation, required in other SCD genotypes. Disease severity was reduced by concurrent α thalassaemia, as observed in other SCD genotypes, and represents an obvious genetic marker for prognostic tests of severity in young SCD patients of the HbA/S-Oman genotype. © 2017 John Wiley & Sons Ltd.

  16. Cytometric evaluation of intracellular IFN-γ and IL-4 levels in thyroid follicular cells from patients with autoimmune thyroid diseases

    Directory of Open Access Journals (Sweden)

    Bossowski Artur

    2011-09-01

    Full Text Available Abstract Background In recent few years is underlined that altered balance of pro- and anti-inflammatory cytokines play an important role in the pathogenesis of AITD. The aim of this study was to estimate intracellular INF-γ and IL-4 levels in thyroid-infiltrating lymphocytes and thyrocytes isolated from thyroid tissues in 54 adolescent patients aged 8-21 years, with Graves' disease (GD; n = 18, Hashimoto's thyroiditis (HT; n = 18 and non-toxic multinodular goiter (NTMG; n = 18. Methods Fresh thyroid tissues were taken on culture medium RPMI -1640, it was mechanically prepared. In next step were added cell activators -12- myristate 13- the acetate (PMA and Ionomycin as well as the inhibitor of transportation of proteins - Breferdin A. They were cultured 24 hours in 50 ml flasks at 37°C in a 5-95% CO2-air water-saturated atmosphere. After that, thyrocytes were identified by mouse mAb directed against human TPO epitope 64 conjugated with rabbit anti-mouse antibodies IgG (Fab'2 labeled by FITC. After incubation at room temperature to each of samples added reagent A fixative the cellular membrane. In next step into the cell suspensions were added reagent B to permeabilization of cellular membrane and specific anti-IL-4-PE or anti-IFN-γ-PE mAbs. Identification of intracellular cytokines in T lymphocytes was performed in the same procedure with application of anti-CD4-PerCP and anti-CD8-PerCP mAbs specific for T lymphocytes. The cells were analyzed in a flow cytometry (Coulter EPICS XL. Results In examined group of patients with GD we observed statistically significant higher mean percentage of cells with phenotype CD4+IL-4 (p Conclusions We conclude that human thyrocytes in autoimmune thyroid disorders could be a source of cytokine production and that their activation influences local interaction with T lymphocytes inflowing to the thyroid gland.

  17. High plasma homocyst(e)ine levels in elderly Japanese patients are associated with increased cardiovascular disease risk independently from markers of coagulation activation and endothelial cell damage.

    Science.gov (United States)

    Kario, K; Duell, P B; Matsuo, T; Sakata, T; Kato, H; Shimada, K; Miyata, T

    2001-08-01

    Elevated plasma homocyst(e)ine is a risk factor for cardiovascular disease (CVD) in many populations, but the relationship between homocyst(e)ine and CVD in Japanese subjects has been unclear. It has been hypothesized that the link between homocyst(e)ine and CVD may be mediated in part by activation of coagulation and endothelial cell injury in the elderly Japanese subjects. To further evaluate this hypothesis, the present cross-sectional study was designed to assess the relationships among plasma homocyst(e)ine concentrations, risk of CVD, and markers of coagulation (fibrinogen, FVII, F1+2, FVIIa and FXIIa) and endothelial cell damage (vWF and thrombomodulin) in 146 elderly Japanese subjects (79 healthy controls and 67 patients with CVD). The geometric mean (range) of plasma homocyst(e)ine concentrations was 10.2 (3.2--33) micromol/l in 79 Japanese healthy elderly subjects. As expected, healthy female and male elderly subjects had homocyst(e)ine levels that were 2.5 and 5.3 micromol/; higher, respectively, compared to healthy young control subjects (n=62). Healthy young and elderly men had homocyst(e)ine levels that were 1.7 and 4.5 micromol/l higher, respectively, compared to values in women. This higher plasma homocyst(e)ine levels in the elderly subjects were negatively correlated with levels of folic acid, albumin and total cholesterol, but were not significantly related to markers of coagulation or endothelial cell-damage. The results of multiple logistic regression analyses suggested that high homocyst(e)ine levels were independently related to CVD risk. In addition, levels of FVIIa, and F1+2 were significantly higher in elderly Japanese patients with CVD compared to elderly subjects without CVD, but were unrelated to plasma homocyst(e)ine concentrations. In summary, elevated plasma concentrations of homocyst(e)ine, FVIIa, and F1+2 were associated with increased risk of CVD in elderly male and female Japanese subjects, but the association between homocyst

  18. Acute clinical events in patients with sickle cell disease: epidemiology and treatment Eventos agudos em doença falciforme: epidemiologia e tratamento

    Directory of Open Access Journals (Sweden)

    Monique M. Loureiro

    2008-04-01

    Full Text Available Sickle cell disease is a hereditary illness of high prevalence in black population, and involved patients frequently have multiple hospitalizations. Our objective was to describe and to analyze the clinical course of hospitalizations in patients with sickle cell disease. Cross-sectional study of 78 patients submitted to 230 hospital admissions due to acute complications of sickle cell disease, from 2000 to 2004 in a public teaching hospital in Rio de Janeiro city, RJ, Brazil. Outcomes variables were length of hospital stay and death. Main covariables were age, gender, chronic renal failure, causes of hospitalization and use of medicines. Proportions were compared using the chi-square or the Fischer test, and for the continuous variables, Mann-Whitney test was used. The median age in years was 20.3 (15-53 and the most frequent clinical event was acute painful episode (73.5%. Mean length of stay was significantly higher in admissions caused by different reasons than acute painful episode (p A doença falciforme é uma doença hereditária, de alta prevalência na população negra, que leva a múltiplas internações hospitalares. Nosso objetivo foi descrever e analisar o curso clínico de pacientes com doença falciforme hospitalizados.Realizou-se estudo transversal de 78 pacientes submetidos a 230 internações hospitalares devido a complicações agudas da doença falciforme, de 2000 a 2004, em um hospital universitário no Rio de Janeiro-RJ, Brasil. Os desfechos estudados foram tempo de permanência hospitalar e óbito. As principais co-variáveis foram idade, sexo, presença de insuficiência renal crônica, causas de hospitalização e uso de medicamentos. Proporções foram comparadas utilizando-se o teste qui-quadrado ou teste de Fischer, e, para as variáveis contínuas, o teste de Mann-Whitney foi utilizado. A mediana da idade foi 20,3 anos (15-23 e o evento clínico mais freqüente foi o episódio doloroso agudo (73,5%. O tempo m

  19. Stem cells and respiratory diseases

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    Soraia Carvalho Abreu

    2008-12-01

    Full Text Available Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases.As células-tronco têm uma infinidade de implicações clínicas no pulmão. Este artigo é uma revisão crítica que inclui estudos clínicos e experimentais advindos do banco de dados do MEDLINE e SciElo nos últimos 10 anos, onde foram destacados os efeitos da terapia celular na síndrome do desconforto respiratório agudo ou doenças mais crônicas, como fibrose pulmonar e enfisema. Apesar de muitos estudos demonstrarem os efeitos benéficos das células-tronco no desenvolvimento, reparo e remodelamento pulmonar; algumas questões ainda precisam ser respondidas para um melhor entendimento dos mecanismos que controlam a divisão celular e diferenciação, permitindo o uso da terapia celular nas doenças respiratórias.

  20. Patient-reported outcomes of deferasirox (Exjade, ICL670) versus deferoxamine in sickle cell disease patients with transfusional hemosiderosis. Substudy of a randomized open-label phase II trial.

    Science.gov (United States)

    Vichinsky, Elliott; Pakbaz, Zahra; Onyekwere, Onyinye; Porter, John; Swerdlow, Paul; Coates, Thomas; Lane, Peter; Files, Beatrice; Mueller, Brigitta U; Coïc, Lena; Forni, Gian Luca; Fischer, Roland; Marks, Peter; Rofail, Diana; Abetz, Linda; Baladi, Jean-Francois

    2008-01-01

    There is increasing evidence demonstrating the value of transfusions in sickle cell disease (SCD). However, resultant iron overload can be life threatening if untreated. Chelation therapy with deferoxamine requires parenteral infusions that can negatively impact quality of life and adherence to treatment. As part of a phase II trial, SCD patient-reported outcomes were evaluated. One hundred and ninety-five patients were randomized (2:1) to receive oral deferasirox (5-30 mg/kg/day) or deferoxamine (20-50 mg/kg, 5 days per week); 121 had previously received deferoxamine. At each time point, significantly more patients who had previously received deferoxamine were 'satisfied/very satisfied' with deferasirox, or found treatment to be 'convenient/very convenient' compared with deferoxamine (p < 0.001). In these patients, fewer hours were lost from daily activities with deferasirox than deferoxamine treatment. Most patients (77%) preferred deferasirox, and more were willing to continue taking deferasirox than deferoxamine at end-of-study (84 vs. 11%, respectively). Patients with SCD are therefore more satisfied with deferasirox, which has a lower impact on daily activities than deferoxamine. Given the high levels of satisfaction, it is likely that quality of life will be improved. These results also suggest that treatment adherence with deferasirox may be better than with deferoxamine, which should lead to improved long-term outcomes. 2008 S. Karger AG, Basel.

  1. Race and social attitudes about sickle cell disease.

    Science.gov (United States)

    Bediako, Shawn M; Moffitt, Kimberly R

    2011-01-01

    Sickle cell disease is perhaps the most racialized condition in the history of modern medicine, yet very little research has focused on how racial perceptions influence social attitudes about the disease. Subsequently, the implications of these perceptions for public health prevention efforts and the provision of clinical care are not well known. In this brief commentary, we posit that social cognitive and media framing theories provide useful approaches for assessing relations between race and social attitudes about sickle cell disease. Such inquiries might lead to more rigorous study of mechanisms that shape perceptions about sickle cell risk, interpersonal empathy toward patients, and public support for sickle cell-related policies.

  2. Gallstones in Patients with Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Xu Li

    2017-01-01

    Full Text Available With prevalence of 10–20% in adults in developed countries, gallstone disease (GSD is one of the most prevalent and costly gastrointestinal tract disorders in the world. In addition to gallstone disease, chronic liver disease (CLD is also an important global public health problem. The reported frequency of gallstone in chronic liver disease tends to be higher. The prevalence of gallstone disease might be related to age, gender, etiology, and severity of liver disease in patients with chronic liver disease. In this review, the aim was to identify the epidemiology, mechanisms, and treatment strategies of gallstone disease in chronic liver disease patients.

  3. Ethical clinical translation of stem cell interventions for neurologic disease

    DEFF Research Database (Denmark)

    Cote, David J; Bredenoord, Annelien L; Smith, Timothy R

    2017-01-01

    The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested...... in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations...... are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell...

  4. Peripheral vascular response to mild indirect cooling in patients with homozygous sickle cell (SS) disease and the frequency of painful crisis.

    Science.gov (United States)

    Mohan, J; Marshall, J M; Reid, H L; Thomas, P W; Hambleton, I; Serjeant, G R

    1998-02-01

    1. In homozygous sickle cell (SS) disease, skin cooling is a common precipitating factor of the painful crisis which is associated with avascular necrosis of active bone marrow. Since skin cooling does not directly induce sickling, we have investigated the nature of the reflex vascular responses to mild cooling in SS patients in a steady state of the disease and compared them with their history of painful crises. 2. Experiments were performed in Jamaica on 60 male SS patients and 30 matched control subjects with normal haemoglobin (AA) genotype. Forearm blood flow (FBF) was measured by venous occlusion plethysmography and mean arterial pressure (MAP) by a Finapres device: forearm vascular resistance (FVR) was calculated as MAP/FBF. Cutaneous erythrocyte flux in forearm and hand was monitored by a laser Doppler meter. The contralateral hand was immersed in cool water at 16 degrees C for 2 min, 6 times, at random intervals of 0.5-3 min. 3. The first cool immersion evoked an increase in MAP, cutaneous vasoconstriction and a net increase in FVR in both AA and SS subjects. However, the direction of change in FVR varied between individuals such that 18 AA subjects showed an increase in FVR (constrictor group) while 12 showed a decrease in FVR, indicating vasodilatation in forearm muscle (dilator group). In contrast, 50 SS subjects showed an increase in FVR and only 10 showed a decrease in FVR. The proportion of subjects who showed net vasoconstriction was significantly greater in the SS than in the AA group (83% versus 60%, P = 0.03, chi 2 test). 4. By the sixth cool stimulus, the 'dilator' group of AA subjects showed no change in FVR while the 'dilator' group of SS patients showed an increase in FVR. We suggest that forearm muscle vasodilatation was the characteristic component of the alerting/defence response to novel or noxious stimuli which habituates on repetition. 5. In the whole group of SS patients, baseline values of cutaneous vascular resistance and FVR

  5. Cranial involvement in sickle cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Alkan, Ozlem, E-mail: yalinozlem@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kizilkilic, Ebru, E-mail: ebru90@yahoo.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kizilkilic, Osman, E-mail: ebos90@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Yildirim, Tulin, E-mail: ytulin@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Karaca, Sibel, E-mail: sibelkaraca@hotmail.com [Department of Neurology, Faculty of Medicine, Baskent University, Ankara (Turkey); Yeral, Mahmut, E-mail: mahmutyeral@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kasar, Mutlu, E-mail: mutlukasar@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Ozdogu, Hakan, E-mail: hakanozdogu@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey)

    2010-11-15

    Purpose: To evaluate cranial findings in patients with neurologically symptomatic sickle cell disease (SCD). Materials and methods: We studied 50 consecutive patients with SCD and neurologic symptoms. All patients underwent brain MR examinations: all 50 underwent classic MR imaging; 42, diffusion-weighted MR imaging; 10, MR angiography; four, MR venography; and three patients, digital subtraction angiography. Results: Of the 50 SCD patients, 19 (38%) had normal MR findings, and 31 (62%) showed abnormalities on brain MR images. Of the 50 patients, 16 (32%) had ischemic lesions; two (4%), subarachnoid hemorrhage; one (2%), moya-moya pattern; one (2%), posterior reversible encephalopathy; one (2%), dural venous sinus thrombosis; 12 (24%), low marrow signal intensity and thickness of the diploic space; 12 (24%), cerebral atrophy; and two (4%), osteomyelitis. Twenty-seven patients (54%) presented with headache, which was the most common clinical finding. Conclusions: The cranial involvement is one of the most devastating complications of SCD. Early and accurate diagnosis is important in the management of cranial complications of SCD.

  6. A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Seonmi Park

    2017-04-01

    Full Text Available Summary: Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs from patients of different ethnicities, β-globin gene (HBB haplotypes, and fetal hemoglobin (HbF levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS mutation. : In this resource article, Mostoslavsky, Murphy, and colleagues of the NextGen consortium describe a diverse, comprehensive, and characterized library of sickle cell disease-specific induced pluripotent stem cells (iPSCs from patients of different ethnicities, β-globin gene (HBB haplotypes and fetal hemoglobin (HbF levels. This bank is readily available and accessible to all investigators. Keywords: induced pluripotent stem cells, iPSCs, sickle cell disease, disease modeling, directed differentiation, gene correction

  7. Immediate effects of isolated transmyocardial laser revascularization procedures combined with intramyocardial injection of autologous bone marrow stem cells in patients with terminal stage of coronary artery disease

    Directory of Open Access Journals (Sweden)

    Leo A. Bockeria

    2017-05-01

    Conclusions ― TMLR with intramyocardial autologous stem cells injections in patients with end-stage CAD is safe. This procedure can be done in the most severe group of patients who cannot be completely revascularized with either PCI or CABG surgery. Futher investigation is needed to assess the effectiveness of the procedure.

  8. T-Helper 17 Cell Cytokine Responses in Lyme Disease Correlate With Borrelia burgdorferi Antibodies During Early Infection and With Autoantibodies Late in the Illness in Patients With Antibiotic-Refractory Lyme Arthritis.

    Science.gov (United States)

    Strle, Klemen; Sulka, Katherine B; Pianta, Annalisa; Crowley, Jameson T; Arvikar, Sheila L; Anselmo, Anthony; Sadreyev, Ruslan; Steere, Allen C

    2017-04-01

    Control of Lyme disease is attributed predominantly to innate and adaptive T-helper 1 cell (TH1) immune responses, whereas the role of T-helper 17 cell (TH17) responses is less clear. Here we characterized these inflammatory responses in patients with erythema migrans (EM) or Lyme arthritis (LA) to elucidate their role early and late in the infection. Levels of 21 cytokines and chemokines, representative of innate, TH1, and TH17 immune responses, were assessed by Luminex in acute and convalescent sera from 91 EM patients, in serum and synovial fluid from 141 LA patients, and in serum from 57 healthy subjects. Antibodies to Borrelia burgdorferi or autoantigens were measured by enzyme-linked immunosorbent assay. Compared with healthy subjects, EM patients had significantly higher levels of innate, TH1, and TH17-associated mediators (P ≤ .05) in serum. In these patients, the levels of inflammatory mediators, particularly TH17-associated cytokines, correlated directly with B. burgdorferi immunoglobulin G antibodies (P ≤ .02), suggesting a beneficial role for these responses in control of early infection. Late in the disease, in patients with LA, innate and TH1-associated mediators were often >10-fold higher in synovial fluid than serum. In contrast, the levels of TH17-associated mediators were more variable, but correlated strongly with autoantibodies to endothelial cell growth factor, matrix metalloproteinase 10, and apolipoprotein B-100 in joints of patients with antibiotic-refractory LA, implying a shift in TH17 responses toward an autoimmune phenotype. Patients with Lyme disease often develop pronounced TH17 immune responses that may help control early infection. However, late in the disease, excessive TH17 responses may be disadvantageous by contributing to autoimmune responses associated with antibiotic-refractory LA. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions

  9. The obstetric management of sickle cell disease.

    Science.gov (United States)

    Howard, Jo; Oteng-Ntim, Eugene

    2012-02-01

    Sickle cell disease (SCD) is the most common inherited disease worldwide and is associated with anaemia and intermittent severe pain. Pregnant women who are affected have increased maternal and fetal mortality and morbidity. In view of this obstetricians should have an awareness of this condition and its complications, and pregnancies in women with SCD should be managed by a multidisciplinary team with experience of high risk pregnancies. Ideally women should be seen preconceptually for optimisation of their SCD and partner screening. Antenatal care should include regular outpatient visits with regular monitoring for pre-eclampsia and of fetal growth. Blood transfusion should be used for the treatment of acute anaemia, acute chest syndrome or acute stroke but there is not sufficient evidence currently to recommend its use prophylactically. There is an increased prevalence of sickle crisis during pregnancy and patients should be monitored carefully throughout this time. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Chronic complications and quality of life of patients living with sickle cell disease and receiving care in three hospitals in Cameroon: a cross-sectional study.

    Science.gov (United States)

    Andong, Anne M; Ngouadjeu, Eveline D T; Bekolo, Cavin E; Verla, Vincent S; Nebongo, Daniel; Mboue-Djieka, Yannick; Choukem, Simeon-Pierre

    2017-01-01

    Sickle Cell Disease (SCD) is associated with chronic multisystem complications that significantly influence the quality of life (QOL) of patients early in their life. Although sub-Saharan Africa bears 75% of the global burden of SCD, there is a paucity of data on these complications and their effects on the QOL. We aimed to record these chronic complications, to estimate the QOL, and to identify the corresponding risk factors in patients with SCD receiving care in three hospitals in Cameroon. In this cross-sectional study, a questionnaire was used to collect data from consecutive consenting patients. Information recorded included data on the yearly frequency of painful crisis, the types of SCD, and the occurrence of chronic complications. A 36-Item Short Form (SF-36) standard questionnaire that examines the level of physical and mental well-being, was administered to all eligible participants. Data were analyzed with STATA® software. Of 175 participants included, 93 (53.1%) were female and 111 (aged ≥14 years) were eligible for QOL assessment. The median (interquartile range, IQR) age at diagnosis was 4.0 (2.0-8.0) years and the median (IQR) number of yearly painful crisis was 3.0 (1.0-7.0). The most frequent chronic complications reported were: nocturnal enuresis, chronic leg ulcers, osteomyelitis and priapism (30.9%, 24.6%, 19.4%, and 18.3% respectively). The prevalence of stroke and avascular necrosis of the hip were 8.0% and 13.1% respectively. The median (IQR) physical and mental scores were 47.3 (43.9-58.5) and 41.0 (38.8-44.6) respectively. Age and chronic complications such as stroke and avascular necrosis were independently associated with poor QOL. In this population of patients living with SCD, chronic complications are frequent and their QOL is consequently poor. Our results highlight the need for national guidelines for SCD control, which should include new-born screening programs and strategies to prevent chronic complications.

  11. A Case Report of NK-Cell Lymphoproliferative Disease With a Wide Involvement of Digestive Tract Develop Into Epstein-Barr Virus Associated NK/T Cell Lymphoma in an Immunocompetent Patient.

    Science.gov (United States)

    Chen, Haotian; Zhang, Yu; Jiang, Zhinong; Zhou, Wei; Cao, Qian

    2016-03-01

    Epstein-Barr virus (EBV) plays an important role in various diseases. EBV-associated lymphoproliferative disease (LPD) is a rare disease with a canceration tendency. It is difficult to differentiate LPD with involvement of digestive tract from Crohn disease due to similar clinical and endoscopic manifestations. We present a case report of multiple ulcers with esophagus, small bowel and the entire colon involved, proved to be NK-Cell LPD, developed into EBV-associated NK/T Cell lymphoma, in an immunocompetent man who was initially misdiagnosed as Crohn disease.This report underscores that intestinal ulcers should be cautiously diagnosed, for it sometimes could be a precancerous lesion.

  12. Fetal microchimeric cells in autoimmune thyroid diseases

    Science.gov (United States)

    Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter

    2013-01-01

    Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD. PMID:23723083

  13. The determination of lymphocyte transformation in patients of various diseases

    International Nuclear Information System (INIS)

    Su Liaoyuan; Liu Ke Liang; Lin Xingcheng; Sun Guoqi; Xue Zhimou

    1987-01-01

    The synthesis of DNA, RNA and protein during the transformation of human lymphocytes induced by mitogen PHA and LPS was investigated by quantitation of 3 H-TdR, 14 C-UR and 14 C-valine incorporation method. 1666 tests were carried out in patients with various diseases and 424 tests in normal subjects. It was found that immunocompetence was closely related with the progress and prognosis in patients with leukemia. Impairment of the cell-mediated immunity in patients with squamous cell carcinoma and with encephlitis was observed. There was no difference in immunity between patients with adenocarcinoma and the normal subjects. The ionizing irradiation mainly exerts its effect on cell-mediated immunity. The cell-mediated immunity was found to be impaired while the humoral immune regulation was enhanced in tuberculosis and leprosy, indicating that these diseases were caused by impairment of cell-mediated immunity. Both humoral and cell-mediated immunity return to normal levels at convalescence. The uptake of 14 C-UR by lymphocytes in patients with hepatitis increased significantly. Lymphocytes reactivity was elevated in patients with vernal conjunctivities and normal in patients with uveitis. Low reactivity was observed in patients with keratitis. The immunity in various diseases was discussed

  14. A Rare Disease in Adult: Langerhans Cell Histiocytosis

    Science.gov (United States)

    Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Koroglu, Mustafa; Kaya, Emin; Unlu, Serkan

    2013-01-01

    Langerhans cell histiocytosis is a rare histiocytic disorder and has been diagnosed in all age groups, but is most common in children. This disease is very rare in adults. We presented a patient who was 62 years old man diagnosed langerhans cell histiocytosis. PMID:29147350

  15. T cells in vascular inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Lucas L Lintermans

    2014-10-01

    Full Text Available Inflammation of the human vasculature is a manifestation of many different diseases ranging from systemic autoimmune diseases to chronic inflammatory diseases, in which multiple types of immune cells are involved. For both autoimmune diseases and chronic inflammatory diseases several observations support a key role for T lymphocytes in these disease pathologies, but the underlying mechanisms are poorly understood. Previous studies in several autoimmune diseases have demonstrated a significant role for a specific subset of CD4+ T cells termed effector memory T cells. This expanded population of effector memory T cells may contribute to tissue injury and disease progression. These cells exert multiple pro-inflammatory functions through the release of effector cytokines. Many of these cytokines have been detected in the inflammatory lesions and participate in the vasculitic reaction, contributing to recruitment of macrophages, neutrophils, dendritic cells, NK cells, B cells and T cells. In addition, functional impairment of regulatory T cells paralyzes anti-inflammatory effects in vasculitic disorders. Interestingly, activation of effector memory T cells in uniquely dependent on the voltage-gated Kv1.3 potassium channel providing an anchor for specific drug targeting. In this review, we focus on the CD4+ T cells in the context of vascular inflammation and describe the evidence supporting the role of different T cell subsets in vascular inflammation. Selective targeting of pathogenic effector memory T cells might enable a more tailored therapeutic approach that avoids unwanted adverse side effects of generalized immunosuppression by modulating the effector functions of T cell responses to inhibit the development of vascular inflammation.

  16. Paediatric cardiac anaesthesia in sickle cell disease: a case series

    African Journals Online (AJOL)

    Paediatric patients with SCD and congenital heart defects may require ... Patients with sickle cell disease (SCD) presenting for cardiac ... fluid, calculated according to body weight, was initiated. ... oxygen mixture and intravenous fentanyl (5–10 mcg/kg) and .... erythropoiesis, and in this way reduces HbS production.

  17. Sport participation in adolescents with sickle cell disease.

    Science.gov (United States)

    Al-Rimawi, Hala; Jallad, Samer

    2008-10-01

    Adolescents with blood diseases should be encouraged to participate in exercise. Physical activity helps to build stronger muscles, to give better support to the joints, and to improve the patient's overall health and fitness. It also improves emotional well being by improving self-esteem and providing social interaction. Sports and exercise in sickle cell anemia and sickle cell trait need special consideration. Young athletes with sickle cell disease are at high risk of dehydration, heat-related injury, exhaustion, painful episodes, and hip joint problems. Gradual acclimatization to heat, humidity and high altitude, slow conditioning over weeks and avoidance of dehydration are recommended for all adolescents with sickle cell disease to make their sport activity safe. Effort should be made to educate those with sickle cell disease that their condition is not a handicap and that they are fit to lead a normal life.

  18. Dermatological diseases in patients with chronic kidney disease.

    Science.gov (United States)

    Gagnon1, Amy L; Desai, Tejas

    2013-04-01

    There are a variety of dermatological diseases that are more commonly seen in patients with chronic kidney disease (CKD) and renal transplants than the general population. Directory of Open Access Journals (DOAJ), Google Schol