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Sample records for advanced malignant disease

  1. Psychosocial correlates of survival in advanced malignant disease?

    PubMed

    Cassileth, B R; Lusk, E J; Miller, D S; Brown, L L; Miller, C

    1985-06-13

    Prospective studies of the general population have isolated specific social and psychological factors as independent predictors of longevity. This study assesses the ability of these factors, plus two others said to influence survival in patients with cancer, to predict survival and the time to relapse after a diagnosis of cancer. Patients with unresectable cancers (n = 204) were followed to determine the length of survival. Patients with Stage I or II melanoma or Stage II breast cancer (n = 155) were followed to determine the time to relapse. Analysis of data on these 359 patients indicates that social and psychological factors individually or in combination do not influence the length of survival or the time to relapse (P less than 0.10). The specific diagnosis (F = 2.0, P = 0.06), performance status (F = 0.66, P = 0.62), extent of disease (F = 1.12, P = 0.89), and therapy (F = 1.08, P = 0.35) were also unrelated to the psychosocial factors studied. Although these factors may contribute to the initiation of morbidity, the biology of the disease appears to predominate and to override the potential influence of life-style and psychosocial variables once the disease process is established.

  2. Rheumatic Diseases and Malignancies

    PubMed Central

    BOJINCA, Violeta; JANTA, Iustina

    2012-01-01

    ABSTRACT There are many studies which demonstrate a higher risk for malignancy in patients with rheumatic diseases. There have been a number of possible explanations for the differences in the risk of certain malignancies in patients with rheumatic disease, compared with general population, but a clear mechanism is difficult to identify. Rheumatoid syndromes may be associated with malignancy as paraneoplastic conditions, which can antedate the neoplasm diagnosis. On the other hand, autoimmune rheumatic diseases have a higher risk of malignancy by themselves or because of the immunosuppressant treatments. PMID:23482881

  3. Malignancy in Crohn's disease.

    PubMed Central

    Gyde, S N; Prior, P; Macartney, J C; Thompson, H; Waterhouse, J A; Allan, R N

    1980-01-01

    Cancer morbidity has been evaluated in a series of 513 patients with Crohn's disease under long-term review between 1944-76. In comparison with morbidity rates for cancer in the West Midlands Region (the geographical area from which these patients were drawn) the 31 tumours that occurred represented a relative risk of 1.7 (P less than 0.01) of cancer at all sites. For tumours at sites within the digestive system the relative risk was 3.3 (P less than 0.001). A significant excess of tumours was found in both the upper (P less than 0.01) and lower (P less than 0.001) gastrointestinal tract. There was no excess of tumours at any site outside the digestive system. PMID:7461462

  4. Lenvatinib and Capecitabine in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2016-09-23

    Advanced Cancer; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

  5. Surgical palliation of gastric outlet obstruction in advanced malignancy

    PubMed Central

    Potz, Brittany A; Miner, Thomas J

    2016-01-01

    Gastric outlet obstruction (GOO) is a common problem associated with advanced malignancies of the upper gastrointestinal tract. Palliative treatment of patients’ symptoms who present with GOO is an important aspect of their care. Surgical palliation of malignancy is defined as a procedure performed with the intention of relieving symptoms caused by an advanced malignancy or improving quality of life. Palliative treatment for GOO includes operative (open and laparoscopic gastrojejunostomy) and non-operative (endoscopic stenting) options. The performance status and medical condition of the patient, the extent of the cancer, the patients prognosis, the availability of a curative procedure, the natural history of symptoms of the disease (primary and secondary), the durability of the procedure, and the quality of life and life expectancy of the patient should always be considered when choosing treatment for any patient with advanced malignancy. Gastrojejunostomy appears to be associated with better long term symptom relief while stenting appears to be associated with lower immediate procedure related morbidity.

  6. Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies.

    PubMed

    Kebriaei, Partow; Huls, Helen; Jena, Bipulendu; Munsell, Mark; Jackson, Rineka; Lee, Dean A; Hackett, Perry B; Rondon, Gabriela; Shpall, Elizabeth; Champlin, Richard E; Cooper, Laurence J N

    2012-05-01

    Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo- and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR(+) T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR(+) T-cell infusions derived from allogeneic sources. PMID:22107246

  7. Infusing CD19-Directed T Cells to Augment Disease Control in Patients Undergoing Autologous Hematopoietic Stem-Cell Transplantation for Advanced B-Lymphoid Malignancies

    PubMed Central

    Kebriaei, Partow; Huls, Helen; Jena, Bipulendu; Munsell, Mark; Jackson, Rineka; Lee, Dean A.; Hackett, Perry B.; Rondon, Gabriela; Shpall, Elizabeth; Champlin, Richard E.

    2012-01-01

    Abstract Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo- and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR+ T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR+ T-cell infusions derived from allogeneic sources. PMID:22107246

  8. Life insurance after malignant disease.

    PubMed

    Fitzgerald, R H

    1981-11-01

    Forty-five life insurance companies responded to a questionnaire on insurance industry attitudes towards patients with a history of malignancy other than skin carcinoma. Although the criteria for acceptance, provisions of the policy, and philosophy about adjuvant treatment varied, all companies would underwrite such patients provided that at application there was no evidence of persistent or recurrent disease or severe complications of therapy. The concept of excess mortality (observed death rates versus standard expected death rates) is used with other factors in calculating premiums. Legal and ethical responsibilities of physicians associated with insurance applications are briefly discussed.

  9. Hodgkin's Disease and Other Malignant Lymphomas

    PubMed Central

    Rosenberg, Saul A.; Kaplan, Henry S.

    1970-01-01

    Systematic studies of the patterns of anatomic distribution, pathways of probable spread, and prognosis of the malignant lymphomas have been greatly aided by the development of new histopathologic classifications and the introduction of more sophisticated and precise diagnostic techniques, such as lymphangiography and laparotomy with splenectomy and retroperitoneal node biopsy. Concomitantly, megavoltage radiotherapy apparatus has made total-lymphoid radiotherapy feasible and practical, and the availability of a widening spectrum of chemotherapeutic agents has ushered in a new era of combination chemotherapy. Collectively, these diagnostic and therapeutic advances have already begun to yield a dramatic improvement in the prognosis of Hodgkin's disease and the other malignant lymphomas. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7. PMID:4991356

  10. Advances in management of malignant diseases with the combination of radiation therapy and chemotherapy. Highlights from the 45th Annual Meeting of the American Society for Therapeutic Radiology and Oncology.

    PubMed

    Corn, Benjamin W

    2004-01-01

    From October 19 through October 24, 2003, the American Society for Therapeutic Radiology and Oncology held its 45th Annual Meeting in Salt Lake City, Utah. The meeting was devoted to the presentation of advances in the management of malignant diseases with radiation modalities. The meeting brought together investigators, clinicians, policy makers and professionals interested in the science and impact of radiation on cancerous disease. This report examines the advances in combined modality approaches (i.e., the use of radiation therapy and chemotherapy) for the treatment of malignant disease. The American Society for Therapeutic Radiology and Oncology sponsors an annual meeting devoted to the presentation of radiation-related advances in malignant disorders. The educational elements of this program are targeted at oncologists of all disciplines (i.e., surgical oncologists, medical oncologists, radiation oncologists), physicists, biologists, nurses, and therapists as well as all health care workers who are involved in the treatment of patients with malignant diseases. The program includes presentations on standard, investigational and experimental therapeutics as well as intensity-modulated radiation therapy, treatment planning, alternative fractionation, and molecular and radiation biology. Specific clinical areas include breast, central nervous system, gastrointestinal, genitourinary, gynecological, head and neck, and lung cancers. In addition, the program addresses quality of life, supportive care and socioeconomic issues. These topics are addressed by a combination of educational sessions, panel discussions, proffered papers and posters. Since a diminishing number of tumors can be managed solely by radiation therapy, among the most noteworthy developments this year were the combined modality approaches (i.e. radiation therapy combined with chemotherapy) in the treatment of malignant disease. In particular, a cluster of seminal papers was presented pertaining to

  11. Immunotherapy advances in uro-genital malignancies.

    PubMed

    Ratta, Raffaele; Zappasodi, Roberta; Raggi, Daniele; Grassi, Paolo; Verzoni, Elena; Necchi, Andrea; Di Nicola, Massimo; Salvioni, Roberto; de Braud, Filippo; Procopio, Giuseppe

    2016-09-01

    Immunotherapy for the treatment of cancer has made significant progresses over the last 20 years. Multiple efforts have been attempted to restore immune-mediated tumor elimination, leading to the development of several targeted immunotherapies. Data from recent clinical trials suggest that these agents might improve the prognosis of patients with advanced genito-urinary (GU) malignancies. Nivolumab has been the first immune checkpoint-inhibitor approved for pre-treated patients with metastatic renal cell carcinoma. Pembrolizumab and atezolizumab have shown promising results in both phase I and II trials in urothelial carcinoma. Brentuximab vedotin has demonstrated early signals of clinical activity and immunomodulatory effects in highly pre-treated patients with testicular germ cell tumors. In this review, we have summarized the major clinical achievements of immunotherapy in GU cancers, focusing on immune checkpoint blockade as well as the new immunomodulatory monoclonal antibodies (mAbs) under clinical evaluation for these malignancies.

  12. Surgical palliation of gastric outlet obstruction in advanced malignancy.

    PubMed

    Potz, Brittany A; Miner, Thomas J

    2016-08-27

    Gastric outlet obstruction (GOO) is a common problem associated with advanced malignancies of the upper gastrointestinal tract. Palliative treatment of patients' symptoms who present with GOO is an important aspect of their care. Surgical palliation of malignancy is defined as a procedure performed with the intention of relieving symptoms caused by an advanced malignancy or improving quality of life. Palliative treatment for GOO includes operative (open and laparoscopic gastrojejunostomy) and non-operative (endoscopic stenting) options. The performance status and medical condition of the patient, the extent of the cancer, the patients prognosis, the availability of a curative procedure, the natural history of symptoms of the disease (primary and secondary), the durability of the procedure, and the quality of life and life expectancy of the patient should always be considered when choosing treatment for any patient with advanced malignancy. Gastrojejunostomy appears to be associated with better long term symptom relief while stenting appears to be associated with lower immediate procedure related morbidity. PMID:27648158

  13. Surgical palliation of gastric outlet obstruction in advanced malignancy

    PubMed Central

    Potz, Brittany A; Miner, Thomas J

    2016-01-01

    Gastric outlet obstruction (GOO) is a common problem associated with advanced malignancies of the upper gastrointestinal tract. Palliative treatment of patients’ symptoms who present with GOO is an important aspect of their care. Surgical palliation of malignancy is defined as a procedure performed with the intention of relieving symptoms caused by an advanced malignancy or improving quality of life. Palliative treatment for GOO includes operative (open and laparoscopic gastrojejunostomy) and non-operative (endoscopic stenting) options. The performance status and medical condition of the patient, the extent of the cancer, the patients prognosis, the availability of a curative procedure, the natural history of symptoms of the disease (primary and secondary), the durability of the procedure, and the quality of life and life expectancy of the patient should always be considered when choosing treatment for any patient with advanced malignancy. Gastrojejunostomy appears to be associated with better long term symptom relief while stenting appears to be associated with lower immediate procedure related morbidity. PMID:27648158

  14. Predicting Malignancy in Thyroid Nodules: Molecular Advances

    PubMed Central

    Melck, Adrienne L.; Yip, Linwah

    2016-01-01

    Over the last several years, a clearer understanding of the genetic alterations underlying thyroid carcinogenesis has developed. This knowledge can be utilized to tackle one of the greatest challenges facing thyroidologists: management of the indeterminate thyroid nodule. Despite the accuracy of fine needle aspiration cytology, many patients undergo invasive surgery in order to determine if a follicular or Hurthle cell neoplasm is malignant, and better diagnostic tools are required. A number of biomarkers have recently been studied and show promise in this setting. In particular, BRAF, RAS, PAX8-PPARγ, microRNAs and loss of heterozygosity have each been demonstrated as useful molecular tools for predicting malignancy and can thereby guide decisions regarding surgical management of nodular thyroid disease. This review summarizes the current literature surrounding each of these markers and highlights our institution’s prospective analysis of these markers and their subsequent incorporation into our management algorithms for thyroid nodules. PMID:21818817

  15. Role of stenting in gastrointestinal benign and malignant diseases

    PubMed Central

    Mangiavillano, Benedetto; Pagano, Nico; Arena, Monica; Miraglia, Stefania; Consolo, Pierluigi; Iabichino, Giuseppe; Virgilio, Clara; Luigiano, Carmelo

    2015-01-01

    Advances in stents design have led to a substantial increase in the use of stents for a variety of digestive diseases. Initially developed as a non-surgical treatment for palliation of esophageal cancer, the stents now have an emerging role in the management of malignant and benign conditions as well as in all segments of the gastrointestinal tract. In this review, relevant literature search and expert opinions have been used to evaluate the key-role of stenting in gastrointestinal benign and malignant diseases. PMID:25992186

  16. Photodynamic therapy of advanced malignant tumors

    NASA Astrophysics Data System (ADS)

    Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

    1993-03-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

  17. Radiation of pelvic malignant disease.

    PubMed

    BARNES, A C

    1957-02-01

    At present, progress in the treatment of cancer consists of more extensive excision or more thorough irradiation. The cure rate of pelvic cancer is proportionate not so much with the form of therapy used as with the stage of the disease when first diagnosed. Any woman who consults a physician should have a pelvic examination regardless of the presence or absence of pelvic symptoms.

  18. Musculoskeletal manifestations in patients with malignant disease.

    PubMed

    Gheita, Tamer A; Ezzat, Yasser; Sayed, Safaa; El-Mardenly, Ghada; Hammam, Waleed

    2010-02-01

    To detect and describe the incidence of musculoskeletal manifestations in different malignant diseases as well as their relation to the treatment received whether by chemotherapy or radiation therapy. Sixty patients with different malignant diseases were included in this study, 45 with solid tumors and 15 patients with hematological malignancy. The mean age was 46.55 +/- 11.04 years and the mean disease duration was 2 +/- 0.75 years. The patients were fully examined for any rheumatologic involvement, laboratory investigations were performed as well as dual energy X-ray absorptiometry study for bone densitometry. Treatment strategies were assessed including the chemotherapeutics, radiation therapy, and/or surgery. Myalgias and arthralgias were the most frequent followed by flexor tenosynovitis, frozen shoulder, and fibromyalgia syndrome. Hypertrophic osteoarthropathy was seen in five patients, cutaneous vasculitis in two patients as well as arthritis. Osteonecrosis was present in one of the lunate carpal bones of a patient with non-Hodgkin's lymphoma (1.67%) and receiving high dose steroids. Rheumatoid factor was positive in four patients, three of which had hepatitis C virus positivity and cryoglobulins. Anti-neutrophil cytoplasmic antibody was negative in all the studied patients. The bone mineral density was significantly reduced in the patients with malignancy compared to the control. Mild to moderate osteoporosis was present, being more evident in the spine and forearm. The bone loss was higher in those with solid tumors and even more obvious in those receiving aromatase inhibitors. Musculoskeletal manifestations occurring during malignancies and following the treatment represent a significant percentage of symptoms and signs which may raise a clue to differential diagnosis.

  19. Adult Celiac Disease and Its Malignant Complications

    PubMed Central

    2009-01-01

    Adult celiac disease is a chronic intestinal disorder that has been estimated to affect up to 1-2% of the population in some nations. Awareness of the disease has increased, but still it remains markedly underdiagnosed. Celiac disease is a pathologically defined condition with several characteristic clinical scenarios that should lead the clinician to suspect its presence. Critical to diagnosis is a documented responsiveness to a gluten-free diet. After diagnosis and treatment, symptoms and biopsy-proven changes may recur and appear refractory to a gluten-free diet. Recurrent symptoms are most often due to poor diet compliance, a ubiquitous and unrecognized gluten source, an initially incorrect diagnosis, or an associated disease or complication of celiac disease. Some patients with persistent symptoms and biopsy-proven changes may not have celiac disease at all, instead suffering from a sprue-like intestinal disease, so-called unclassified sprue, which is a specific entity that does not appear to respond to a gluten-free diet. Some of these patients eventually prove to have an underlying malignant cause, particularly lymphoma. The risk of developing lymphoma and other malignancies is increased in celiac disease, especially if initially diagnosed in the elderly, or late in the clinical course of the disease. However, recent studies suggest that the risk of gastric and colon cancer is low. This has led to the hypothesis that untreated celiac disease may be protective, possibly due to impaired absorption and more rapid excretion of fat or fat-soluble agents, including hydrocarbons and other putative cocarcinogens, which are implicated in the pathogenesis of colorectal cancer. PMID:20431755

  20. [Palliation of dyspnea in malignant disease].

    PubMed

    de la Fuente Fonnest, I; Hjortshøj, K M; Strömgren, L A

    1999-01-18

    Dyspnea is a symptom experienced by more than half of all cancer patients in their terminal illness, and it is thus a severe problem for patients, relatives, and professionals. Dyspnea in a cancer patient may have a non-malignant origin that may be treated causally. If dyspnea is caused directly by the malignant disease, antineoplastic treatment needs to be considered. In case this is not feasible, one must seek to modify the manifestations of illness. When this is not possible, one must relieve the patient's experience of dyspnea. To this end there are a number of possibilities, pharmacological as well as non-pharmacological. Opioids given systemically cause respiratory depression. Unfortunately, this has given rise to an overly cautious attitude when facing the terminal patient with dyspnea. However, other treatment modalities are often exhausted and opioids, if indicated in combination with anxiolytics, do have a palliative effect on dyspnea.

  1. Advances in Optical Adjunctive Aids for Visualisation and Detection of Oral Malignant and Potentially Malignant Lesions

    PubMed Central

    Bhatia, Nirav; Lalla, Yastira; Vu, An N.; Farah, Camile S.

    2013-01-01

    Traditional methods of screening for oral potentially malignant disorders and oral malignancies involve a conventional oral examination with digital palpation. Evidence indicates that conventional examination is a poor discriminator of oral mucosal lesions. A number of optical aids have been developed to assist the clinician to detect oral mucosal abnormalities and to differentiate benign lesions from sinister pathology. This paper discusses advances in optical technologies designed for the detection of oral mucosal abnormalities. The literature regarding such devices, VELscope and Identafi, is critically analysed, and the novel use of Narrow Band Imaging within the oral cavity is also discussed. Optical aids are effective in assisting with the detection of oral mucosal abnormalities; however, further research is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant and malignant lesions. PMID:24078812

  2. [Treatment strategy for patients with simultaneous cardiac and malignant diseases].

    PubMed

    Osawa, Hisayoshi; Muraki, Satoshi; Sakurada, Taku; Kawaharada, Nobuyoshi; Sasaki, Jun; Araki, Eiji; Nakashima, Shinji

    2014-03-01

    The choice of treatment strategy for patients with simultaneous cardiac and malignant diseases is often debatable. We report 11 patients with simultaneous cardiac and malignant diseases who were hospitalized in our institution over the past 6 years. The patients were 9 males and 2 females with a mean age of 71.9±9.0 years old. There were 7 cases of ischemic heart disease( IHD), and 4 cases of valvular disease. Malignant diseases consisted of 4 cases of colon cancer, 2 cases of pulmonary cancer, 2 cases of hepatic cancer, and 1 case each of sigmoid colon cancer with liver metastasis, gallbladder cancer, and pancreatic cancer. Eight of the 11 cases(73%)were hospitalized because of a symptom associated with cardiac disease, and malignant disease was diagnosed incidentally during examination or treatment. Four of the IHD cases preceded coronary revascularization by off-pump coronary artery bypass grafting (OPCAB) or percutaneous coronary intervention (PCI). Two of the valvular cases and 2 of the IHD cases underwent cardiac surgery after treatment of malignant diseases. In 3 cases, only 1 of the diseases was treated. Seven cases died of malignant diseases at the present. The choice of treatment strategy should be established for patients with simultaneous cardiac and malignant diseases in consideration of the severity of the cardiac disease and the expected prognosis of the malignant disease because there is no standardized method of treatment.

  3. Arsenic and non-malignant lung disease.

    PubMed

    Guha Mazumder, D N

    2007-10-01

    Many aquifers in various parts of the world have been found to be contaminated with arsenic at concentration above 0.05 mg/L. However reports of large number of affected people in India and Bangladesh are unprecedented. Characteristic skin lesions (pigmentation, depigmentation and keratosis) are the hallmark signs of chronic arsenic toxicity. Emerging evidences show that ingestion of arsenic through drinking water may also lead to non-malignant respiratory effects. Early report of non-malignant pulmonary effect of chronic ingestion of arsenic was available from studies in children in Chile as early as 1970. However on the basis of case studies, respiratory effect of chronic arsenic toxicity in adults following drinking of arsenic contaminated water in West Bengal was first reported in 1997. Epidemiological studies carried out in West Bengal on a population of 7683 showed that the prevalence odds ratio (POR) estimates were markedly increased for participants with arsenic induced skin lesions who also had high levels of arsenic in their current drinking water source (> or = 0.5 mg/L) compared with individuals who had normal skin and were exposed to low levels of arsenic (< 0.05 mg/L). In participants with skin lesions, age-adjusted POR estimates for chronic cough were 7.8 for females (95% CI:3.1-19.5) and 5.0 for males (95% CI:2.6-9.9). In Bangladesh, similar study carried out on a population of 218 showed that the crude prevalence ratio for chronic bronchitis was found to be 10.3 (95% CI:2.4-43.1) for females and 1.6 (95% CI:0.8-3.1) for males. Reports of lung function tests were available from both hospital and population based studies. Results show evidences of restrictive, obstructive and combined obstructive and restrictive lung disease in different people having chronic lung disease associated with chronic arsenic toxicity. On the basis of clinical study, chest X-ray and HRCT done in Arsenicosis patients with features of chronic lung disease, the abnormalities

  4. Molecular and Therapeutic Advances in the Diagnosis and Management of Malignant Pheochromocytomas and Paragangliomas

    PubMed Central

    Lowery, Aoife J.; Walsh, Siun; McDermott, Enda W.

    2013-01-01

    Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors derived from chromaffin cells originating in the neural crest. These tumors represent a significant diagnostic and therapeutic challenge because the diagnosis of malignancy is frequently made in retrospect by the development of metastatic or recurrent disease. Complete surgical resection offers the only potential for cure; however, recurrence can occur even after apparently successful resection of the primary tumor. The prognosis for malignant disease is poor because traditional treatment modalities have been limited. The last decade has witnessed exciting discoveries in the study of PCCs and PGLs; advances in molecular genetics have uncovered hereditary and germline mutations of at least 10 genes that contribute to the development of these tumors, and increasing knowledge of genotype-phenotype interactions has facilitated more accurate determination of malignant potential. Elucidating the molecular mechanisms responsible for malignant transformation in these tumors has opened avenues of investigation into targeted therapeutics that show promising results. There have also been significant advances in functional and radiological imaging and in the surgical approach to adrenalectomy, which remains the mainstay of treatment for PCC. In this review, we discuss the currently available diagnostic and therapeutic options for patients with malignant PCCs and PGLs and detail the molecular rationale and clinical evidence for novel and emerging diagnostic and therapeutic strategies. PMID:23576482

  5. Oncolytic virotherapy for human malignant mesothelioma: recent advances

    PubMed Central

    Boisgerault, Nicolas; Achard, Carole; Delaunay, Tiphaine; Cellerin, Laurent; Tangy, Frédéric; Grégoire, Marc; Fonteneau, Jean-François

    2015-01-01

    Cancer virotherapy is an attractive alternative to conventional treatments because it offers a wide range of antitumor effects due to 1) the diversity of the oncolytic viruses that are now available and 2) their multifaceted activities against both tumor cells and tumor vessels, in addition to their ability to induce antitumor immune responses. In this review, we summarize preclinical and clinical data regarding the targeting of malignant mesothelioma (MM) by oncolytic viruses. We also discuss the potential of other oncolytic viruses that have already shown antitumor effects against several malignancies in advanced clinical trials but are yet to be tested against MM cells. Finally, we review how the activation of the immune system and combinations with other types of anticancer treatments could support the development of oncolytic virotherapy for the treatment of MM. PMID:27512676

  6. Palliative care for patients with non-malignant respiratory disease.

    PubMed

    McVeigh, Clare

    2015-05-01

    Non-malignant respiratory disease is a chronic life-limiting condition that requires holistic palliative care. Patients with non-malignant respiratory disease have a range of biopsychosocial and spiritual needs, which healthcare professionals should recognise and manage effectively. Healthcare professionals have an important role in enabling the delivery of effective palliative care to this group of patients and their carers, and in recognising the many factors that may impede delivery of palliative care. PMID:25942985

  7. Management of metastatic malignant thymoma with advanced radiation and chemotherapy techniques: report of a rare case.

    PubMed

    D'Andrea, Mark A; Reddy, G Kesava

    2015-02-25

    Malignant thymomas are rare epithelial neoplasms of the anterior superior mediastinum that are typically invasive in nature and have a higher risk of relapse that may ultimately lead to death. Here we report a case of an advanced malignant thymoma that was successfully treated with neoadjuvant chemotherapy followed by surgical resection and subsequently with advanced and novel radiation therapy techniques. A 65-year-old male was diagnosed with a stage IV malignant thymoma with multiple metastatic lesions involving the left peripheral lung and pericardium. Initial neoadjuvant chemotherapy with a cisplatin-based regimen resulted in a partial response allowing the inoperable tumor to become operable. Following surgical resection of the residual disease, the tumor recurred within a year. The patient then underwent a course of targeted three-dimensional intensity modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT). Five years after radiation therapy, the localized soft tissue thickening at the left upper lung anterior pleural space had resolved. Seven years after radiation therapy the tumor mass had completely resolved. No recurrences were seen and the patient is well even 8 years after IMRT/IGRT with a favorable outcome. Chemotherapy with targeted three-dimensional IMRT/IGRT should be considered the primary modality for the management of advanced malignant thymoma patients.

  8. Cause-Specific Mortality Due to Malignant and Non-Malignant Disease in Korean Foundry Workers

    PubMed Central

    Yoon, Jin-Ha; Ahn, Yeon-Soon

    2014-01-01

    Background Foundry work is associated with serious occupational hazards. Although several studies have investigated the health risks associated with foundry work, the results of these studies have been inconsistent with the exception of an increased lung cancer risk. The current study evaluated the mortality of Korean foundry workers due to malignant and non-malignant diseases. Methods This study is part of an ongoing investigation of Korean foundry workers. To date, we have observed more than 150,000 person-years in male foundry production workers. In the current study, we stratified mortality ratios by the following job categories: melting-pouring, molding-coremaking, fettling, and uncategorized production work. We calculated standard mortality ratios (SMR) of foundry workers compare to general Korean men and relative risk (RR) of mortality of foundry production workers reference to non-production worker, respectively. Results Korean foundry production workers had a significantly higher risk of mortality due to malignant disease, including stomach (RR: 3.96; 95% CI: 1.41–11.06) and lung cancer (RR: 2.08; 95% CI: 1.01–4.30), compared with non-production workers. High mortality ratios were also observed for non-malignant diseases, including diseases of the circulatory (RR: 1.92; 95% CI: 1.18–3.14), respiratory (RR: 1.71; 95% CI: 1.52–21.42 for uncategorized production worker), and digestive (RR: 2.27; 95% CI: 1.22–4.24) systems, as well as for injuries (RR: 2.36; 95% CI: 1.52–3.66) including suicide (RR: 3.64; 95% CI: 1.32–10.01). Conclusion This study suggests that foundry production work significantly increases the risk of mortality due to some kinds of malignant and non-malignant diseases compared with non-production work. PMID:24505454

  9. Advanced Coats' disease.

    PubMed Central

    Haik, B G

    1991-01-01

    Advanced Coats' disease and retinoblastoma can both present with the triad of a retinal detachment, the appearance of a subretinal mass, and dilated retinal vessels. Thus, even the most experienced observer may not be able to differentiate these entities on ophthalmoscopic findings alone. Coats' disease is the most common reason for which eyes are enucleated with the misdiagnosis of retinoblastoma. Ultrasonography is the auxiliary diagnostic test most easily incorporated into the clinical examination, and can be utilized repeatedly without biologic tissue hazard. Ultrasonically identifiable features allowing differentiation between Coats' disease and retinoblastoma include the topography and character of retinal detachment and presence or absence of subretinal calcifications. Ultrasonography is of lesser use in poorly calcified retinoblastoma and in detecting optic nerve or extraocular extension in heavily calcified retinoblastoma. CT is perhaps the single most valuable test because of its ability to: (a) delineate intraocular morphology, (b) quantify subretinal densities, (c) identify vascularities within the subretinal space through the use of contrast enhancement, and (d) detected associated orbital or intracranial abnormalities. Optimal computed tomographic studies, however, require multiple thin slices both before and after contrast introduction and expose the child to low levels of radiation if studies are repeated periodically. MR imaging is valuable for its multiplanar imaging capabilities, its superior contrast resolution, and its ability to provide insights into the biochemical structure and composition of tissues. It is limited in its ability to detect calcium, which is the mainstay of ultrasonic and CT differentiation. Aqueous LDH and isoenzyme levels were not valuable in distinguishing between Coats' disease and retinoblastoma. The value of aqueous NSE levels in the differentiation of advanced Coats' disease and exophytic retinoblastoma deserves

  10. Vaccines and Immunotherapeutics for the Treatment of Malignant Disease

    PubMed Central

    Aldrich, Joel F.; Lowe, Devin B.; Shearer, Michael H.; Winn, Richard E.; Jumper, Cynthia A.; Kennedy, Ronald C.

    2010-01-01

    The employment of the immune system to treat malignant disease represents an active area of biomedical research. The specificity of the immune response and potential for establishing long-term tumor immunity compels researchers to continue investigations into immunotherapeutic approaches for cancer. A number of immunotherapeutic strategies have arisen for the treatment of malignant disease, including various vaccination schemes, cytokine therapy, adoptive cellular therapy, and monoclonal antibody therapy. This paper describes each of these strategies and discusses some of the associated successes and limitations. Emphasis is placed on the integration of techniques to promote optimal scenarios for eliminating cancer. PMID:20936120

  11. BMT Abatacept for Non-Malignant Diseases

    ClinicalTrials.gov

    2016-08-16

    Hurler Syndrome; Fanconi Anemia; Glanzmann Thrombasthenia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; Severe Congenital Neutropenia; Leukocyte Adhesion Deficiency; Shwachman-Diamond Syndrome; Diamond-Blackfan Anemia; Dyskeratosis-congenita; Chediak-Higashi Syndrome; Severe Aplastic Anemia; Thalassemia Major; Hemophagocytic Lymphohistiocytosis; Sickle Cell Disease

  12. Cholangiocarcinoma and malignant bile duct obstruction: A review of last decades advances in therapeutic endoscopy

    PubMed Central

    Bertani, Helga; Frazzoni, Marzio; Mangiafico, Santi; Caruso, Angelo; Manno, Mauro; Mirante, Vincenzo Giorgio; Pigò, Flavia; Barbera, Carmelo; Manta, Raffaele; Conigliaro, Rita

    2015-01-01

    In the last decades many advances have been achieved in endoscopy, in the diagnosis and therapy of cholangiocarcinoma, however blood test, magnetic resonance imaging, computed tomography scan may fail to detect neoplastic disease at early stage, thus the diagnosis of cholangiocarcinoma is achieved usually at unresectable stage. In the last decades the role of endoscopy has moved from a diagnostic role to an invaluable therapeutic tool for patients affected by malignant bile duct obstruction. One of the major issues for cholangiocarcinoma is bile ducts occlusion, leading to jaundice, cholangitis and hepatic failure. Currently, endoscopy has a key role in the work up of cholangiocarcinoma, both in patients amenable to surgical intervention as well as in those unfit for surgery or not amenable to immediate surgical curative resection owing to locally advanced or advanced disease, with palliative intention. Endoscopy allows successful biliary drainage and stenting in more than 90% of patients with malignant bile duct obstruction, and allows rapid reduction of jaundice decreasing the risk of biliary sepsis. When biliary drainage and stenting cannot be achieved with endoscopy alone, endoscopic ultrasound-guided biliary drainage represents an effective alternative method affording successful biliary drainage in more than 80% of cases. The purpose of this review is to focus on the currently available endoscopic management options in patients with cholangiocarcinoma. PMID:26078827

  13. Endobronchial valve placement as destination therapy for recurrent pneumothorax in the setting of advanced malignancy.

    PubMed

    Gilbert, Christopher R; Toth, Jennifer W; Osman, Umar; Reed, Michael F

    2015-03-01

    The development of a persistent air leak after pneumothorax can be encountered in patients with underlying structural lung disease. In those with advanced malignancy or other comorbidities, the ability to tolerate general anesthesia and thoracoscopic procedures may limit definitive management. We describe the case of a 68-y-old male with refractory acute myelogenous leukemia presenting with recurrent secondary spontaneous pneumothorax and persistent air leak related to an underlying fungal pneumonia. Endobronchial valve placement allowed for timely chest tube removal and discharge from the hospital, as well as avoidance of a thoracoscopic procedure and pleurodesis.

  14. Second malignant lesions after therapy for Hodgkin's disease

    SciTech Connect

    Schomberg, P.J.; Evans, R.G.; Banks, P.M.; White, W.L.; O'Connell, M.J.; Earle, J.D.

    1984-07-01

    Among 169 adult pathologically staged patients with Hodgkin's disease who were treated at the Mayo Clinic between 1974 and 1978, four cases of second malignant lesions were identified. The median duration of follow-up after diagnosis for the entire population was 4.1 years. Of the 169 patients, 73 received irradiation only, 19 received chemotherapy only, and 77 received both chemotherapy and radiation therapy. In all four patients with second malignant lesions, Hodgkin's disease was in apparent remission at the time of diagnosis of the second tumor. These four patients had received either total nodal irradiation or six or more cycles of chemotherapy as initial treatment (and one of them had received both treatment modalities). Thus, intensive therapy might be hypothesized to have played a role in the development of the second malignant tumor. The development of non-Hodgkin's lymphoma within a previously irradiated field after treatment of Hodgkin's disease with radiation therapy only is not know to have been reported previously. Although further studies with longer follow-up should be conducted, this analysis supports a definite risk for development of a second malignant lesion not only after combined-modality treatment or chemotherapy for Hodgkin's disease but also after irradiation only.

  15. Percutaneous antegrade ureteric stent insertion in malignant disease.

    PubMed Central

    Harding, J R

    1993-01-01

    Untreated, progressive bilateral ureteric obstruction, or unilateral ureteric obstruction in patients with a solitary functioning kidney, will ultimately lead to uraemia, renal failure and death. This paper describes 34 successful percutaneous antegrade ureteric stent placements from 37 attempts, performed on 25 selected patients with a history of malignant disease, in whom retrograde ureteric stenting was impossible or difficult. PMID:8410885

  16. Glomerular diseases and cancer: evaluation of underlying malignancy.

    PubMed

    Pani, Antonello; Porta, Camillo; Cosmai, Laura; Melis, Patrizia; Floris, Matteo; Piras, Doloretta; Gallieni, Maurizio; Rosner, Mitchell; Ponticelli, Claudio

    2016-04-01

    Onconephrology is an emerging medical subspecialty focused on the numerous interconnections between cancer and kidney diseases. Patient with malignancies commonly experience kidney problems including acute kidney injury, tumor lysis syndrome, fluid and electrolyte disorders and chronic kidney disease, often as a consequence of the anti-cancer treatment. Conversely, a number of glomerulopathies, tubulopathies and vascular renal diseases can early signal the presence of an underlying cancer. Furthermore, the administration of immunosuppressive drugs, especially cytotoxic drugs and calcineurin inhibitors, may strongly impair the immune response increasing the risk of cancer. The objective of this review article is to: (i) discuss paraneoplastic glomerular disease, (ii) review cancer as an adverse effect of immunosuppressive agents used to treat glomerulopathies, and (iii) in the absence of international approved guidelines, propose a screening program based on expert opinion aimed at guiding nephrologists to early detect malignancies during their clinical practice. PMID:26498294

  17. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

    PubMed

    Kahl, Christoph; Storer, Barry E; Sandmaier, Brenda M; Mielcarek, Marco; Maris, Michael B; Blume, Karl G; Niederwieser, Dietger; Chauncey, Thomas R; Forman, Stephen J; Agura, Edward; Leis, Jose F; Bruno, Benedetto; Langston, Amelia; Pulsipher, Michael A; McSweeney, Peter A; Wade, James C; Epner, Elliot; Bo Petersen, Finn; Bethge, Wolfgang A; Maloney, David G; Storb, Rainer

    2007-10-01

    Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m(2); n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT.

  18. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning

    PubMed Central

    Kahl, Christoph; Storer, Barry E.; Sandmaier, Brenda M.; Mielcarek, Marco; Maris, Michael B.; Blume, Karl G.; Niederwieser, Dietger; Chauncey, Thomas R.; Forman, Stephen J.; Agura, Edward; Leis, Jose F.; Bruno, Benedetto; Langston, Amelia; Pulsipher, Michael A.; McSweeney, Peter A.; Wade, James C.; Epner, Elliot; Bo Petersen, Finn; Bethge, Wolfgang A.; Maloney, David G.

    2007-01-01

    Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m2; n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT. PMID:17595333

  19. Advances in local ablation of malignant liver lesions.

    PubMed

    Eisele, Robert M

    2016-04-21

    Local ablation of liver tumors matured during the recent years and is now proven to be an effective tool in the treatment of malignant liver lesions. Advances focus on the improvement of local tumor control by technical innovations, individual selection of imaging modalities, more accurate needle placement and the free choice of access to the liver. Considering data found in the current literature for conventional local ablative treatment strategies, virtually no single technology is able to demonstrate an unequivocal superiority. Hints at better performance of microwave compared to radiofrequency ablation regarding local tumor control, duration of the procedure and potentially achievable larger size of ablation areas favour the comparably more recent treatment modality; image fusion enables more patients to undergo ultrasound guided local ablation; magnetic resonance guidance may improve primary success rates in selected patients; navigation and robotics accelerate the needle placement and reduces deviation of needle positions; laparoscopic thermoablation results in larger ablation areas and therefore hypothetically better local tumor control under acceptable complication rates, but seems to be limited to patients with no, mild or moderate adhesions following earlier surgical procedures. Apart from that, most techniques appear technically feasible, albeit demanding. Which technology will in the long run become accepted, is subject to future work. PMID:27099433

  20. Advances in local ablation of malignant liver lesions

    PubMed Central

    Eisele, Robert M

    2016-01-01

    Local ablation of liver tumors matured during the recent years and is now proven to be an effective tool in the treatment of malignant liver lesions. Advances focus on the improvement of local tumor control by technical innovations, individual selection of imaging modalities, more accurate needle placement and the free choice of access to the liver. Considering data found in the current literature for conventional local ablative treatment strategies, virtually no single technology is able to demonstrate an unequivocal superiority. Hints at better performance of microwave compared to radiofrequency ablation regarding local tumor control, duration of the procedure and potentially achievable larger size of ablation areas favour the comparably more recent treatment modality; image fusion enables more patients to undergo ultrasound guided local ablation; magnetic resonance guidance may improve primary success rates in selected patients; navigation and robotics accelerate the needle placement and reduces deviation of needle positions; laparoscopic thermoablation results in larger ablation areas and therefore hypothetically better local tumor control under acceptable complication rates, but seems to be limited to patients with no, mild or moderate adhesions following earlier surgical procedures. Apart from that, most techniques appear technically feasible, albeit demanding. Which technology will in the long run become accepted, is subject to future work. PMID:27099433

  1. Simultaneous operation for cardiac disease and gastrointestinal malignancy

    PubMed Central

    Komokata, Teruo; Fukueda, Mikio; Kaieda, Mamoru; Ueno, Takayuki; Iguro, Yoshihumi; Imoto, Yutaka; Sakata, Ryuzo

    2014-01-01

    AIM: To investigate the safety of performing simultaneous cardiac surgery and a resection of a gastrointestinal malignancy. METHODS: Among 3664 elective cardiac operations performed in adults at Kagoshima University Hospital from January 1991 to October 2009, this study reviewed the clinical records of the patients who underwent concomitant cardiac surgery and a gastrointestinal resection. Such simultaneous surgeries were performed in 15 patients between January 1991 and October 2009. The cardiac diseases included 8 cases of coronary artery disease and 7 cases with valvular heart disease. Gastrointestinal malignancies included 11 gastric and 4 colon cancers. Immediate postoperative and long-term outcomes were evaluated. RESULTS: Postoperative complications occurred in 5 patients (33.3%), including strokes (n = 1), respiratory failure requiring re-intubation (n = 1), hemorrhage (n = 2), hyperbilirubinemia (n = 1) and aspiration pneumonia (n = 1). There was 1 hospital death caused by the development of adult respiratory distress syndrome after postoperative surgical bleeding followed aortic valve replacement plus gastrectomy. There was no cardiovascular event in the patients during the follow-up period. The cumulative survival rate for all patients was 69.2% at 5 years. CONCLUSION: Simultaneous procedures are acceptable for the patients who require surgery for both cardiac diseases and gastrointestinal malignancy. In particular, the combination of a standard cardiac operation, such as coronary artery bypass grafting or an isolated valve replacement and simple gastrointestinal resection, such as gastrectomy or colectomy can therefore be safely performed. PMID:25161762

  2. Advances in tropical diseases.

    PubMed

    Ramos-E-Silva, M; Silveira Lima, T

    2011-10-01

    There are six diseases that WHO considers as the major threat in developing countries, leprosy, filariasis, malaria, schistosomiasis, Chagas disease and leishmaniasis; and of these only malaria does not present skin lesions. These diseases are among the so called tropical diseases found in countries of tropical climate, usually infections and infestations considered exotic and rare in European and North American countries. It is extremely important for doctors of all countries to be able to provide correct pre travel counseling and to make early diagnosis and treatment, thus avoiding dissemination of these dieases to non endemic areas. The authors review some important tropical diseases seen in Brazil, as paracoccidiodomycosis, lobomycosis, myiasis, tungiasis, and cutaneous schistosomiasis and discuss new information about them. PMID:21956272

  3. Bacterial Infections Following Splenectomy for Malignant and Nonmalignant Hematologic Diseases

    PubMed Central

    Leone, Giuseppe; Pizzigallo, Eligio

    2015-01-01

    Splenectomy, while often necessary in otherwise healthy patients after major trauma, finds its primary indication for patients with underlying malignant or nonmalignant hematologic diseases. Indications of splenectomy for hematologic diseases have been reducing in the last few years, due to improved diagnostic and therapeutic tools. In high-income countries, there is a clear decrease over calendar time in the incidence of all indication splenectomy except nonmalignant hematologic diseases. However, splenectomy, even if with different modalities including laparoscopic splenectomy and partial splenectomy, continue to be a current surgical practice both in nonmalignant hematologic diseases, such as Immune Thrombocytopenic Purpura (ITP), Autoimmune Hemolytic Anemia (AIHA), Congenital Hemolytic Anemia such as Spherocytosis, Sickle Cell Anemia and Thalassemia and Malignant Hematological Disease, such as lymphoma. Today millions of people in the world are splenectomized. Splenectomy, independently of its cause, induces an early and late increase in the incidence of venous thromboembolism and infections. Infections remain the most dangerous complication of splenectomy. After splenectomy, the levels of antibody are preserved but there is a loss of memory B cells against pneumococcus and tetanus, and the loss of marginal zone monocytes deputed to immunological defense from capsulated bacteria. Commonly, the infections strictly correlated to the absence of the spleen or a decreased or absent splenic function are due to encapsulated bacteria that are the most virulent pathogens in this set of patients. Vaccination with polysaccharide and conjugate vaccines again Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis should be performed before the splenectomy. This practice reduces but does not eliminate the occurrence of overwhelming infections due to capsulated bacteria. At present, most of infections found in splenectomized patients are due to Gram

  4. Surgery of advanced malignant epithelial tumours of the ovary.

    PubMed

    Favalli, G; Odicino, F; Pecorelli, S

    2000-01-01

    Surgery is still the cornerstone in the management of advanced epithelial ovarian cancer (AEOC) patients. It involves: i. establishment of diagnosis and staging; ii. primary cytoreduction; iii. interval cytoreduction, interval debulking surgery (IDS) or surgery after neoadjuvant chemotherapy; iv. secondary cytoreduction during the assessment of the status of the disease at the end of primary chemotherapy - second look; v. surgery for recurrence; vi. palliation. Substantial evidence exists to demonstrate that if surgery is performed by gynaecologists with a special training in gynaecological oncology, a survival advantage can be achieved when compared with that obtained when general surgeons are primarily treating AEOC. Primary surgery with diagnostic and cytoreductive intent should be performed in accordance with the European Guidelines of Staging in Ovarian Cancer. Whether or not cytoreduction should systematically include lymphadenectomy is still a controversial issue. The strong correlation between chemosensitivity, successful debulking surgery and survival strongly support the concept that it is the biological characteristic of the disease rather than the aggressiveness of the surgeon to allow a successful cytoreduction to the real optimal disease status. It should be now recognised as the complete absence of disease at the end of the surgical procedure. Both IDS and neoadjuvant chemotherapy represent a strong effort to achieve such a status through less morbidity and a better quality of life for the patient. Surgery for recurrence and palliation need to be optimised both in terms of patient selection and a better integration with chemotherapy and ancillary management.

  5. Malignant disease in childhood: the problems in general practice.

    PubMed

    Jones, P G

    1977-03-01

    The role of the family doctor with regard to malignant disease in childhood, can be summarized as follows: To act appropriately so that early diagnosis, which to an important degree determines the prognosis, is not delayed by a justifiably low index of suspicion. To assist the family, including the siblings, to cope with the severe emotional stress inherpent in the diagnosis of a malignancy in a child. To recognize the extreme danger of chicken pox and measles when contracted during chemotherapy, for cytotoxic drugs are also immune-suppressants, and appropriate immune globulins can be life-saving. To arrange for and cooperate in the support necessary when a child is nursed at home in the terminal stages.

  6. Massive chest wall resection and reconstruction for malignant disease

    PubMed Central

    Foroulis, Christophoros N; Kleontas, Athanassios D; Tagarakis, George; Nana, Chryssoula; Alexiou, Ioannis; Grosomanidis, Vasilis; Tossios, Paschalis; Papadaki, Elena; Kioumis, Ioannis; Baka, Sofia; Zarogoulidis, Paul; Anastasiadis, Kyriakos

    2016-01-01

    during the study period because of recurrent disease or complications of treatment for recurrent disease. Conclusion Chest wall tumors are in their majority mesenchymal neoplasms, which often require major chest wall resection for their eradication. Long-term survival is expected in low-grade tumors where a radical resection is achieved, while big tumors and histology of malignant fibrous histiocytoma are connected with the increase rate of recurrence. PMID:27143930

  7. Advances in haploidentical stem cell transplantation for hematologic malignancies.

    PubMed

    Montoro, Juan; Sanz, Jaime; Sanz, Guillermo F; Sanz, Miguel A

    2016-08-01

    One of the most important advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the use of alternative donors and cell sources, such as haploidentical transplants (haplo-HSCT) from family donors. Several approaches have been developed to overcome the challenging bidirectional alloreactivity. We discuss these approaches, including ex vivo T-cell-depleted grafts with megadose of CD34(+) cells, not requiring immunosuppression after allogeneic transplantation for graft-versus-host disease (GVHD) prophylaxis, and other strategies using unmanipulated T-cell-replete grafts with intensive immunosuppression or post-transplantation cyclophosphamide to minimize the GVHD. We also address the role of other strategies developed in the context of the haplo-HSCT platforms, such as ex vivo selective depletion of alloreactive donor T-cell subpopulations, infusion of antigen-specific T-cells against several pathogens, and infusion of regulatory T-cells, among other experimental approaches. Finally, some considerations about the selection of the most suitable donor, when more than one family member is available, are also addressed.

  8. Limb Preservation With Isolated Limb Infusion for Locally Advanced Nonmelanoma Cutaneous and Soft-Tissue Malignant Neoplasms

    PubMed Central

    Turaga, Kiran K.; Beasley, Georgia M.; Kane, John M.; Delman, Keith A.; Grobmyer, Stephen R.; Gonzalez, Ricardo J.; Letson, G. Douglas; Cheong, David; Tyler, Douglas S.; Zager, Jonathan S.

    2015-01-01

    Objective To demonstrate the efficacy of isolated limb infusion (ILI) in limb preservation for patients with locally advanced soft-tissue sarcomas and nonmelanoma cutaneous malignant neoplasms. Background Locally advanced nonmelanoma cutaneous and soft-tissue malignant neoplasms, including soft-tissue sarcomas of the extremities, can pose significant treatment challenges. We report our experience, including responses and limb preservation rates, using ILI in cutaneous and soft-tissue malignant neoplasms. Methods We identified 22 patients with cutaneous and soft-tissue malignant neoplasms who underwent 26 ILIs with melphalan and actinomycin from January 1, 2004, through December 31, 2009, from 5 institutions. Outcome measures included limb preservation and in-field response rates. Toxicity was measured using the Wieberdink scale and serum creatinine phosphokinase levels. Results The median age was 70 years (range, 19-92 years), and 12 patients (55%) were women. Fourteen patients (64%) had sarcomas, 7 (32%) had Merkel cell carcinoma, and 1 (5%) had squamous cell carcinoma. The median length of stay was 5.5 days (interquartile range, 4-8 days). Twenty-five of the 26 ILIs (96%) resulted in Wieberdink grade III or less toxicity, and 1 patient (4%) developed grade IV toxicity. The median serum creatinine phosphokinase level was 127 U/L for upper extremity ILIs and 93 U/L for lower extremity ILIs. Nineteen of 22 patients (86%) underwent successful limb preservation. The 3-month in-field response rate was 79% (21% complete and 58% partial), and the median follow-up was 8.6 months (range, 1-63 months). Five patients underwent resection of disease after an ILI, of whom 80% are disease free at a median of 8.6 months. Conclusions Isolated limb infusion provides an attractive alternative therapy for regional disease control and limb preservation in patients with limb-threatening cutaneous and soft-tissue malignant neoplasms. Short-term response rates appear encouraging, yet

  9. Novel therapies in benign and malignant bone diseases.

    PubMed

    Rachner, Tilman D; Hadji, Peyman; Hofbauer, Lorenz C

    2012-06-01

    With an ageing population and improving cancer therapies, the two most common benign and malignant bone diseases, osteoporosis and bone metastases, will continue to affect an increasing number of patients. Our expanding knowledge of the molecular processes underlying these conditions has resulted in novel bone targets that are currently being explored in clinical trials. Clearly, the approval of denosumab, a monoclonal antibody directed against RANKL, has just marked the beginning of a new era for bone therapy with several additional new therapies lining up for clinical approval in the coming years. Potential agents targeting the osteoclast include cathepsin K, currently in phase 3 trials, and src inhibitors. Amongst anabolic agents, inhibitors of the Wnt-inhibitor sclerostin and dickkopf-1 are promising in clinical trials. Here, we will provide a comprehensive overview of the most promising agents currently explored for the treatment of bone diseases.

  10. Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma

    PubMed Central

    Jing, Xu-Quan; Zhou, Lei; Sun, Xin-Dong; Yu, Jin-Ming; Meng, Xue

    2016-01-01

    Abstract Malignant pleural mesothelioma (MPM) is a lethal disease with poor prognosis. The combination of cisplatin and pemetrexed has been confirmed as the standard of care for nonoperable MPM. Data have shown that the adoption of pemetrexed maintenance therapy (PMT) following first-line treatment appears extremely promising. We describe a 57-year-old man diagnosed as advanced MPM. We treated this patient with PMT after first-line cisplatin-based bevacizumab-containing chemotherapy and residual tumor disappeared after 6 course of PMT. A perfect response and a long progression-free survival (PFS) were reached with tumor mass disappearing and 14 months duration of PFS. This case suggests that adding bevacizumab to standard first-line chemotherapy is feasible and that PMT could be promising and useful for treating advanced MPM. We further entail a review of the literature on the first-line treatment, continuation maintenance therapy, switch maintenance therapy, and second-line treatment of patients with advanced MPM. PMID:27057918

  11. Aggression: the dominant psychological response in children with malignant disease.

    PubMed

    Kvist, S B; Rajantie, J; Kvist, M; Siimes, M A

    1991-06-01

    During the 11-yr. period of 1976 to 1986 leukemia or lymphoma treatment at the Children's Hospital, University of Helsinki was electively discontinued for the children in 90 different families. Of the 53 (59%) patients (mean age 6.4 yr. at diagnosis and 12.8 yr. at completion of questionnaires) who agreed to participate in the present study, 48 had acute lymphoblastic leukemia and five nonHodgkin lymphoma. Patients' and parents' impressions of the patients' psychological reactions during patients' prior chemotherapy were evaluated on parental and self-ratings. Also, knowledge of and presumed causes of the malignancy were studied. Patients' reactions of aggression, depression, eating disorders, hypersensitivity, phobic anxiety, death anxiety, and night terror were examined using factor analysis. Aggression, in the form of irritation and anger, was displayed more often by girls than by boys. Patients of families suffering from stress were prone to exhibit aggression in the form of mood changes, irritation, and anger. Patients with disease-related knowledge, as opposed to those less well informed, were less depressed. Discrepancies between parents' and patients' thoughts about the origin of the malignancy were noted.

  12. Fluorescence detection of premalignant, malignant, and micrometastatic disease using hexylpyropheophorbide

    NASA Astrophysics Data System (ADS)

    Furukawa, Kinya; Crean, David H.; Mang, Thomas S.; Kato, Harubumi; Dougherty, Thomas J.

    1995-03-01

    We investigated the in vivo fluorescence detection of premalignant and malignant lesions in carcinogen-induced tumors of the hamster buccal cheek pouch and micrometastases in rat lymph nodes using hexylpyropheophorbide-a (HPPH) at 0.5 mg/kg and He-Ne laser-induced fluorescence photometry. Time course studies of HPPH in hamster tumor model showed maximal relative fluorescence readings at 48 hours after i.p. injection in each stage (dysplasia: 0.35, papilloma: 0.58, squamous cell carcinoma: 1.04). Squamous cell carcinoma showed significantly greater fluorescence than papillomas and dysplasias at all time points (p < 0.01). Metastatic lymph nodes were significantly greater than normal lymph nodes at all time points (p < 0.01). Maximal fluorescence levels of normal lymph nodes were observed at 6 hours after i.v. injection. Metastatic lymph nodes still showed high fluorescence levels at 72 hours. Micrometastases showed fluorescence levels between the levels of metastatic and normal lymph nodes (normal: 0.40 < micrometastasis: 0.62 < metastasis: 0.75 at 48 hours after i.v. injection). The results demonstrated good correlation between fluorescence levels and histopathological developments at all time points. Therefore, HPPH may be a promising fluorophore for the detection of developing malignancies and occult disease.

  13. A phase I study of indoximod in patients with advanced malignancies

    PubMed Central

    Soliman, Hatem H.; Minton, Susan E.; Han, Hyo Sook; Ismail-Khan, Roohi; Neuger, Anthony; Khambati, Fatema; Noyes, David; Lush, Richard; Chiappori, Alberto A.; Roberts, John D.; Link, Charles; Vahanian, Nicholas N.; Mautino, Mario; Streicher, Howard; Sullivan, Daniel M.; Antonia, Scott J.

    2016-01-01

    Purpose Indoximod is an oral inhibitor of the indoleamine 2,3-dioxygenase pathway, which causes tumor-mediated immunosuppression. Primary endpoints were maximum tolerated dose (MTD) and toxicity for indoximod in patients with advanced solid tumors. Secondary endpoints included response rates, pharmacokinetics, and immune correlates. Experimental Design Our 3+3 phase I trial comprised 10 dose levels (200, 300, 400, 600, and 800 mg once/day; 600, 800, 1200, 1600, and 2000 mg twice/day). Inclusion criteria were measurable metastatic solid malignancy, age ≥18 years, and adequate organ/marrow function. Exclusion criteria were chemotherapy ≤ 3 weeks prior, untreated brain metastases, autoimmune disease, or malabsorption. Results In 48 patients, MTD was not reached at 2000 mg twice/day. At 200 mg once/day, 3 patients previously treated with checkpoint inhibitors developed hypophysitis. Five patients showed stable disease >6 months. Indoximod plasma AUC and Cmax plateaued above 1200mg. Cmax (∼12 μM at 2000 mg twice/day) occurred at 2.9 hours, and half-life was 10.5 hours. C reactive protein (CRP) levels increased across multiple dose levels. Conclusions Indoximod was safe at doses up to 2000 mg orally twice/day. Best response was stable disease >6 months in 5 patients. Induction of hypophysitis, increased tumor antigen autoantibodies and CRP levels were observed. PMID:27008709

  14. Clinical applications of recent molecular advances in urologic malignancies: no longer chasing a "mirage"?

    PubMed

    Netto, George J

    2013-05-01

    As our understanding of the molecular events leading to the development and progression of genitourologic malignancies, new markers of detection, prognostication, and therapy prediction can be exploited in the management of these prevalent tumors. The current review discusses the recent advances in prostate, bladder, renal, and testicular neoplasms that are pertinent to the anatomic pathologist. PMID:23574774

  15. Microenvironmental Effects of Cell Death in Malignant Disease.

    PubMed

    Gregory, Christopher D; Ford, Catriona A; Voss, Jorine J L P

    2016-01-01

    Although apoptosis is well recognized as a cell death program with clear anticancer roles, accumulating evidence linking apoptosis with tissue repair and regeneration indicates that its relationship with malignant disease is more complex than previously thought. Here we review how the responses of neighboring cells in the microenvironment of apoptotic tumor cells may contribute to the cell birth/cell death disequilibrium that provides the basis for cancerous tissue emergence and growth. We describe the bioactive properties of apoptotic cells and consider, in particular, how apoptosis of tumor cells can engender a range of responses including pro-oncogenic signals having proliferative, angiogenic, reparatory, and immunosuppressive features. Drawing on the parallels between wound healing, tissue regeneration and cancer, we propose the concept of the "onco-regenerative niche," a cell death-driven generic network of tissue repair and regenerative mechanisms that are hijacked in cancer. Finally, we consider how the responses to cell death in tumors can be targeted to provide more effective and long-lasting therapies. PMID:27558817

  16. Results of chest wall resection for recurrent or locally advanced breast malignancies.

    PubMed

    Veronesi, Giulia; Scanagatta, Paolo; Goldhirsch, Aron; Rietjens, Mario; Colleoni, Marco; Pelosi, Giuseppe; Spaggiari, Lorenzo

    2007-06-01

    Between 1998 and 2003 we observed 15 women who underwent full thickness chest wall resection (FTCWR) followed by plastic reconstruction for locally recurrent or primary breast cancer. Preoperative symptoms were: pain (5 patients), malodorous ulceration (3 patients), presence of tumour mass (4 patients) and thoracic deformity (2 patients). One patient was asymptomatic. Surgery was partial sternectomy with rib resection in 9 patients, rib resection alone in 5, and total sternectomy in one. No perioperative mortality or major morbidity occurred; minor complications occurred in 3 patients (20%). Five of the six surviving patients reported a positive overall outcome in a telephonic interview. Median overall and disease-free survival were 23.4 and 17.5 months, respectively. In conclusion, FTCWR is a safe procedure with low morbidity and mortality that can provide good symptoms palliation in patients with locally advanced breast malignancies, so it should be considered more often by interdisciplinary care providers in those patients who fail to respond to classic multimodality treatment.

  17. Addition of an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy improves survival in advanced malignancies.

    PubMed

    Lasalvia-Prisco, Eduardo; Goldschmidt, Pablo; Galmarini, Felipe; Cucchi, Silvia; Vázquez, Jesús; Aghazarian, Martha; Lasalvia-Galante, Eduardo; Golomar, Wilson; Gordon, William

    2012-12-01

    Studies have shown that cancer requires two conditions for tumor progression: cancer cell proliferation and an environment permissive to and conditioned by malignancy. Chemotherapy aims to control the number and proliferation of cancer cells, but it does not effectively control the two best-known conditions of the tumor-permissive environment: neoangiogenesis and tolerogenic immunity. Many malignant diseases exhibit poor outcomes after treatment with chemotherapy. Therefore, we investigated the potential benefits of adding an induction regimen of antiangiogenesis and antitumor immunity to chemotherapy in poor outcome disease. In a prospective, randomized trial, we included patients with advanced, unresectable pancreatic adenocarcinomas, non-small cell lung cancer, or prostate cancer. Two groups of each primary condition were compared: group 1 (G1), n = 30, was treated with the standard chemotherapy and used as a control, and group 2 (G2), n = 30, was treated with chemotherapy plus an induction regimen of antiangiogenesis and antitumor immunity. This induction regimen included a low dose of metronomic cyclophosphamide, a high dose of Cox-2 inhibitor, granulocyte colony-stimulating factor, a sulfhydryl (SH) donor, and a hemoderivative that contained autologous tumor antigens released from patient tumors into the blood. After treatment, the G2 group demonstrated significantly longer survival, lower blood level of neoangiogenesis and immune-tolerance mediators, and higher blood levels of antiangiogenesis and antitumor immunity mediators compared with the G1 group. Toxicity and quality of life were not significantly different between the groups. In conclusion, in several advanced malignancies of different primary localizations, an increase in survival was observed by adding an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy.

  18. Related and unrelated nonmyeloablative hematopoietic stem cell transplantation for malignant diseases.

    PubMed

    Georges, George E; Maris, Michael; Sandmaier, Brenda M; Malone, David G; Feinstein, Lyle; Niederweiser, Dietger; Shizuru, Judith A; McSweeney, Peter A; Chauncey, Thomas R; Agura, Edward; Little, Marie-Trse; Sahebi, Firoozeh; Hegenbart, Ute; Pulsipher, Michael A; Bruno, Benedetto; Forman, Stephen; Woolfrey, Ann E; Radich, Jerald P; Blume, Karl G; Storb, Rainer

    2002-08-01

    Patients with advanced hematological malignancies ineligible for conventional myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) due to advanced age or medical contraindications were enrolled in multi-center study to investigate the safety and efficacy of nonmyeloablative HSCT using a 2 Gy total body irradi ation (TBI)-based regimen. A total of 192 patients (median age 55) were treated with HLA-matched sibling peripheral blood stem cell (PBSC) grafts, and 63 patients (median age 53) received a 10 of 10 HLA-antigen matched unrelated donor (URD) HSCT (PBSC graft, n = 48; marrow graft, n = 15). Diagnoses included multiple myeloma (n = 61), myelodysplastic syndrome (n = 55), chronic myeloid leukemia (n = 31), non-Hodgkin lymphoma (n = 31), acute myeloid leukemia (n = 28), chronic lymphocytic leukemia (n = 24), Hodgkin Disease (n = 14). The conditioning regimen was fludarabine 30 mg/m2/d x 3 days and 2 Gy TBI. Ninety-five related HSCT patients received 2 Gy TBI without fludarabine. Postgrafting immunosuppression was combined mycophenolate mofetil an cyclosporine. Transplants were well tolerated with a median of 0 days of hospitalization in the first 60 days for eligible patients. For related HSCT recipients, median follow-up was 289 (100-1,188) days. Nonfatal graft rejection occurred in 6.8%. Of those with sustained engraftment, graft-versus-host disease (GVHD) occurred in 49% (33% grade II, 11% grade III, 5% grade IV). Day-100 non-relapse mortality was 6%. Overall, 59% (114/192) of patients were alive. The relapse/disease progression mortality was 18%, and non-relapse mortality was 22%. The projecte 2-year survival and progression-free survival were 50% and 40%. For the URD HSCT recipients, median follow-up was 190 (100-468) days. Graft rejection occurred in 27% (17/63) of patients, mostly in recipients of marrow grafts (9/15). Acute GVHD occurred in 63% (50% grade II, 13% grade III) of 46 engrafted patients. Chronic GVHD requiring therapy occurred

  19. Advanced malignant solitary fibrous tumor in pelvis responding to radiation therapy.

    PubMed

    Kawamura, Shinobu; Nakamura, Takafumi; Oya, Takeshi; Ishizawa, Shin; Sakai, Yuta; Tanaka, Tomonori; Saito, Shigeru; Fukuoka, Junya

    2007-04-01

    Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm that is benign in most cases. Although SFT was first recognized to arise only in the pleura, recent reports indicate that SFT can involve a wide range of anatomical sites. To date, 17 cases of pelvic SFT have been reported. Herein is reported a case of a 74-year-old woman with a giant malignant SFT in the pelvis. Along with massive invasion to adjacent organs and multiple lung metastases detected on radiography, biopsy from the tumor through the vaginal wall showed malignant looking spindle-cell neoplasm with increased cellularity, areas of necrosis, and high mitotic activity (5/10 high-power fields). Immunohistochemically, the tumor cells were diffusely and strongly positive for CD34, CD99, and bcl-2. Based on pathological features and clinical presentation, diagnosis of malignant SFT was made. The patient received systemic and the intra-arterial chemotherapy followed by whole pelvic radiation therapy (50 Gy). Initial chemotherapies failed to control the tumor. Afterwards, improvement was observed radiologically and pathologically in the 12 months' follow up after the radiation therapy. This is the first report related to therapeutic remarks on advanced malignant SFT.

  20. Are patients with inflammatory eye disease treated with systemic immunosuppressive therapy at increased risk of malignancy?

    PubMed Central

    2013-01-01

    The purpose of this study is to review the literature on the risk of malignancy in patients with inflammatory eye disease (IED) treated with systemic immunosuppressive (IS) therapy. Relevant databases in transplant medicine, autoimmune diseases and literature regarding uveitis and scleritis were reviewed. Literature with regards systemic IS therapy in transplant recipients and patients with autoimmune diseases revealed a significant increase in malignancies, especially non-melanocytic skin cancers and lymphomas. Studies of patients with IED were limited in number and scope, with no studies adequately evaluating the incidence of malignancy in these patients. Difficulties associated with the evaluation of the risk of malignancy associated with IS therapy in patients with IED include the heterogeneity of the disease and treatment regimens as well as the low frequency of IED, its variable severity and the lack of adequate long-term follow-up studies. Systemic IS therapy is an important therapeutic option in the treatment of patients with severe IED. A well-designed, comprehensive, multi-centre long-term follow-up study is required to evaluate the risk of malignancy in patients with specific IED diseases treated with defined systemic IS therapy. Until such evidence is available, we recommend the adoption of preventative strategies to help minimise the risk of malignancy in such patients. PMID:23724805

  1. A case-control study of malignant and non-malignant respiratory disease among employees of a fiberglass manufacturing facility.

    PubMed Central

    Chiazze, L; Watkins, D K; Fryar, C

    1992-01-01

    A case-control study was conducted to determine the influence of non-workplace factors on risk of respiratory disease among workers at the Owens-Corning Fiberglas plant in Newark, Ohio. Cases and controls were drawn from a historical cohort mortality study conducted on behalf of the Thermal Insulation Manufacturers Association (TIMA) of workers employed at Newark for at least one year between 1 January 1940 and 31 December 1963 and followed up to the end of 1982. The TIMA study reported a statistically significant increase in respiratory cancer (compared with national death rates). Interviews were completed for 144 lung cancer cases and 299 matching controls and 102 non-malignant respiratory disease cases and 201 matching controls. Unadjusted odds ratios (ORs) were used to assess the association between lung cancer or non-malignant respiratory disease and birthplace, education, income, marital state, smoking with a duration of six months or more, age at which smoking first started, and duration of smoking. Only the smoking variables were statistically significant. For lung cancer, of the variables entered into a conditional logistic regression model, only the smoking OR of 23.4 (95% CI 3.2-172.9) was statistically significant. For non-malignant respiratory disease no variables entered into the final model were statistically significant. Results of the interview portion of our case-control study clearly indicate that smoking is the most important non-workplace factor for risk of lung cancer in this group of workers. Smoking does not seem to play as important a part, however, for non-malignant respiratory disease. Prevalence of cigarette smoking at the Newark plant was estimated for birth cohorts by calendar year. Corresponding data for the United States were compiled from national smoking surveys. Prevalence of cigarette smoking for Newark in 1955 appears to be sufficiently greater than the corresponding United States data in 1955 to suggest that some of the

  2. ARSENIC AND SKIN LESION STATUS IN RELATION TO MALIGNANT AND NON-MALIGNANT LUNG DISEASE MORTALITY IN BANGLADESHI ADULTS

    PubMed Central

    Argos, Maria; Parvez, Faruque; Rahman, Mahfuzar; Rakibuz-Zaman, Muhammad; Ahmed, Alauddin; Hore, Samar Kumar; Islam, Tariqul; Chen, Yu; Pierce, Brandon L.; Slavkovich, Vesna; Olopade, Christopher; Yunus, Muhammad; Baron, John A.; Graziano, Joseph H.; Ahsan, Habibul

    2015-01-01

    Background Chronic arsenic exposure through drinking water is a public health problem affecting millions of people worldwide, including at least 30 million in Bangladesh. We prospectively investigated the associations of arsenic exposure and arsenical skin lesion status with lung disease mortality in Bangladeshi adults. Methods Data are from a population-based sample of 26,043 adults, with an average of 8.5 years of follow-up (220,157 total person-years). There were 156 non-malignant lung disease deaths and 90 lung cancer deaths ascertained through October 2013. We used Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals (CIs) for lung disease mortality. Results Creatinine-adjusted urinary total arsenic was associated with non-malignant lung disease mortality, with persons in the highest tertile of exposure having a 75% increased risk for mortality (95% CI=1.15–2.66) compared with those in the lowest tertile of exposure. Persons with arsenical skin lesions were at increased risk of lung cancer mortality (hazard ratio=4.53 [95% CI=2.82–7.29]) compared with those without skin lesions. Conclusions This prospective investigation of lung disease mortality, utilizing individual-level arsenic measures and skin lesion status, confirms a deleterious effect of ingested arsenic on mortality from lung disease. Further investigations should evaluate effects on the incidence of specific lung diseases, more fully characterize dose-response, and evaluate screening and biomedical interventions to prevent premature death among arsenic-exposed populations, particularly among those who may be most susceptible to arsenic toxicity. PMID:24802365

  3. Intercostal nerves block for mastectomy in two patients with advanced breast malignancy.

    PubMed

    Kolawole, Israel K; Adesina, Michael D; Olaoye, Iyiade O

    2006-03-01

    Regional anesthesia is recognized as an alternative to general anesthesia for modern breast cancer surgery. Various techniques of block have been described. Each has its unique problems. Regional anesthesia was chosen for simple mastectomy in two patients with advanced breast malignancy, due to compromised pulmonary status resulting from widespread malignant infiltration of both lungs. We used intercostal nerves block. The block was supplemented with an infraclavicular infiltration to interrupt the branches of the superficial cervical plexus that provide sensation to the upper chest wall and subcutaneous infiltration in the midline to block the nerve supply from the contralateral side. Anesthesia was generally effective and the operations were uneventful. Both patients and surgeons expressed satisfaction. We conclude that where patients have significant comorbidities that make general anesthesia undesirable, the use of intercostal nerves block remains a safe and reliable anesthetic option that allows the patient access to surgery for simple mastectomy.

  4. [Advance in Research of Angiotensin II and Its Receptor and Malignant Tumor].

    PubMed

    Sun, Lulu; Shi, Jian

    2016-09-20

    Angiotensin AngII, a linear small peptide,which is composed of eight amino acids, is the main effectors of renin-angiotensin systen (Renin-angiotensin system, RAS). AngII, a main biopolypeptide of the RAS, has important pathophysiologic in effects participating in cardiac hypertrophy, vascular cell proproliferation, inflammation and tissue remodeling through G-protein-coupled receptors. In recent years, Ang II can promote tumor cell proliferation, tumor vessel formation and inhibit the differentiation of the tumor cells. This suggests that inhibit the production of AngII or block its effect is expected to become a new measure for the treatment of malignant tumors. This article reviews the advances in research on the relationship between AngII and its receptor and malignant tumor in recent years. PMID:27666553

  5. Recent advances in oesophageal diseases.

    PubMed

    Al Dulaimi, David

    2014-01-01

    -quadrant biopsy protocol which may have led to an underestimation of BE prevalence. The review highlights an increasing incidence of esophageal adenocarcinoma in the West but unclear disease trend in Asia with inter-country variability. Similarly in Asian and Western countries BE is associated with the presence of hiatus hernia, advancing age, male gender, alcohol consumption, smoking, abdominal obesity and longer duration of gastro-esophageal reflux disease. The authors postulate that Helicobacter pylori infection, more prevalent in Asia than the West, may have a protective effect on BE. There is a need for larger, prospective studies to further clarify the disease pattern of BE in Asian countries. Clearly standardisation of the diagnostic process for BE is important to validate the differences in disease trends between Asian and Western countries. Kiadaliri AA. Gender and social disparities in esophagus cancer incidence in Iran, 2003-2009: a time trend province-level study.Asian Pac J Cancer Prev 2014;15(2):623-7 Esophageal cancer (EC) is a major cause of morbidity and mortality particuarly in Iran where the incidence rate exceeds the global average. An understanding of the factors influencing the province-specific incidence of EC in Iran is important to inform disease-prevention strategies and address health inequalities. This ecological study used cancer registry data to investigate the relationship between gender and social class and the incidence of EC in Iran at province-level between 2003 and 2009. The age standardised incidence rates (ASIR) of EC were greatest in the Northern provinces of Iran, specifically Razavi Khorasan in males and Kordestan in females. Overall the EC incidence did not significantly differ according to gender. Interestingly, during the study period the ASIR increased by 4.6% per year in females (p=0.08) and 6.5% per year in males (p=0.02). This may reflect increasing rates of establised risk factors for EC including obsesity and gastro

  6. Recent advances in oesophageal diseases.

    PubMed

    Al Dulaimi, David

    2014-01-01

    -quadrant biopsy protocol which may have led to an underestimation of BE prevalence. The review highlights an increasing incidence of esophageal adenocarcinoma in the West but unclear disease trend in Asia with inter-country variability. Similarly in Asian and Western countries BE is associated with the presence of hiatus hernia, advancing age, male gender, alcohol consumption, smoking, abdominal obesity and longer duration of gastro-esophageal reflux disease. The authors postulate that Helicobacter pylori infection, more prevalent in Asia than the West, may have a protective effect on BE. There is a need for larger, prospective studies to further clarify the disease pattern of BE in Asian countries. Clearly standardisation of the diagnostic process for BE is important to validate the differences in disease trends between Asian and Western countries. Kiadaliri AA. Gender and social disparities in esophagus cancer incidence in Iran, 2003-2009: a time trend province-level study.Asian Pac J Cancer Prev 2014;15(2):623-7 Esophageal cancer (EC) is a major cause of morbidity and mortality particuarly in Iran where the incidence rate exceeds the global average. An understanding of the factors influencing the province-specific incidence of EC in Iran is important to inform disease-prevention strategies and address health inequalities. This ecological study used cancer registry data to investigate the relationship between gender and social class and the incidence of EC in Iran at province-level between 2003 and 2009. The age standardised incidence rates (ASIR) of EC were greatest in the Northern provinces of Iran, specifically Razavi Khorasan in males and Kordestan in females. Overall the EC incidence did not significantly differ according to gender. Interestingly, during the study period the ASIR increased by 4.6% per year in females (p=0.08) and 6.5% per year in males (p=0.02). This may reflect increasing rates of establised risk factors for EC including obsesity and gastro

  7. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods.

    PubMed

    Ahmed, Rafay; Oborski, Matthew J; Hwang, Misun; Lieberman, Frank S; Mountz, James M

    2014-01-01

    Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12-15 months for glioblastomas and 2-5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies, and importantly, for facilitating patient management, sparing patients from weeks or months of toxicity and ineffective treatment. This review will present an overview of epidemiology, molecular pathogenesis and current advances in diagnoses, and management of malignant gliomas.

  8. Genetic susceptibility to malignant diseases--ethical issues. Minireview.

    PubMed

    Munzarová, M

    2002-01-01

    Ethical problems connected with genetic testing with the intention of the measurement of the susceptibility or predisposition to malignant tumors are presented (respect for autonomy, beneficence, nonmaleficence, confidentiality, privacy, veracity and truth-telling, informed consent, right to know, right not to know, informational self-determination, etc.). Various aspects dealing with ethics of screening and research projects involving human subjects are discussed as well.

  9. NASA Bioreactors Advance Disease Treatments

    NASA Technical Reports Server (NTRS)

    2009-01-01

    the body. Experiments conducted by Johnson scientist Dr. Thomas Goodwin proved that the NASA bioreactor could successfully cultivate cells using simulated microgravity, resulting in three-dimensional tissues that more closely approximate those in the body. Further experiments conducted on space shuttle missions and by Wolf as an astronaut on the Mir space station demonstrated that the bioreactor s effects were even further expanded in space, resulting in remarkable levels of tissue formation. While the bioreactor may one day culture red blood cells for injured astronauts or single-celled organisms like algae as food or oxygen producers for a Mars colony, the technology s cell growth capability offers significant opportunities for terrestrial medical research right now. A small Texas company is taking advantage of the NASA technology to advance promising treatment applications for diseases both common and obscure.

  10. Degos diseasemalignant atrophic papulosis or cutaneointestinal lethal syndrome: rarity of the disease

    PubMed Central

    Pirolla, Eduardo; Fregni, Felipe; Miura, Irene K; Misiara, Antonio Carlos; Almeida, Fernando; Zanoni, Esdras

    2015-01-01

    Background Degos disease is a very rare syndrome with a rare type of multisystem vasculopathy of unknown cause that affects the skin, gastrointestinal tract, and central nervous system. Other organs such as the kidneys, lungs, pleura, liver, heart, and eyes, can also be involved. Objective To highlight the incidence of Degos disease with regard to age and sex, discuss the necessity of its accurate and early diagnosis, and demonstrate the most current techniques for its diagnosis; to discuss whether early therapeutic intervention can impact patient prognosis; and to present a literature review about this disease. Design With a retrospective, observational, nonrandomized trial, we described the evolution of the different forms of Degos disease and referenced the literature. Data sources Research on rare documented cases in the literature, including two cases of potentially lethal form of the disease involving the skin and gastrointestinal system and, possibly, the lungs, kidneys, and central nervous system. A case of the benign form of the disease involving the skin was observed by the authors. Main outcome measures Differences between outcomes in patients with the cutaneointestinal form and skin-only form of the disease. There was one fatal outcome. We reviewed possible new approaches to diagnosis and treatment. Results The study demonstrated the rapid evolution of the aggressive and malignant form of the disease. It also described newly accessible Phase I diagnostic tools being currently researched as well as new therapeutic approaches. Limitation The rarity of the disease, with only eleven cases throughout the literature. Conclusion The gastrointestinal form of Degos disease can be lethal. Its vascular etiology has finally been confirmed; however, new and more accurate early diagnostic modalities need to be developed. There are new therapeutic possibilities, but the studies of them are still in the early stages and have not yet shown the full effectiveness of

  11. Pediatric allo-SCT for malignant and non-malignant diseases: impact on health-related quality of life outcomes.

    PubMed

    Oberg, J A; Bender, J G; Morris, E; Harrison, L; Basch, C E; Garvin, J H; Sands, S A; Cairo, M S

    2013-06-01

    The objective of this study was prospectively to investigate the health-related quality of life (HRQOL) of 80 pediatric recipients of allo-SCT for malignant and non-malignant diseases. The PedsQL 4.0 was used to assess self-reported physical, emotional and social functioning of children 5 years old once, pre-allo-SCT and on days +100, +180, +365 and +730. Emotional and social functioning was stable pre-to-post-allo-SCT and comparable to the normative sample (P>0.05), and physical functioning was 17 points lower pre-allo-SCT (P0.01) with improved scores equivalent to the norms by day +730. Lower physical scores were reflected by 50-54% of children reporting difficulties with movement, strength, pain and fatigue. At baseline, children ages 5-7 reported lower social functioning (P<0.05) and patients with non-malignant disease reported better physical functioning (P<0.05). Emotional functioning in ages 8-12 improved over time (P<0.05). More than 50% of the participants were minority and their HRQOL was similar to non-minority participants. Physical functioning significantly improved for recipients of reduced-toxicity conditioning (P0.01), significantly worsened for patients with chronic GVHD (cGVHD; P<0.05), and significantly decreased in recipients of matched-unrelated donor transplant who developed cGVHD (P<0.05). Multidisciplinary efforts are necessary to identify and support pediatric patients' physical needs to improve functional outcomes.

  12. Analgesia for patients with advanced disease: 2

    PubMed Central

    Hall, E; Sykes, N

    2004-01-01

    The first article in this series explored epidemiology and patterns of pain in advanced disease, non-pharmacological treatments, and the use of opioids to manage pain. This second article examines the use of non-opioid drugs and anaesthetic interventions for pain relief in advanced disease. It also discusses an approach to managing analgesia in dying patients and finally looks at future developments. PMID:15082837

  13. Precision oncology for patients with advanced cancer: the challenges of malignant snowflakes

    PubMed Central

    Kurzrock, Razelle; Giles, Francis J

    2015-01-01

    Precision oncology implies customizing treatment to the unique molecular and biologic characteristics of each individual and their cancer. Its implementation is being facilitated by remarkable technological advances in genomic sequencing, as well as the increasing availability of targeted and immunotherapeutic drugs. Yet, next generation sequencing may be a disruptive technology in that its results suggest that classic paradigms for clinical research and practice are a poor fit with the complex reality encountered in metastatic malignancies. Indeed, it is evident that advanced tumors have heterogeneous molecular landscapes that mostly differ between patients. Traditional modes of clinical research/practice are drug centered, with a strategy of finding commonalities between patients so that they can be grouped together and treated similarly. However, if each patient with metastatic cancer has a unique molecular portfolio, a new patient-centered, N-of-one approach that utilizes individually tailored treatment is needed. PMID:26030337

  14. Gaucher disease and comorbidities: B-cell malignancy and parkinsonism.

    PubMed

    Cox, Timothy M; Rosenbloom, Barry E; Barker, Roger A

    2015-07-01

    Data emerging from the International Collaborative Gaucher Group (ICGG) Gaucher Registry together with other contemporary clinical surveys have revealed a close association between Gaucher disease and non-Hodgkin's B-cell lymphoma and myeloma and Gaucher disease and Parkinson's disease. Several possible explanations for increased B-cell proliferation and neoplasia in Gaucher disease have been proposed, including the possible influence of sphingosine (derived from the extra lysosomal metabolism of glucosylceramide), gene modifiers, splenectomy and immune system deregulation induced by cytokines, chemokines, and hydrolases released from Gaucher cells. Parkinson's disease is frequently seen in the otherwise-healthy relatives of Gaucher disease patients leading to the finding that GBA mutations represent a genetic risk factor for Parkinson's disease. The mechanism of the association between GBA mutations and Parkinson's disease has yet to be elucidated but the pathogenesis appears distinct from that of Gaucher disease. Several pathogenic pathways have been proposed including lysosomal and/or mitochondrial dysfunction. The effect of Gaucher disease specific therapies on the incidence of cancer or Parkinson's disease are not clear and will likely be evaluated in future ICGG Gaucher Registry studies. PMID:26096744

  15. Second primary malignancies among patients with myeloma-related-diseases in the KMF database.

    PubMed

    Kosugi, Satoru; Shibayama, Hirohiko; Nakatani, Eiji; Kida, Toru; Ohta, Kensuke; Kaneko, Hidemi; Yagi, Hideo; Tanaka, Hirokazu; Fuchida, Shin-Ichi; Nakaya, Aya; Kobayashi, Masayuki; Kuroda, Junya; Kamitsuji, Yuri; Uoshima, Nobuhiko; Adachi, Yoko; Tsudo, Mitsuru; Shimazaki, Chihiro; Nomura, Shosaku; Hino, Masayuki; Matsumura, Itaru; Taniwaki, Masashi; Kanakura, Yuzuru; Takaori-Kondo, Akifumi

    2016-07-01

    The incidence of second primary malignancies (SPMs) in Japanese patients with myeloma or myeloma-related diseases was studied by using the Kansai Myeloma Forum (KMF) database registered from November 2012 to March 2015. We studied 1,571 cases. Hematologic malignancies were documented in 10 patients, and solid tumors in 36 during this period. The cumulative 5-year incidence was estimated to be 1.0% for hematological malignancies and 3.7% for solid tumors. In the patients with smoldering myeloma or MGUS without treatment, solid tumors but not hematologic malignancies developed, though the cumulative incidence of each malignancy did not differ significantly from that in patients receiving treatment. Although statistical analysis showed that treatment with melphalan, bortezomib, lenalidomide, or thalidomide had no effect on the occurrence of hematological malignancies, lenalidomide administration was more frequent in the patients with solid tumors. To evaluate the SPMs in myeloma or myeloma-related diseases more accurately, accumulation of a larger number of patients and longer observation are needed. PMID:27498726

  16. Advances in inflammatory bowel diseases in children.

    PubMed

    Michail, S; Ramsy, M; Soliman, E

    2012-06-01

    Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition that burdens the lives of many children around the world. It is characterized by chronic gastrointestinal inflammation. Crohn's disease (CD), ulcerative colitis and IBD-unknown are the three types of this disease. The management of children with inflammatory bowel disease is complex and requires skill, knowledge and experience with current advances in the field. Over the past several years, there have been a number of achievements and progress made in the care and management of this disorder. The diagnostic tools have greatly improved. The therapeutic armamentarium has expanded. The genetics of IBD has become more detailed and the role of the gut microbiome has been better defined. The evolution of biological agents has revolutionized the way we approach this disease. This review highlights the recent advances in pediatric inflammatory bowel disease and provides an overview for clinicians caring for children with this disorder. PMID:22555319

  17. Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas.

    PubMed

    Chaichana, Kaisorn L; Pinheiro, Leon; Brem, Henry

    2015-03-01

    Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy. PMID:25853310

  18. Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas

    PubMed Central

    Chaichana, Kaisorn L; Pinheiro, Leon; Brem, Henry

    2015-01-01

    Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy. PMID:25853310

  19. Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas.

    PubMed

    Chaichana, Kaisorn L; Pinheiro, Leon; Brem, Henry

    2015-03-01

    Malignant gliomas, including glioblastoma and anaplastic astrocytomas, are characterized by their propensity to invade surrounding brain parenchyma, making curative resection difficult. These tumors typically recur within two centimeters of the resection cavity even after gross total removal. As a result, there has been an emphasis on developing therapeutics aimed at achieving local disease control. In this review, we will summarize the current developments in the delivery of local therapeutics, namely direct injection, convection-enhanced delivery and implantation of drug-loaded polymers, as well as the application of these therapeutics in future methods including microchip drug delivery and local gene therapy.

  20. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases.

    PubMed

    Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

    2016-01-01

    Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent.

  1. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases

    PubMed Central

    Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

    2016-01-01

    Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent. PMID:27200087

  2. Circulating HMGB1 and RAGE as Clinical Biomarkers in Malignant and Autoimmune Diseases

    PubMed Central

    Pilzweger, Christin; Holdenrieder, Stefan

    2015-01-01

    High molecular group box 1 (HMGB1) is a highly conserved member of the HMG-box-family; abundantly expressed in almost all human cells and released in apoptosis; necrosis or by activated immune cells. Once in the extracellular space, HMGB1 can act as a danger associated molecular pattern (DAMP), thus stimulating or inhibiting certain functions of the immune system; depending on the “combinatorial cocktail” of the surrounding milieu. HMGB1 exerts its various functions through binding to a multitude of membrane-bound receptors such as TLR-2; -4 and -9; IL-1 and RAGE (receptor for advanced glycation end products); partly complex-bound with intracellular fragments like nucleosomes. Soluble RAGE in the extracellular space, however, acts as a decoy receptor by binding to HMGB1 and inhibiting its effects. This review aims to outline today’s knowledge of structure, intra- and extracellular functions including mechanisms of release and finally the clinical relevance of HMGB1 and RAGE as clinical biomarkers in therapy monitoring, prediction and prognosis of malignant and autoimmune disease. PMID:26854151

  3. LFA-1 expression on exocrine glands as a potential novel marker of malignant disease.

    PubMed

    Futagami-Mizoguchi, E; Yamada, A; Mizoguchi, A; Imai, Y; Yokoyama, M M

    1993-09-01

    The lymphocyte function associated antigen 1 has been found only on leukocytes and lymphoid tissues; however, the expression of lymphocyte function associated antigen 1 on nonhematopoietic cells has not been reported previously. In this study, immunohistochemical expression of lymphocyte function associated antigen 1 was examined on various tissues from 35 patients with malignant diseases and 36 patients with benign diseases including benign tumors. The expression of lymphocyte function associated antigen 1 was found on various exocrine tissues (eg, gastric glands, bronchial epithelium, alveolar epithelium, duodenal glands, bile ducts, pancreatic acini, and salivary glands) uninvolved by tumor in patients with malignant diseases. Localization of lymphocyte function associated antigen 1 was limited to the exocrine glands and differed from tissue-infiltrating leukocytes. The expression of lymphocyte function associated antigen 1 on exocrine tissues was confirmed in all 35 cases of malignant diseases that were examined. These included a wide spectrum of carcinomas and hematopoietic tumors. In contrast, none of the 36 cases with benign diseases examined expressed lymphocyte function associated antigen 1 on their exocrine glands. These results indicate a strong correlation between lymphocyte function associated antigen 1 expression on exocrine glands and malignant disease. The expression of lymphocyte function associated antigen 1 on nonhematopoietic cells was further confirmed in nonhematopoietic cell lines. Two of 19 nonhematopoietic cell lines (MKN45 and PANC-1; exocrine gland cell lines) examined expressed lymphocyte function associated antigen 1 on both cell surface and cytoplasm. These results suggested that immunohistochemically defined lymphocyte function associated antigen 1 molecules on nontumorous exocrine gland cells are a potential marker for the presence of malignant diseases.

  4. Advances in pleural disease management including updated procedural coding.

    PubMed

    Haas, Andrew R; Sterman, Daniel H

    2014-08-01

    Over 1.5 million pleural effusions occur in the United States every year as a consequence of a variety of inflammatory, infectious, and malignant conditions. Although rarely fatal in isolation, pleural effusions are often a marker of a serious underlying medical condition and contribute to significant patient morbidity, quality-of-life reduction, and mortality. Pleural effusion management centers on pleural fluid drainage to relieve symptoms and to investigate pleural fluid accumulation etiology. Many recent studies have demonstrated important advances in pleural disease management approaches for a variety of pleural fluid etiologies, including malignant pleural effusion, complicated parapneumonic effusion and empyema, and chest tube size. The last decade has seen greater implementation of real-time imaging assistance for pleural effusion management and increasing use of smaller bore percutaneous chest tubes. This article will briefly review recent pleural effusion management literature and update the latest changes in common procedural terminology billing codes as reflected in the changing landscape of imaging use and percutaneous approaches to pleural disease management.

  5. [Palliative surgery for malignant bowel obstruction in patients with advanced and recurrent gastroenterological cancer].

    PubMed

    Kitani, Kotaro; Yukawa, Masao; Fujiwara, Yoshinori; Tsujie, Masanori; Hara, Joji; Ikeda, Mitsunori; Sato, Katsuaki; Isono, Sayuri; Kawai, Kenji; Miura, Ken; Watatani, Masahiro; Inoue, Masatoshi

    2013-11-01

    We report the outcomes of palliative surgery for the treatment of malignant bowel obstruction in patients with advanced gastroenterological cancer. We studied 20 patients who had undergone palliative surgery over 3 years. We analyzed the clinical findings, surgical procedure, postoperative clinical course, and prognosis. The origin of the patients was colorectal cancer( 9 cases), gastric cancer( 4 cases), uterine cancer( 3 cases), pancreatic cancer( 2 cases), bladder( 1 case), and anal cancer (1 case). Small bowel obstruction was noted in 8 cases and colorectal obstruction was noted in 14 cases. Colostomy was performed in 13 cases, resection and reconstruction were performed in 6 cases, and bypass was performed in 4 cases. Ninety percent of the patients were able to eat solid food following the surgery, but 20% of the patients were forced to have bowel obstruction. The median survival time after palliative surgery was 3 (range, 0-15) months, and 6 patients (30%) died within 2 months. We concluded that palliative surgery for the treatment of malignant bowel obstruction could improve the patients' quality of life. The decision for performing palliative surgery should be made while considering the patient's prognosis, wishes, and potential for symptom improvement. PMID:24393893

  6. 78 FR 76507 - Revised Medical Criteria for Evaluating Cancer (Malignant Neoplastic Diseases)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-17

    ... comments at the time because they were outside the scope of the 2008 NPRM. \\1\\ 74 FR 51229. \\2\\ 73 FR 22871... commonly used term, and more recognized by the lay public and by health care professionals. The phrase ``malignant neoplastic disease'' is a term used almost exclusively, although infrequently, by health...

  7. PELVIC ACTINOMYCOSIS MIMICKING A LOCALLY ADVANCED PELVIC MALIGNANCY--CASE REPORT.

    PubMed

    Velenciuc, Natalia; Velenciuc, I; Makkai Popa, S; Roată, C; Ferariu, D; Luncă, S

    2016-01-01

    We present the case of a former user of an intrauterine contraceptive device (IUD) for 10 years, diagnosed with a bulky, fixed pelvic tumor involving the internal genital organs and the recto sigmoid, causing luminal narrowing of the rectum, interpreted as locally advanced pelvic malignancy, probably of genital origin. Intraoperatively, a high index of suspicion made us collect a sample from the fibrous wall of the tumor mass, large Actinomyces colonies were thus identified. Surgery consisted in debridement, removal of a small amount of pus and appendectomy, thus avoiding a mutilating and useless surgery. Specific antibiotic therapy was administered for 3 months, with favorable postoperative and long-term outcomes. Pelvic actinomycosis should always be considered in the differential diagnosis of pelvic tumors in women using an IUD. The association of long-term antibiotic treatment is essential to eradicate the infection and prevent relapses. PMID:27483724

  8. Critical methodological factors in diagnosing minimal residual disease in hematological malignancies using quantitative PCR.

    PubMed

    Nyvold, Charlotte Guldborg

    2015-05-01

    Hematological malignancies are a heterogeneous group of cancers with respect to both presentation and prognosis, and many subtypes are nowadays associated with aberrations that make up excellent molecular targets for the quantification of minimal residual disease. The quantitative PCR methodology is outstanding in terms of sensitivity, specificity and reproducibility and thus an excellent choice for minimal residual disease assessment. However, the methodology still has pitfalls that should be carefully considered when the technique is integrated in a clinical setting.

  9. Prognostic factors and disease-specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden.

    PubMed

    Simberg-Danell, Caroline; Lyth, Johan; Månsson-Brahme, Eva; Frohm-Nilsson, Margareta; Carstensen, John; Hansson, Johan; Eriksson, Hanna

    2016-08-01

    Little is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease-specific survival among first- and second-generation immigrants in Sweden. This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM, 1990-2007. Data were linked to nationwide, population-based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status, stage and CMM prognosis, respectively. After adjustments for confounders, first generation immigrants from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish-born patients [Stage II vs. I: Odds ratio (OR) = 2.37, 95% CI = 1.61-3.50. Stage III-IV vs I: OR = 2.40, 95% CI = 1.08-5.37]. The ORs of stage II-IV versus stage I disease were increased among men (OR = 1.9; 95% CI = 1.1-3.3; p = 0.020), and women (OR = 4.8; 95% CI = 2.6-9.1; p < 0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-born patients. The CMM-specific survival was significantly decreased among women from former Yugoslavia versus Swedish-born women [hazard ratio (HR)=2.2; 95% CI = 1.1-4.2; p = 0.043]. After additional adjustments including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish-born patients were observed. In conclusion, a worse CMM-specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve the CMM prognosis. PMID:27004457

  10. Outcome of stenting in biliary and pancreatic benign and malignant diseases: A comprehensive review

    PubMed Central

    Mangiavillano, Benedetto; Pagano, Nico; Baron, Todd H; Luigiano, Carmelo

    2015-01-01

    Endoscopic stenting has become a widely method for the management of various malignant and benign pancreatico-biliary disorders. Biliary and pancreatic stents are devices made of plastic or metal used primarily to establish patency of an obstructed bile or pancreatic duct and may also be used to treat biliary or pancreatic leaks, pancreatic fluid collections and to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis. In this review, relevant literature search and expert opinions have been used to evaluate the outcome of stenting in biliary and pancreatic benign and malignant diseases. PMID:26290631

  11. Burden of metastatic bone disease from genitourinary malignancies.

    PubMed

    Mulders, Peter F; Abrahamsson, Per-Anders; Bukowski, Ronald M

    2010-11-01

    Bone metastases are common among patients with stage IV genitourinary cancers. Most patients with bone metastases develop at least one debilitating and potentially life-limiting skeletal-related event. These events are associated with increased medical expenses and decreased quality of life. Current guidelines recommend screening for bone metastases in men with high-risk prostate cancer, but guidance for screening and treatment of bone metastases from genitourinary cancers varies by country and setting. Several bisphosphonates have been evaluated in the advanced genitourinary cancer setting. Zoledronic acid has demonstrated efficacy in significantly reducing the risk of skeletal-related events in patients with bone metastases from a broad range of solid tumors including prostate, renal and bladder cancers, and is recommended for preserving bone health.

  12. Pancreaticobiliary reflux as a high-risk factor for biliary malignancy: Clinical features and diagnostic advancements

    PubMed Central

    Sugita, Reiji

    2015-01-01

    Pancreaticobiliary junction is composed of complex structure with which biliary duct and pancreatic duct assemble and go out into the ampulla of Vater during duodenum wall surrounding the sphincter of Oddi. Although the sphincter of Oddi functionally prevents the reflux of pancreatic juice, pancreaticobiliary reflux (PBR) occurs when function of the sphincter of Oddi halt. The anatomically abnormal junction is termed pancreaticobiliary maljunction (PBM) and is characterized by pancreatic and bile ducts joining outside of the duodenal wall. PBM is an important anatomical finding because many studies have revealed that biliary malignancies are related due to the carcinogenetic effect of the pancreatic back flow on the biliary mucosa. On the other hand, several studies have been published on the reflux of pancreatic juice into the bile duct without morphological PBM, and the correlation of such cases with biliary diseases, especially biliary malignancies, is drawing considerable attention. Although it has long been possible to diagnose PBM by various imaging modalities, PBR without PBM has remained difficult to assess. Therefore, the pathological features of PBR without PBM have not been yet fully elucidated. Lately, a new method of diagnosing PBR without PBM has appeared, and the features of PBR without PBM should soon be better understood. PMID:26167246

  13. The evolving use of arsenic in pharmacotherapy of malignant disease.

    PubMed

    Kritharis, Athena; Bradley, Thomas P; Budman, Daniel R

    2013-06-01

    For more than 2,000 years, arsenic and its derivatives have shown medical utility. Owing to the toxicities and potential carcinogenicity of arsenicals, their popularity has fluctuated. The exact mechanism of action of therapeutic arsenic is not well characterized but likely to involve apoptosis, generation of reactive oxygen species, inhibition of intracellular transduction pathways, and cell functions. Arsenic trioxide has received approval for use in patients with relapsed acute promyelocytic leukemia for remission induction. Arsenic has additionally shown activity in a range of solid tumors, myelodysplastic syndrome, multiple myeloma, and in autoimmune diseases. The following is a review of the history of arsenic, its cellular metabolism, pharmacology, genetic basis of disposition, associated toxicities, and clinical efficacy.

  14. The evolving use of arsenic in pharmacotherapy of malignant disease.

    PubMed

    Kritharis, Athena; Bradley, Thomas P; Budman, Daniel R

    2013-06-01

    For more than 2,000 years, arsenic and its derivatives have shown medical utility. Owing to the toxicities and potential carcinogenicity of arsenicals, their popularity has fluctuated. The exact mechanism of action of therapeutic arsenic is not well characterized but likely to involve apoptosis, generation of reactive oxygen species, inhibition of intracellular transduction pathways, and cell functions. Arsenic trioxide has received approval for use in patients with relapsed acute promyelocytic leukemia for remission induction. Arsenic has additionally shown activity in a range of solid tumors, myelodysplastic syndrome, multiple myeloma, and in autoimmune diseases. The following is a review of the history of arsenic, its cellular metabolism, pharmacology, genetic basis of disposition, associated toxicities, and clinical efficacy. PMID:23494203

  15. Advances in identifying beryllium sensitization and disease.

    PubMed

    Middleton, Dan; Kowalski, Peter

    2010-01-01

    Beryllium is a lightweight metal with unique qualities related to stiffness, corrosion resistance, and conductivity. While there are many useful applications, researchers in the 1930s and 1940s linked beryllium exposure to a progressive occupational lung disease. Acute beryllium disease is a pulmonary irritant response to high exposure levels, whereas chronic beryllium disease (CBD) typically results from a hypersensitivity response to lower exposure levels. A blood test, the beryllium lymphocyte proliferation test (BeLPT), was an important advance in identifying individuals who are sensitized to beryllium (BeS) and thus at risk for developing CBD. While there is no true "gold standard" for BeS, basic epidemiologic concepts have been used to advance our understanding of the different screening algorithms.

  16. Advances in Identifying Beryllium Sensitization and Disease

    PubMed Central

    Middleton, Dan; Kowalski, Peter

    2010-01-01

    Beryllium is a lightweight metal with unique qualities related to stiffness, corrosion resistance, and conductivity. While there are many useful applications, researchers in the 1930s and l940s linked beryllium exposure to a progressive occupational lung disease. Acute beryllium disease is a pulmonary irritant response to high exposure levels, whereas chronic beryllium disease (CBD) typically results from a hypersensitivity response to lower exposure levels. A blood test, the beryllium lymphocyte proliferation test (BeLPT), was an important advance in identifying individuals who are sensitized to beryllium (BeS) and thus at risk for developing CBD. While there is no true “gold standard” for BeS, basic epidemiologic concepts have been used to advance our understanding of the different screening algorithms. PMID:20195436

  17. Helicobacter pylori and non-malignant upper gastrointestinal diseases.

    PubMed

    Vasapolli, Riccardo; Malfertheiner, Peter; Kandulski, Arne

    2016-09-01

    Peptic ulcer disease (PUD) has been further decreased over the last decades along with decreasing prevalence of Helicobacter pylori-associated PUD. A delayed H. pylori eradication has been associated with an increased risk of rehospitalization for complicated recurrent peptic ulcer and reemphasized the importance of eradication especially in patients with peptic ulcer bleeding (PUB). PUB associated with NSAID/aspirin intake and H. pylori revealed an additive interaction in gastric pathophysiology which favors the "test-and-treat" strategy for H. pylori in patients with specific risk factors. The H. pylori-negative and NSAID-negative "idiopathic PUD" have been increasingly observed and associated with slower healing tendency, higher risk of recurrence, and greater mortality. Helicobacter pylori-associated dyspepsia has been further investigated and finally defined by the Kyoto consensus. Helicobacter pylori eradication therapy is advised as first option in this group of patients. Only in the case of symptom persistence or recurrence after eradication therapy, dyspeptic patients should be classified as functional dyspepsia (FD). There were few new data in 2015 on the role of H. pylori infection in gastroesophageal reflux disease (GERD), and in particular Barrett's esophagus. A lower prevalence of gastric atrophy with less acid output in patients with erosive esophagitis confirmed previous findings. In patients with erosive esophagitis, no difference was observed in healing rates neither between H. pylori-positive and H. pylori-negative patients nor between patients that underwent eradication therapy compared to patients without eradication. These findings are in line with the current consensus guidelines concluding that H. pylori eradication has no effects on symptoms and does not aggravate preexisting GERD. PMID:27531536

  18. The Laminin Response in Inflammatory Bowel Disease: Protection or Malignancy?

    PubMed Central

    Spenlé, Caroline; Lefebvre, Olivier; Lacroute, Joël; Méchine-Neuville, Agnès; Barreau, Frédérick; Blottière, Hervé M.; Duclos, Bernard; Arnold, Christiane; Hussenet, Thomas; Hemmerlé, Joseph; Gullberg, Donald; Kedinger, Michèle; Sorokin, Lydia; Orend, Gertraud; Simon-Assmann, Patricia

    2014-01-01

    Laminins (LM), basement membrane molecules and mediators of epithelial-stromal communication, are crucial in tissue homeostasis. Inflammatory Bowel Diseases (IBD) are multifactorial pathologies where the microenvironment and in particular LM play an important yet poorly understood role in tissue maintenance, and in cancer progression which represents an inherent risk of IBD. Here we showed first that in human IBD colonic samples and in murine colitis the LMα1 and LMα5 chains are specifically and ectopically overexpressed with a concomitant nuclear p53 accumulation. Linked to this observation, we provided a mechanism showing that p53 induces LMα1 expression at the promoter level by ChIP analysis and this was confirmed by knockdown in cell transfection experiments. To mimic the human disease, we induced colitis and colitis-associated cancer by chemical treatment (DSS) combined or not with a carcinogen (AOM) in transgenic mice overexpressing LMα1 or LMα5 specifically in the intestine. We demonstrated that high LMα1 or LMα5 expression decreased susceptibility towards experimentally DSS-induced colon inflammation as assessed by histological scoring and decrease of pro-inflammatory cytokines. Yet in a pro-oncogenic context, we showed that LM would favor tumorigenesis as revealed by enhanced tumor lesion formation in both LM transgenic mice. Altogether, our results showed that nuclear p53 and associated overexpression of LMα1 and LMα5 protect tissue from inflammation. But in a mutation setting, the same LM molecules favor progression of IBD into colitis-associated cancer. Our transgenic mice represent attractive new models to acquire knowledge about the paradoxical effect of LM that mediate either tissue reparation or cancer according to the microenvironment. In the early phases of IBD, reinforcing basement membrane stability/organization could be a promising therapeutic approach. PMID:25347196

  19. Helicobacter pylori and non-malignant upper gastrointestinal diseases.

    PubMed

    Vasapolli, Riccardo; Malfertheiner, Peter; Kandulski, Arne

    2016-09-01

    Peptic ulcer disease (PUD) has been further decreased over the last decades along with decreasing prevalence of Helicobacter pylori-associated PUD. A delayed H. pylori eradication has been associated with an increased risk of rehospitalization for complicated recurrent peptic ulcer and reemphasized the importance of eradication especially in patients with peptic ulcer bleeding (PUB). PUB associated with NSAID/aspirin intake and H. pylori revealed an additive interaction in gastric pathophysiology which favors the "test-and-treat" strategy for H. pylori in patients with specific risk factors. The H. pylori-negative and NSAID-negative "idiopathic PUD" have been increasingly observed and associated with slower healing tendency, higher risk of recurrence, and greater mortality. Helicobacter pylori-associated dyspepsia has been further investigated and finally defined by the Kyoto consensus. Helicobacter pylori eradication therapy is advised as first option in this group of patients. Only in the case of symptom persistence or recurrence after eradication therapy, dyspeptic patients should be classified as functional dyspepsia (FD). There were few new data in 2015 on the role of H. pylori infection in gastroesophageal reflux disease (GERD), and in particular Barrett's esophagus. A lower prevalence of gastric atrophy with less acid output in patients with erosive esophagitis confirmed previous findings. In patients with erosive esophagitis, no difference was observed in healing rates neither between H. pylori-positive and H. pylori-negative patients nor between patients that underwent eradication therapy compared to patients without eradication. These findings are in line with the current consensus guidelines concluding that H. pylori eradication has no effects on symptoms and does not aggravate preexisting GERD.

  20. A phase I trial to determine the safety of imatinib in combination with vatalanib in patients with advanced malignancies.

    PubMed

    Spigel, David; Jones, Suzanne; Hainsworth, John; Infante, Jeff; Greco, F Anthony; Thompson, Dana; Doss, Habib; Burris, Howard

    2011-05-01

    The role of tyrosine kinase inhibitors (TKIs) in the treatment of advanced malignancies is well established. Imatinib and vatalanib are oral TKIs with different mechanisms of action. This trial sought to establish the safety, tolerability, and maximum tolerated dose (MTD) of the two agents in combination. Secondary objectives included determination of potential pharmacologic interactions among vatalanib and imatinib and observation of antitumor activity. Patients with biopsy-proven advanced refractory solid tumors were enrolled in this single-center dose-escalation trial. Patients initially received imatinib and vatalanib once daily following a 14-day run-in period of daily oral vatalanib only, and were observed for a full 28-day treatment cycle prior to dose escalation. An amendment divided the vatalanib dose into two daily doses and gradually escalated the dose over a 2-3 week period. Patients continued combination therapy until disease progression or intolerable toxicity. Forty-five patients were enrolled between September 2004 and November 2007. As of September 2009, a total of 247 cycles of treatment had been administered (range: 1 -44+, median = 2 ). The MTD was determined to be vatalanib 1250 mg daily and imatinib 400 mg daily. Thirty-five patients (78%) were evaluable for response; 2 patients achieved PR, while 14 patients had SD ( 10 had stable disease ≥ 6 cycles). The combination of vatalanib and imatinib was well tolerated. Twice-daily vatalanib dosing improved tolerability and ease of full-dose administration. These results suggest that vatalanib-containing combinations may be active and tolerable, warranting further study. PMID:21469980

  1. Advances in conditioning regimens for older adults undergoing allogeneic stem cell transplantation to treat hematologic malignancies.

    PubMed

    William, Basem M; de Lima, Marcos

    2013-06-01

    Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematological malignancies. These diseases, however, have their peak incidence in the sixth to eighth decades of life. Historically, elderly patients have been considered unsuitable candidates for SCT because of high treatment-related mortality (TRM). Over the past 15 years, the use of reduced-intensity conditioning (RIC) regimens before SCT has allowed patients in the sixth and seventh decades of life to be routinely transplanted. Despite major differences among transplant centers in the intensity and composition of the conditioning regimen and immunosuppression, choice of graft source, postgraft immunomodulation, and supportive care, there has been a dramatic decrease in TRM, allowing safer delivery of SCT. Major obstacles to SCT in elderly patients include donor availability, graft-versus-host disease, delayed immune recovery, multiple comorbidities, and chemo refractoriness. Here we review the current results of SCT in elderly patients, focusing on the role of RIC, and using myeloid diseases as the model for discussion.

  2. Spray cryotherapy (SCT): institutional evolution of techniques and clinical practice from early experience in the treatment of malignant airway disease

    PubMed Central

    Turner, J. Francis; Parrish, Scott

    2015-01-01

    Background Spray cryotherapy (SCT) was initially developed for gastroenterology (GI) endoscopic use in the esophagus. In some institutions where a device has been utilized by GI, transition to use in the airways by pulmonologists and thoracic surgeons occurred. Significant differences exist, however, in the techniques for safely using SCT in the airways. Methods We describe the early experience at Walter Reed National Military Medical Center from 2011 to 2013 using SCT in patients with malignant airway disease and the evolution of our current techniques and clinical practice patterns for SCT use in patients. In November 2013 enrollment began in a multi-institutional prospective SCT registry in which we are still enrolling and will be reported on separately. Results Twenty-seven patients that underwent 80 procedures (2.96 procedures/patient). The average age was 63 years with a range of 20 to 87 years old. The average Eastern Cooperative Oncology Group (ECOG) status was 1.26. All malignancies were advanced stage disease. All procedures were performed in the central airways. Other modalities were used in combination with SCT in 31 (39%) of procedures. Additionally 45 of the 80 (56%) procedures were performed in proximity to a silicone, hybrid, or metal stent. Three complications occurred out of the 80 procedures. All three were transient hypoxia that limited continued SCT treatments. These patients were all discharged from the bronchoscopy recovery room to their pre-surgical state. Conclusions SCT can be safely used for treatment of malignant airway tumor (MAT) in the airways. Understanding passive venting of the nitrogen gas produced as the liquid nitrogen changes to gas is important for safe use of the device. Complications can be minimized by adopting strict protocols to maximize passive venting and to allow for adequate oxygenation in between sprays. PMID:26807288

  3. Advances in microfluidics in combating infectious diseases.

    PubMed

    Tay, Andy; Pavesi, Andrea; Yazdi, Saeed Rismani; Lim, Chwee Teck; Warkiani, Majid Ebrahimi

    2016-01-01

    One of the important pursuits in science and engineering research today is to develop low-cost and user-friendly technologies to improve the health of people. Over the past decade, research efforts in microfluidics have been made to develop methods that can facilitate low-cost diagnosis of infectious diseases, especially in resource-poor settings. Here, we provide an overview of the recent advances in microfluidic devices for point-of-care (POC) diagnostics for infectious diseases and emphasis is placed on malaria, sepsis and AIDS/HIV. Other infectious diseases such as SARS, tuberculosis, and dengue are also briefly discussed. These infectious diseases are chosen as they contribute the most to disability-adjusted life-years (DALYs) lost according to the World Health Organization (WHO). The current state of research in this area is evaluated and projection toward future applications and accompanying challenges are also discussed. PMID:26854743

  4. [The experience of disease and treatments among teenagers and young adults with hematological malignancies].

    PubMed

    Polomeni, Alice

    2011-10-01

    We conducted an exploratory study of young patients (< 25 years) in remission from hematologic malignancies to better understand their experiences of care, the impact of disease and therapeutics on their quality of life (assessed by the FACT-BMT) and on their mental state (assessed by the HADS). On the plan of research, the findings of this study confirm the relevance of the qualitative approach; on the plan of care, the need of interdisciplinary support for these patients in remission.

  5. Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease

    PubMed Central

    Zhang, Daolun; Fakhoury, May; Fahd, Mony; Duquesne, Frédérique; Storme, Thomas; Baruchel, André

    2014-01-01

    An increase in vancomycin dose has been proposed in adults with malignant hematological disease. As pediatric data are limited, our aim was to evaluate the population pharmacokinetics of vancomycin in order to define the appropriate dosing regimen in children with malignant hematological disease. Vancomycin concentrations were collected prospectively during therapeutic monitoring. Population pharmacokinetic analysis was performed using NONMEM software. Seventy children (age range, 0.3 to 17.7 years) were included. With the current recommended dosing regimen of 40 to 60 mg/kg/day, 53 children (76%) had subtherapeutic steady-state trough concentrations (Css/min of <10 mg/liter). A one-compartment model with first-order elimination was developed. Systematic covariate analysis identified that weight significantly influenced clearance (CL) and volume of distribution (V) with power functions of 0.677 for CL and 0.838 for V. Vancomycin CL also significantly increased with increases in creatinine clearance and seemed to be higher in children with malignant hematological disease than in the general pediatric population. The model was validated internally. Its predictive performance was further confirmed in an external validation by Bayesian estimation. A patient-tailored dosing regimen was developed based on the final pharmacokinetic model and showed that a higher proportion of patients reached the target Css/min than with the traditional mg/kg-basis dose (60% versus 49%) and that the risks associated with underdosing or overdosing were reduced. This is the first population pharmacokinetic study of vancomycin in children with malignant hematological disease. An optimized dosing regimen, taking into account patient weight, creatinine clearance, and susceptibility of the pathogens involved, could routinely be used to individualize vancomycin therapy in this vulnerable population. PMID:24663023

  6. Systematic review of emergent laparoscopic colorectal surgery for benign and malignant disease.

    PubMed

    Chand, Manish; Siddiqui, Muhammed R S; Gupta, Ashish; Rasheed, Shahnawaz; Tekkis, Paris; Parvaiz, Amjad; Mirnezami, Alex H; Qureshi, Tahseen

    2014-12-01

    Laparoscopic surgery has become well established in the management of both and malignant colorectal disease. The last decade has seen increasing numbers of surgeons trained to a high standard in minimally-invasive surgery. However there has not been the same enthusiasm for the use of laparoscopy in emergency colorectal surgery. There is a perception that emergent surgery is technically more difficult and may lead to worse outcomes. The present review aims to provide a comprehensive and critical appraisal of the available literature on the use of laparoscopic colorectal surgery (LCS) in the emergency setting. The literature is broadly divided by the underlying pathology; that is, inflammatory bowel disease, diverticulitis and malignant obstruction. There were no randomized trials and the majority of the studies were case-matched series or comparative studies. The overall trend was that LCS is associated with shorter hospital stay, par or fewer complications but an increased operating time.Emergency LCS can be safely undertaken for both benign and malignant disease providing there is appropriate patient selection, the surgeon is adequately experienced and there are sufficient resources to allow for a potentially more complex operation. PMID:25493008

  7. Systematic review of emergent laparoscopic colorectal surgery for benign and malignant disease

    PubMed Central

    Chand, Manish; Siddiqui, Muhammed RS; Gupta, Ashish; Rasheed, Shahnawaz; Tekkis, Paris; Parvaiz, Amjad; Mirnezami, Alex H; Qureshi, Tahseen

    2014-01-01

    Laparoscopic surgery has become well established in the management of both and malignant colorectal disease. The last decade has seen increasing numbers of surgeons trained to a high standard in minimally-invasive surgery. However there has not been the same enthusiasm for the use of laparoscopy in emergency colorectal surgery. There is a perception that emergent surgery is technically more difficult and may lead to worse outcomes. The present review aims to provide a comprehensive and critical appraisal of the available literature on the use of laparoscopic colorectal surgery (LCS) in the emergency setting. The literature is broadly divided by the underlying pathology; that is, inflammatory bowel disease, diverticulitis and malignant obstruction. There were no randomized trials and the majority of the studies were case-matched series or comparative studies. The overall trend was that LCS is associated with shorter hospital stay, par or fewer complications but an increased operating time.Emergency LCS can be safely undertaken for both benign and malignant disease providing there is appropriate patient selection, the surgeon is adequately experienced and there are sufficient resources to allow for a potentially more complex operation. PMID:25493008

  8. Coexistence of malignant phyllodes tumor and her2-positive locally advanced breast cancer in distinct breasts: A case report

    PubMed Central

    Sato, Tomoi; Muto, Ichiro; Sakai, Takeshi

    2016-01-01

    Introduction Phyllodes tumor of the breast is a rare biphasic neoplasm, accounting for less than 1% of all breast tumors. Coexistence of phyllodes tumor and breast cancer in distinct breasts is extremely rare. Case presentation A 47-year-old Japanese woman presented with bilateral breast lumps. A HER2-positive, unresectable invasive carcinoma in the right breast and fibroadenoma in the left were diagnosed via core needle biopsy. During chemotherapy with anti-HER2 therapy, the breast cancer shrank quickly, while the left breast lump suddenly enlarged. Under a diagnosis of malignant neoplasm of the breast, left mastectomy was performed. Malignant phyllodes tumor was diagnosed by postoperative histological examination and recurred in multiple areas as early as 2 months after surgery. Discussion Only 10 cases of coexisting phyllodes tumor and breast cancer in distinct breasts have been reported in the English literature. Phyllodes tumor associated with breast cancer in distinct breasts tends to be malignant. This is the first case of phyllodes tumor rapidly enlarging during anti-HER2 chemotherapy for locally advanced HER2-positive breast cancer. Conclusion Even during effective treatment of advanced or recurrent breast cancer, attention should also be paid to the contralateral breast for the possible association of a second malignancy such as phyllodes tumor. PMID:26773878

  9. [Diagnostic pitfalls in benign and malignant salivary gland diseases. Their significance for prognosis and therapy].

    PubMed

    Seifert, G

    1998-03-01

    Diagnostic pitfalls exist when benign salivary gland diseases are mistakenly classified as malignant, with consequences for treatment and prognosis. Examples are necrotizing sialometaplasia, metaplastic Warthin tumour and sclerosing polycystic sialadenopathy. The proper diagnosis is of eminent importance to distinguish cases of primary tumours that have developed in salivary glands or their lymph nodes from cases of extraglandular tumours with metastases in these glands or their nodes. In these cases clinical data and additional immunocytochemical methods are necessary to clarify the exact diagnosis, especially when the primary salivary gland tumours have a structure largely identical to the metastases (e.g. squamous cell carcinoma). Nasopharyngeal or cervical chordomas can be mistaken for pleomorphic adenoma or mucinous adenocarcinoma. The initial stage of malignant MALT lymphomas in association with Sjögren's syndrome demands identification of clonal rearrangement for therapeutic implication. The diagnostic criteria for proper classification are analysed in detail.

  10. Research advances in esophageal diseases: bench to bedside

    PubMed Central

    di Pietro, Massimiliano

    2013-01-01

    Over the last year, significant steps have been made toward understanding the pathogenesis of esophageal diseases and translating this knowledge to clinical practice. Gastroesophageal reflux disease (GERD) is the most common outpatient diagnosis in gastroenterology and has a high prevalence in the general population. As many as 40% of patients with GERD have incomplete response to medical therapy, and the pathophysiological mechanisms underlying lack of response are now better understood. Novel medical and minimally invasive interventions are available to optimize management of GERD. Esophageal cancer, regardless of the histological subtype, has among the worst survival statistics among all malignancies. Taking advantage of technological advances in genome sequencing, the mutational spectra in esophageal cancer are now emerging, offering novel avenues for targeted therapies. Early diagnosis is another strand for improving survival. While genome-wide association studies are providing insights into genetic susceptibility, novel approaches to early detection of cancer are being devised through the use of biomarkers applied to esophageal samples and as part of imaging technologies. Dysmotility and eosinophilic esophagitis are the differential diagnoses in patients with dysphagia. New pathophysiological classifications have improved the management of motility disorders. Meanwhile, exciting progress has been made in the endoscopic management of these conditions. Eosinophilic esophagitis is still a relatively new entity, and the pathogenesis remains poorly understood. However, it is now clear that an allergic reaction to food plays an important role, and dietary interventions as well as biologic agents to block the inflammatory cascade are novel, promising fields of clinical research. PMID:24167725

  11. Vascular Normalization as a Therapeutic Strategy for Malignant and Nonmalignant Disease

    PubMed Central

    Goel, Shom; Wong, Andus Hon-Kit; Jain, Rakesh K.

    2012-01-01

    Pathological angiogenesis—driven by an imbalance of pro- and antiangiogenic signaling—is a hallmark of many diseases, both malignant and benign. Unlike in the healthy adult in which angiogenesis is tightly regulated, such diseases are characterized by uncontrolled new vessel formation, resulting in a microvascular network characterized by vessel immaturity, with profound structural and functional abnormalities. The consequence of these abnormalities is further modification of the microenvironment, often serving to fuel disease progression and attenuate response to conventional therapies. In this article, we present the “vascular normalization” hypothesis, which states that antiangiogenic therapy, by restoring the balance between pro- and antiangiogenic signaling, can induce a more structurally and functionally normal vasculature in a variety of diseases. We present the preclinical and clinical evidence supporting this concept and discuss how it has contributed to successful treatment of both solid tumors and several benign conditions. PMID:22393532

  12. Endoscopic versus Percutaneous Biliary Drainage in Palliation of Advanced Malignant Hilar Obstruction: A Meta-Analysis and Systematic Review

    PubMed Central

    Dharmapuri, Sirish; Duvvuri, Abhiram; Dharmapuri, Sowmya; Boddireddy, Raghuveer; Moole, Vishnu; Yedama, Prathyusha; Bondalapati, Naveen; Uppu, Achuta

    2016-01-01

    Background. Palliation in advanced unresectable hilar malignancies can be achieved by endoscopic (EBD) or percutaneous transhepatic biliary drainage (PTBD). It is unclear if one approach is superior to the other in this group of patients. Aims. Compare clinical outcomes of EBD versus PTBD. Methods. (i) Study Selection Criterion. Studies using PTBD and EBD for palliation of advanced unresectable hilar malignancies. (ii) Data Collection and Extraction. Articles were searched in Medline, PubMed, and Ovid journals. (iii) Statistical Method. Fixed and random effects models were used to calculate the pooled proportions. Results. Initial search identified 786 reference articles, in which 62 articles were selected and reviewed. Data was extracted from nine studies (N = 546) that met the inclusion criterion. The pooled odds ratio for successful biliary drainage in PTBD versus EBD was 2.53 (95% CI = 1.57 to 4.08). Odds ratio for overall adverse effects in PTBD versus EBD groups was 0.81 (95% CI = 0.52 to 1.26). Odds ratio for 30-day mortality rate in PTBD group versus EBD group was 0.84 (95% CI = 0.37 to 1.91). Conclusions. In patients with advanced unresectable hilar malignancies, palliation with PTBD seems to be superior to EBD. PTBD is comparable to EBD in regard to overall adverse effects and 30-day mortality.

  13. Endoscopic versus Percutaneous Biliary Drainage in Palliation of Advanced Malignant Hilar Obstruction: A Meta-Analysis and Systematic Review.

    PubMed

    Moole, Harsha; Dharmapuri, Sirish; Duvvuri, Abhiram; Dharmapuri, Sowmya; Boddireddy, Raghuveer; Moole, Vishnu; Yedama, Prathyusha; Bondalapati, Naveen; Uppu, Achuta; Yerasi, Charan

    2016-01-01

    Background. Palliation in advanced unresectable hilar malignancies can be achieved by endoscopic (EBD) or percutaneous transhepatic biliary drainage (PTBD). It is unclear if one approach is superior to the other in this group of patients. Aims. Compare clinical outcomes of EBD versus PTBD. Methods. (i) Study Selection Criterion. Studies using PTBD and EBD for palliation of advanced unresectable hilar malignancies. (ii) Data Collection and Extraction. Articles were searched in Medline, PubMed, and Ovid journals. (iii) Statistical Method. Fixed and random effects models were used to calculate the pooled proportions. Results. Initial search identified 786 reference articles, in which 62 articles were selected and reviewed. Data was extracted from nine studies (N = 546) that met the inclusion criterion. The pooled odds ratio for successful biliary drainage in PTBD versus EBD was 2.53 (95% CI = 1.57 to 4.08). Odds ratio for overall adverse effects in PTBD versus EBD groups was 0.81 (95% CI = 0.52 to 1.26). Odds ratio for 30-day mortality rate in PTBD group versus EBD group was 0.84 (95% CI = 0.37 to 1.91). Conclusions. In patients with advanced unresectable hilar malignancies, palliation with PTBD seems to be superior to EBD. PTBD is comparable to EBD in regard to overall adverse effects and 30-day mortality. PMID:27648439

  14. Endoscopic versus Percutaneous Biliary Drainage in Palliation of Advanced Malignant Hilar Obstruction: A Meta-Analysis and Systematic Review

    PubMed Central

    Dharmapuri, Sirish; Duvvuri, Abhiram; Dharmapuri, Sowmya; Boddireddy, Raghuveer; Moole, Vishnu; Yedama, Prathyusha; Bondalapati, Naveen; Uppu, Achuta

    2016-01-01

    Background. Palliation in advanced unresectable hilar malignancies can be achieved by endoscopic (EBD) or percutaneous transhepatic biliary drainage (PTBD). It is unclear if one approach is superior to the other in this group of patients. Aims. Compare clinical outcomes of EBD versus PTBD. Methods. (i) Study Selection Criterion. Studies using PTBD and EBD for palliation of advanced unresectable hilar malignancies. (ii) Data Collection and Extraction. Articles were searched in Medline, PubMed, and Ovid journals. (iii) Statistical Method. Fixed and random effects models were used to calculate the pooled proportions. Results. Initial search identified 786 reference articles, in which 62 articles were selected and reviewed. Data was extracted from nine studies (N = 546) that met the inclusion criterion. The pooled odds ratio for successful biliary drainage in PTBD versus EBD was 2.53 (95% CI = 1.57 to 4.08). Odds ratio for overall adverse effects in PTBD versus EBD groups was 0.81 (95% CI = 0.52 to 1.26). Odds ratio for 30-day mortality rate in PTBD group versus EBD group was 0.84 (95% CI = 0.37 to 1.91). Conclusions. In patients with advanced unresectable hilar malignancies, palliation with PTBD seems to be superior to EBD. PTBD is comparable to EBD in regard to overall adverse effects and 30-day mortality. PMID:27648439

  15. Management of thrombocytopenia in advanced liver disease

    PubMed Central

    Gangireddy, VGR; Kanneganti, PC; Sridhar, S; Talla, S; Coleman, T

    2014-01-01

    Thrombocytopenia (defined as a platelet count <150×109/L) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×109/L to 75×109/L) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease. PMID:25222481

  16. Scientifically advanced solutions for chestnut ink disease.

    PubMed

    Choupina, Altino Branco; Estevinho, Letícia; Martins, Ivone M

    2014-05-01

    On the north regions of Portugal and Spain, the Castanea sativa Mill. culture is extremely important. The biggest productivity and yield break occurs due to the ink disease, the causal agent being the oomycete Phytophthora cinnamomi. This oomycete is also responsible for the decline of many other plant species in Europe and worldwide. P. cinnamomi and Phytophthora cambivora are considered, by the generality of the authors, as the C. sativa ink disease causal agents. Most Phytophthora species secrete large amounts of elicitins, a group of unique highly conserved proteins that are able to induce hypersensitive response (HR) and enhances plant defense responses in a systemic acquired resistance (SAR) manner against infection by different pathogens. Some other proteins involved in mechanisms of infection by P. cinnamomi were identified by our group: endo-1,3-beta-glucanase (complete cds); exo-glucanase (partial cds) responsible by adhesion, penetration, and colonization of host tissues; glucanase inhibitor protein (GIP) (complete cds) responsible by the suppression of host defense responses; necrosis-inducing Phytophthora protein 1 (NPP1) (partial cds); and transglutaminase (partial cds) which inducts defense responses and disease-like symptoms. In this mini-review, we present some scientifically advanced solutions that can contribute to the resolution of ink disease.

  17. The effect of increased experience on complications in robotic hysterectomy for malignant and benign gynecological disease.

    PubMed

    Lönnerfors, Celine; Reynisson, Petur; Geppert, Barbara; Persson, Jan

    2015-12-01

    The study objective was to assess the effect of increased experience on complications in robotic hysterectomy for malignant and benign gynecological disease. This is a retrospective cohort study. It is a Canadian Task Force classification II-2 study conducted at the University Hospital, Sweden. The patients were 949 women planned for robotic hysterectomy for malignant (75 %) and benign (25 %) gynecological disease between October 2005 and December 2013. They were continuously evaluated for the rate of intraoperative and postoperative complications up to 1-year post-surgery, the latter according to Clavien-Dindo classification following the introduction of robotic surgery with special awareness of complications possibly related to robot-specific risk factors, the description of refinement of practice and assessment of the effect of these measures. The rate of intraoperative complications, the overall rate of complications and the rate of ≥grade 3 complications decreased from the first to the last time period (4.8 vs 2.6 %, p = 0.037, 34 vs 19 %, p = 0.003 and 13.5 vs 3.2 %, p = 0.0003, respectively). The rate of intraoperative complications and the rate of postoperative complications possibly related to robot-specific risk factors was reduced from the first to the last time period (3.8 vs 0.6 %, p = 0.028 and 7.7 vs 1.5 %, p = 0.003, respectively). In patients undergoing robotic hysterectomy for malignant and benign gynecological disease intraoperative and postoperative complications and complications possibly related to the robotic approach diminish with training, experience and refinement of practice. PMID:26530844

  18. [Dermatological diseases of the external male genitalia : Part 2: Infectious and malignant dermatological].

    PubMed

    Köhn, F M; Schultheiss, D; Krämer-Schultheiss, K

    2016-07-01

    The urological and andrological examination of male patients should include inspection of the genital skin in order to detect malignant neoplasms, such as erythroplasia of Queyrat and infectious diseases, such as genital warts (condylomata acuminata). Independent of the incidental finding of relevant dermatological alterations in the genital area, sexually transmitted diseases such as syphilis must again be considered more often as the incidence has greatly increased in Germany during the last few years. In addition, urologists should be able to adequately advise patients on all aspects of diseases caused by human papillomavirus. As patients are often alarmed by genital skin lesions and worried that the sex life can be impaired, the initiation of adequate therapy is of great importance. PMID:27364818

  19. Clinical utility of (18)F-fluoride PET/CT in benign and malignant bone diseases.

    PubMed

    Li, Yuxin; Schiepers, Christiaan; Lake, Ralph; Dadparvar, Simin; Berenji, Gholam R

    2012-01-01

    (18)F labeled sodium fluoride is a positron-emitting, bone seeking agent with more favorable skeletal kinetics than conventional phosphate and diphosphonate compounds. With the expanding clinical usage of PET/CT, there is renewed interest in using (18)F-fluoride PET/CT for imaging bone diseases. Growing evidence indicates that (18)F fluoride PET/CT offers increased sensitivity, specificity, and diagnostic accuracy in evaluating metastatic bone disease compared to (99m)Tc based bone scintigraphy. National Oncologic PET Registry (NOPR) has expanded coverage for (18)F sodium fluoride PET scans since February 2011 for the evaluation of osseous metastatic disease. In this article, we reviewed the pharmacological characteristics of sodium fluoride, as well as the clinical utility of PET/CT using (18)F-fluoride in both benign and malignant bone disorders.

  20. The effect of obesity on outcome of unrelated cord blood transplant in children with malignant diseases.

    PubMed

    Pine, M; Wang, L; Harrell, F E; Calder, C; Manes, B; Evans, M; Domm, J; Frangoul, H

    2011-10-01

    Obesity has become a pandemic, affecting both children and adults. We sought to determine the effect of obesity among 200 children who were prospectively enrolled on a multicenter cord blood transplant (CBT) trial. All patients received myeloablative preparative regimens. Children were classified into groups according to body mass index percentile. Normal weight was defined as body mass index between the 5th and 85th percentile (n=117), overweight between the 85th and 95th percentile (n=35) and obesity above 95th percentile (n=39) for age and gender. A total of 55 patients (27%) had AML, 113 patients (57%) had ALL and 32 patients (16%) had other malignant diseases. There was no evidence for a difference in all major characteristics among the groups. Time to neutrophil and platelet engraftment, TRM, risk of acute GVHD, disease-free survival and OS were not significantly different in overweight or obese patients compared with normal weight patients. There was a trend towards increased risk of chronic GVHD in obese patients (P=0.05) compared with normal weight patients. In conclusion, there is insufficient evidence from this sample that obesity has an effect on multiple outcomes after unrelated CBT in children with malignant diseases.

  1. Risk of ovarian failure and fertility preserving methods in girls and adolescents with a malignant disease.

    PubMed

    Schmidt, K T; Larsen, E C; Andersen, C Y; Andersen, A N

    2010-01-01

    Girls and young women suffering from a malignant disease that requires treatment with chemo- and/or radiotherapy are at risk of losing fertility. The most significant risk factors are age and type of treatment given. Preserving fertility is of high priority to both the young patient and her parents. This article reviews the effect of chemo- and radiotherapy on gonadal function, and thus fertility, and offers different fertility preserving methods based on the literature. Cryopreservation of ovarian tissue is a possible way of preserving fertility in this group of patients in the future. PMID:19874293

  2. Female Sexual Dysfunction in Women with Non-Malignant Cervical Diseases: A Study from an Urban Chinese Sample

    PubMed Central

    Zhang, Aixia; Lei, Yu; Yang, Bin; Li, Ping; Pan, Lianjun

    2015-01-01

    Non-malignant cervical diseases are common causes of disease among women worldwide. Although many studies have focused on sexual function in women with cervical cancer, little is known about the prevalence of female sexual dysfunction and its risk factors in women with non-malignant cervical diseases. The present study aims to assess sexual function in Chinese women with non-malignant cervical diseases and to identify potential risk factors for these diseases. A cross-sectional hospital-based survey was conducted in Nanjing, China. The Chinese version of the Female Sexual Function Index (CVFSFI) was used to evaluate sexual function. Three hundred three women who had been diagnosed with at least one non-malignant cervical disease and 293 healthy women were recruited from Nanjing Maternity and Child Health Hospital of Nanjing Medical University. We found that women with non-malignant cervical diseases had a significantly higher prevalence of female sexual dysfunction (FSD) (51.8% vs. 34.8%), low desire (43.2% vs. 26.3%), arousal disorder (41.6% vs. 28.3%), and lubrication disorder (51.2% vs. 36.9%) compared with the control group. Cervicitis and cervical intraepithelial neoplasia (CIN) were found to be independent risk factors for FSD. Our study indicates that women with cervicitis and CIN are at a high risk for FSD and deserve focused initial and follow-up management. PMID:26473480

  3. Recent Advances in Autoimmune Thyroid Diseases

    PubMed Central

    Yoo, Won Sang

    2016-01-01

    Autoimmune thyroid disease (AITD) includes hyperthyroid Graves disease, hypothyroid autoimmune thyroiditis, and subtle subclinical thyroid dysfunctions. AITD is caused by interactions between genetic and environmental predisposing factors and results in autoimmune deterioration. Data on polymorphisms in the AITD susceptibility genes, related environmental factors, and dysregulation of autoimmune processes have accumulated over time. Over the last decade, there has been progress in the clinical field of AITD with respect to the available diagnostic and therapeutic methods as well as clinical consensus. The updated clinical guidelines allow practitioners to identify the most reasonable and current approaches for proper management. In this review, we focus on recent advances in understanding the genetic and environmental pathogenic mechanisms underlying AITD and introduce the updated set of clinical guidelines for AITD management. We also discuss other aspects of the disease such as management of subclinical thyroid dysfunction, use of levothyroxine plus levotriiodothyronine in the treatment of autoimmune hypothyroidism, risk assessment of long-standing antithyroid drug therapy in recurrent Graves' hyperthyroidism, and future research needs. PMID:27586448

  4. The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease

    PubMed Central

    Hieken, Tina J.; Chen, Jun; Hoskin, Tanya L.; Walther-Antonio, Marina; Johnson, Stephen; Ramaker, Sheri; Xiao, Jian; Radisky, Derek C.; Knutson, Keith L.; Kalari, Krishna R.; Yao, Janet Z.; Baddour, Larry M.; Chia, Nicholas; Degnim, Amy C.

    2016-01-01

    Globally breast cancer is the leading cause of cancer death among women. The breast consists of epithelium, stroma and a mucosal immune system that make up a complex microenvironment. Growing awareness of the role of microbes in the microenvironment recently has led to a series of findings important for human health. The microbiome has been implicated in cancer development and progression at a variety of body sites including stomach, colon, liver, lung, and skin. In this study, we assessed breast tissue microbial signatures in intraoperatively obtained samples using 16S rDNA hypervariable tag sequencing. Our results indicate a distinct breast tissue microbiome that is different from the microbiota of breast skin tissue, breast skin swabs, and buccal swabs. Furthermore, we identify distinct microbial communities in breast tissues from women with cancer as compared to women with benign breast disease. Malignancy correlated with enrichment in taxa of lower abundance including the genera Fusobacterium, Atopobium, Gluconacetobacter, Hydrogenophaga and Lactobacillus. This work confirms the existence of a distinct breast microbiome and differences between the breast tissue microbiome in benign and malignant disease. These data provide a foundation for future investigation on the role of the breast microbiome in breast carcinogenesis and breast cancer prevention. PMID:27485780

  5. Newcastle disease virus, rituximab, and doxorubicin combination as anti-hematological malignancy therapy.

    PubMed

    Al-Shammari, Ahmed Majeed; Rameez, Huda; Al-Taee, Maha F

    2016-01-01

    Hematological malignancies are important diseases that need more powerful therapeutics. Even with current targeting therapies, such as rituximab and other chemotherapeutic agents, there is a need to develop new treatment strategies. Combination therapy seems the best option to target the tumor cells by different mechanisms. Virotherapy is a very promising treatment modality, as it is selective, safe, and causes cancer destruction. The Iraqi strain of Newcastle disease virus (NDV) has proved to be effective both in vitro and in vivo. In the current work, we tested its ability on anti-hematological tumors and enhanced current treatments with combination therapy, and studied this combination using Chou-Talalay analysis. p53 concentration was measured to evaluate the mechanism of this proposed synergism. The results showed that NDV was synergistic with doxorubicin in low doses on plasmacytoma cells, with no involvement of p53 pathways, but involved p53 when the combination was used on non-Hodgkin lymphoma cells. NDV in combination with rituximab showed enhanced cytotoxicity that was p53-independent. In conclusion, this work proposes a novel combination modality for treatment of some hematological malignancies. PMID:27579294

  6. The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease.

    PubMed

    Hieken, Tina J; Chen, Jun; Hoskin, Tanya L; Walther-Antonio, Marina; Johnson, Stephen; Ramaker, Sheri; Xiao, Jian; Radisky, Derek C; Knutson, Keith L; Kalari, Krishna R; Yao, Janet Z; Baddour, Larry M; Chia, Nicholas; Degnim, Amy C

    2016-01-01

    Globally breast cancer is the leading cause of cancer death among women. The breast consists of epithelium, stroma and a mucosal immune system that make up a complex microenvironment. Growing awareness of the role of microbes in the microenvironment recently has led to a series of findings important for human health. The microbiome has been implicated in cancer development and progression at a variety of body sites including stomach, colon, liver, lung, and skin. In this study, we assessed breast tissue microbial signatures in intraoperatively obtained samples using 16S rDNA hypervariable tag sequencing. Our results indicate a distinct breast tissue microbiome that is different from the microbiota of breast skin tissue, breast skin swabs, and buccal swabs. Furthermore, we identify distinct microbial communities in breast tissues from women with cancer as compared to women with benign breast disease. Malignancy correlated with enrichment in taxa of lower abundance including the genera Fusobacterium, Atopobium, Gluconacetobacter, Hydrogenophaga and Lactobacillus. This work confirms the existence of a distinct breast microbiome and differences between the breast tissue microbiome in benign and malignant disease. These data provide a foundation for future investigation on the role of the breast microbiome in breast carcinogenesis and breast cancer prevention. PMID:27485780

  7. [Neutrophil CD64 Expression as A Biomarker in the Early Diagnosis of Sepsis in Malignant Hematologic Disease--Review].

    PubMed

    Shang, Yu-Xi; Wang, Li-Ru

    2016-02-01

    Malignant hematologic disease with sepsis has been characterized by high mortality and difficulty in diagnosis at early stage. A good biomarker may help to improve the accuracy of diagnosis and to reduce the mortality rate. In the early diagnosis of sepsis, neutrophil CD64 expression is a better candidate for biomarker rather than C-reactive proteins. Moreover, neutrophil CD64 expression is also helpful for assessing the severity of infection and prognosis of disease. Unfortunately, there are few studies of neutrophil CD64 expression on the early diagnosis of malignant hematologic diseases. This review focuses on the advantages, limitations, feasibilities and progresses of neutrophil CD64 expression in the early diagnosis of infection in malignant hematologic diseases in this paper.

  8. Limited health literacy in advanced kidney disease.

    PubMed

    Taylor, Dominic M; Bradley, John A; Bradley, Clare; Draper, Heather; Johnson, Rachel; Metcalfe, Wendy; Oniscu, Gabriel; Robb, Matthew; Tomson, Charles; Watson, Chris; Ravanan, Rommel; Roderick, Paul

    2016-09-01

    Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy. PMID:27521115

  9. Limited health literacy in advanced kidney disease.

    PubMed

    Taylor, Dominic M; Bradley, John A; Bradley, Clare; Draper, Heather; Johnson, Rachel; Metcalfe, Wendy; Oniscu, Gabriel; Robb, Matthew; Tomson, Charles; Watson, Chris; Ravanan, Rommel; Roderick, Paul

    2016-09-01

    Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy.

  10. A case-control study of malignant and non-malignant respiratory disease among employees of a fiberglass manufacturing facility. II. Exposure assessment.

    PubMed Central

    Chiazze, L; Watkins, D K; Fryar, C; Kozono, J

    1993-01-01

    A case-control study of malignant and non-malignant respiratory disease among employees of the Owens-Corning Fiberglas Corporation's Newark, Ohio plant was undertaken. The aim was to determine the extent to which exposures to substances in the Newark plant environment, to non-workplace factors, or to a combination may play a part in the risk of mortality from respiratory disease among workers in this plant. A historical environmental reconstruction of the plant was undertaken to characterise the exposure profile for workers in this plant from its beginnings in 1934 to the end of 1987. The exposure profile provided estimates of cumulative exposure to respirable fibres, fine fibres, asbestos, talc, formaldehyde, silica, and asphalt fumes. Employment histories from Owens-Corning Fiberglas provided information on employment characteristics (duration of employment, year of hire, age at first hire) and an interview survey obtained information on demographic characteristics (birthdate, race, education, marital state, parent's ethnic background, and place of birth), lifetime residence, occupational and smoking histories, hobbies, and personal and family medical history. Matched, unadjusted odds ratios (ORs) were used to assess the association between lung cancer or non-malignant respiratory disease and the cumulative exposure history, demographic characteristics, and employment variables. Only the smoking variables and employment characteristics (year of hire and age at first hire) were statistically significant for lung cancer. For non-malignant respiratory disease, only the smoking variables were statistically significant in the univariate analysis. Of the variables entered into a conditional logistic regression model for lung cancer, only smoking (smoked for six months or more v never smoked: OR = 26.17, 95% confidence interval (95% CI) 3.316-206.5) and age at first hire (35 and over v less than 35: OR = 0.244, 95% CI 0.083-0.717) were statistically significant. There

  11. Esophageal stenting for benign and malignant disease: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

    PubMed

    Spaander, Manon C W; Baron, Todd H; Siersema, Peter D; Fuccio, Lorenzo; Schumacher, Brigitte; Escorsell, Àngels; Garcia-Pagán, Juan-Carlos; Dumonceau, Jean-Marc; Conio, Massimo; de Ceglie, Antonella; Skowronek, Janusz; Nordsmark, Marianne; Seufferlein, Thomas; Van Gossum, André; Hassan, Cesare; Repici, Alessandro; Bruno, Marco J

    2016-10-01

    This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE), endorsed by the European Society for Radiotherapy and Oncology (ESTRO), the European Society of Digestive Endoscopy (ESDO), and the European Society for Clinical Nutrition and Metabolism (ESPEN). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations for malignant disease 1 ESGE recommends placement of partially or fully covered self-expandable metal stents (SEMSs) for palliative treatment of malignant dysphagia over laser therapy, photodynamic therapy, and esophageal bypass (strong recommendation, high quality evidence). 2 For patients with longer life expectancy, ESGE recommends brachytherapy as a valid alternative or in addition to stenting in esophageal cancer patients with malignant dysphagia. Brachytherapy may provide a survival advantage and possibly a better quality of life compared to SEMS placement alone. (Strong recommendation, high quality evidence.) 3 ESGE recommends esophageal SEMS placement as the preferred treatment for sealing malignant tracheoesophageal or bronchoesophageal fistula (strong recommendation, low quality evidence). 4 ESGE does not recommend the use of concurrent external radiotherapy and esophageal stent treatment. SEMS placement is also not recommended as a bridge to surgery or prior to preoperative chemoradiotherapy. It is associated with a high incidence of adverse events and alternative satisfactory options such as placement of a feeding tube are available. (Strong recommendation, low quality evidence.) Main recommendations for benign disease 1 ESGE recommends against the use of self-expandable stents (SEMSs) as first-line therapy for the management of benign esophageal strictures because of the potential for adverse events, the availability of alternative therapies, and costs (strong

  12. A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

    ClinicalTrials.gov

    2016-09-19

    Advanced Solid Tumors With Alterations of FGFR1, 2 and/or 3;; Squamous Lung Cancer With FGFR1 Amplification;; Bladder Cancer With FGFR3 Mutation or Fusion; Advanced Solid Tumors With FGFR1 Amplication,; Advanced Solid Tumors With FGFR2 Amplication,; Advanced Solid Tumors With FGFR3 Mutation

  13. Non-Malignant Thyroid Diseases Following a Wide Range of Radiation Exposures

    PubMed Central

    Ron, Elaine; Brenner, Alina

    2013-01-01

    Background The thyroid gland is one of the most radiosensitive human organs. While it is well known that radiation exposure increases the risk of thyroid cancer, less is known about its effects in relation to non-malignant thyroid diseases. Objectives The aim of this review is to evaluate the effects of high and low dose radiation on benign structural and functional diseases of the thyroid. Methods We examined the results of major studies from cancer patients treated with high-dose radiotherapy or thyrotoxicosis patients treated with high doses of iodine-131, patients treated with moderate to high dose radiotherapy for benign diseases, persons exposed to low doses from environmental radiation and survivors of the atomic bombings who were exposed to a range of doses. We evaluated radiation effects on structural (tumors, nodules), functional (hyper- and hypothyroidism), and autoimmune thyroid diseases. Results Following a wide range of doses of ionizing radiation, an increased risk of thyroid adenomas and nodules was observed in a variety of populations and settings. The dose response appeared to be linear at low to moderate doses, but in one study there was some suggestion of a reduction in risk above 5 Gy. The elevated risk for benign tumors continues for decades following exposure. Considerably less consistent findings are available regarding functional thyroid diseases including autoimmune diseases. In general, associations for these outcomes were fairly weak and significant radiation effects were most often observed following high doses, particularly for hypothyroidism. Conclusions A significant radiation dose-response relation was demonstrated for benign nodules and follicular adenomas. The effects of radiation on functional thyroid diseases are less clear, partly due to the greater difficulties studying these diseases. PMID:21128812

  14. Malignant lymphoma in patients with systemic rheumatic disease (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis): a clinicopathologic study of 24 Japanese cases.

    PubMed

    Kojima, Masaru; Itoh, Hideaki; Shimizu, Kazuhiko; Saruki, Nobuhiro; Murayama, Kayoko; Higuchi, Keiko; Tamaki, Yoshio; Matsumoto, Morio; Hirabayashi, Kaoru; Igarishi, Seiji; Masawa, Nobuhide; Nakamura, Shigeo

    2006-01-01

    We conducted clinicopathologic and immunohistochemical analyses of the prevalence of Epstein-Barr virus (EBV) among 24 patients with malignant lymphoma complicating systemic rheumatic diseases. (SRD) These 24 patients included 17 with rheumatoid arthritis (RA), 3 with systemic lupus erythematosus (SLE), 2 with systemic sclerosis (SS), and 2 with dermatomyositis (DM). There were 2 men and 22 women ranging in age from 30 to 86 years (mean: 64 years). The interval between the onset of rheumatic disease and that of malignant lymphomas ranged from 3 months to 35 years (mean: 142 months). The use of immunosuppressive drugs before the onset of malignant lymphoma was recorded in 15 patients. Among them, 5 patients received methotrexate (MTX) therapy. Malignant lymphomas were found at extranodal sites in 9 patients, and the disease was in the advanced stage in 17 patients. Histologic and immunohistochemical studies demonstrated that 18 cases (75%) were B-cell lymphoma (RA=12, SLE=2, SS=2, DM=2), 3 (12.5%) were peripheral T-cell lymphoma (RA=3), and 3 (12.5%) were classical Hodgkin lymphoma (RA=2, SLE=1). As in previous reports, there was an increased frequency of diffuse large B-cell lymphoma (50%) in the present series. Moreover, a majority of the diffuse large B-cell lymphomas exhibited activated B-cell phenotype. EBV-encoded small RNAs (Epstein-Barr early region [EBER]-) and/or LMP-1+tumor cells were identified in only 3 cases of classical Hodgkin lymphomas. Our findings suggested EBV-associated lymphoma comprised only a small fraction of all non-Hodgkin's lymphomas in the general SRD patient population.

  15. Clinical application of shear wave elastography (SWE) in the diagnosis of benign and malignant breast diseases.

    PubMed

    Chang, Jung Min; Moon, Woo Kyung; Cho, Nariya; Yi, Ann; Koo, Hye Ryoung; Han, Wonsik; Noh, Dong-Young; Moon, Hyeong-Gon; Kim, Seung Ja

    2011-08-01

    Shear wave elastography (SWE) is an emerging technique which can obtain quantitative elasticity values in breast disease. We therefore evaluated the diagnostic performance of SWE for the differentiation of breast masses compared with conventional ultrasound (US). Conventional US and SWE were performed by three experienced radiologists for 158 consecutive women who had been scheduled for US-guided core biopsy or surgical excision in 182 breast masses (89 malignancies and 93 benign; mean size, 1.76 cm). For each lesion, quantitative elasticity was measured in terms of the Young's modulus (in kilopascals, kPa) with SWE, and BI-RADS final categories were assessed with conventional US. The mean elasticity values were significantly higher in malignant masses (153.3 kPa ± 58.1) than in benign masses (46.1 kPa ± 42.9), (P < 0.0001). The average mean elasticity values of invasive ductal (157.5 ± 57.07) or invasive lobular (169.5 ± 61.06) carcinomas were higher than those of ductal carcinoma in situ (117.8 kPa ± 54.72). The average mean value was 49.58 ± 43.51 for fibroadenoma, 35.3 ± 31.2 for fibrocystic changes, 69.5 ± 63.2 for intraductal papilloma, and 149.5 ± 132.4 for adenosis or stromal fibrosis. The optimal cut-off value, yielding the maximal sum of sensitivity and specificity, was 80.17 kPa, and the sensitivity and specificity of SWE were 88.8% (79 of 89) and 84.9% (79 of 93). The area under the ROC curve (Az value) was 0.898 for conventional US, 0.932 for SWE, and 0.982 for combined data. In conclusion, there were significant differences in the elasticity values of benign and malignant masses as well as invasive and intraductal cancers with SWE. Our results suggest that SWE has the potential to aid in the differentiation of benign and malignant breast lesions.

  16. Risk of individual malignant neoplasms in patients with sickle cell disease: English national record linkage study

    PubMed Central

    Seminog, Olena O; Ogunlaja, Oyindamola I; Yeates, David

    2016-01-01

    Objective Case reports suggest that there may be an increased risk of some cancers associated with sickle cell disease. However, population-based studies are scarce and there is no comprehensive enumeration of the risks across the whole range of site-specific cancers. Our aim was to provide this. Design We used an English national dataset of linked statistical records of hospital admissions and deaths from 1999 to 2011 to undertake a retrospective cohort study. Setting England. Participants Records of all hospital admissions in England with SCD or with conditions included in the control cohort. Main outcome measures Rate ratios were calculated comparing rates of cancer in a sickle cell disease cohort and a control cohort, confining the analyses to people whose ethnicity was recorded as Black. Results Comparing the sickle cell disease cohort with the cohort without sickle cell disease, the rate ratio for all cancers combined was 2.1 (95% confidence interval 1.7–2.5). There were significantly high rate ratios for haematological malignancies, including Hodgkin’s lymphoma (rate ratio 3.7, 1.5–8.4), non-Hodgkin’s lymphoma (2.6, 1.3–4.8), multiple myeloma (5.5, 2.8–10.1), lymphoid leukaemia (3.3, 1.3–8.0) and myeloid leukaemia (10.0, 4.6–21.5). Four solid tumours showed elevated rate ratios: colon cancer (2.8, 1.2–5.5), non-melanoma skin cancer (4.4, 1.3–12.2), kidney cancer (5.4, 2.3–11.5) and thyroid cancer (5.1, 1.3–15.4). Conclusions The risk of some malignancies may be raised in patients with sickle cell disease. However, this study was based on administrative data without the scope to validate these against patients’ full clinical records. Our findings need confirmation or refutation. If confirmed, work to elucidate, at the genetic and molecular level, why people with sickle cell disease have elevated risks of individual cancers might make contributions to the fundamental understanding of carcinogenesis. PMID:27325377

  17. [Comparison and outcome of prevalence of concurrent diseases in patients with urological malignant diseases].

    PubMed

    Yoshinaga, Atsushi; Hayashi, Tetsuo; Yoshida, Soichiro; Ohno, Rena; Ishii, Nobuyuki; Terao, Toshiya; Watanabe, Toru; Yamada, Takumi

    2006-07-01

    We compared the prevalence of concurrent diseases (diabetes mellitus, hypertension, ischemic heart diseases and apoplexy) in patients with renal cell carcinoma, bladder carcinoma and prostatic carcinoma diagnosed in our department with that in all patients in our department analyzed using Mantel-Haenszel regression. In hypertension, there was a significantly high prevalence of patients with renal cell carcinoma (p < 0.05) in males and females, and prostatic carcinoma (p < 0.05). In diabetis mellitus, ischemic heart diseases and apoplexy, no apparent characteristic of prevalence was recognized. The close relationship between renal cell carcinoma, prostatic carcinoma and hypertension in this study corresponded with previous reports.

  18. Recent advances in the development of Aurora kinases inhibitors in hematological malignancies

    PubMed Central

    Choudary, Iqra; Barr, Paul M.; Friedberg, Jonathan

    2015-01-01

    Over the last two decades, since the discovery of Drosophila mutants in 1995, much effort has been made to understand Aurora kinase biology. Three mammalian subtypes have been identified thus far which include the Aurora A, B and C kinases. These regulatory proteins specifically work at the cytoskeleton and chromosomal structures between the kinetochores and have vital functions in the early phases of the mitotic cell cycle. Today, there are multiple phase I and phase II clinical trials as well as numerous preclinical studies taking place looking at Aurora kinase inhibitors in both hematologic and solid malignancies. This review focuses on the preclinical and clinical development of Aurora kinase inhibitors in hematological malignancy and discusses their therapeutic potential. PMID:26622997

  19. Invasive pneumococcal disease in patients with haematological malignancies before routine use of conjugate vaccines in Finland.

    PubMed

    Lindström, Vesa; Aittoniemi, Janne; Lyytikäinen, Outi; Klemets, Peter; Ollgren, Jukka; Silvennoinen, Raija; Nuorti, J Pekka; Sinisalo, Marjatta

    2016-01-01

    The baseline national invasive pneumococcal disease (IPD) incidence rate, serotype distribution and serotype coverage of pneumococcal vaccines were evaluated in patients with Hodgkin's and non-Hodgkin's lymphomas, myeloma and leukaemia within 1 year after haematological diagnosis during 1995-2002, before introduction of pneumococcal conjugate vaccines. Pneumococcal serotype distribution among these patients was different from serotypes causing IPD in the general population. The serotype coverages of PCV13 and PPSV23 were 57% and 64%, respectively, lower than in the general population. This reflects a higher predisposition to IPD in vaccinated patients with haematological malignancies and possibly less benefit of herd immunity gained with the wide use of pneumococcal conjugate vaccines in the general population. This data will be useful as a baseline for determining the future role of adult PCV vaccination in these patient groups.

  20. Second malignancies complicating Hodgkin's disease: a Southwest Oncology Group 10-year followup

    SciTech Connect

    Coltman, C.A. Jr.; Dixon, D.O.

    1982-04-01

    Thirty-two second malignancies (21 acute leukemias and 11 solid tumors) were identified among 659 patients with all stages of Hodgkin's disease treated by members of the Southwest Oncology Group. There were no leukemias and one solid tumor among 95 patients treated with radiotherapy alone. The actuarial risk of developing acute leukemia at 7 years was 6.2% for chemotherapy alone, 6.4% for combined modality, and 7.7% for salvage chemotherapy. The incidence of acute leukemia was higher (P . 0.002) among those whose treatment began at greater than or equal to 40 years of age. The actuarial risk of leukemia in that group was 20.7% at 7 years. These data are compatible with the hypothesis that chemotherapy alone, combined modality, and salvage chemotherapy have an equivalent oncogenic potential and that patients greater than or equal to 40 years of age have an enhanced susceptibility to these oncogenic stimuli.

  1. Neuroleptic malignant syndrome related to tetrabenazine introduction and haloperidol discontinuation in Huntington's disease.

    PubMed

    Mateo, D; Muñoz-Blanco, J L; Giménez-Roldán, S

    1992-02-01

    We describe the second reported case of neuroleptic malignant syndrome (NMS) related to tetrabenazine therapy in Huntington's disease. In the previously reported case, factors capable of potentiating NMS included a high dosage of tetrabenazine exceeding the accepted therapeutic range, and co-medication with the dopamine-synthesis inhibitor alpha-methylparatyrosine, while in the present case abrupt introduction of the drug and discontinuation of concomitant neuroleptics may have contributed to this important adverse reaction. Uneventful recovery occurred in both cases without the need for drugs specifically enhancing dopaminergic transmission, while rechallenge by tetrabenazine with conventional doses and slow upward titration was not followed by recurrence of the NMS. Tetrabenazine has proved to be a safe and frequently useful drug in the long-term treatment of approximately 400 dyskinetic patients. We believe that NMS related to this drug is rare, provided that it is properly administered.

  2. Less commonly used and emerging clinical applications of SPECT-CT in benign and malignant disease.

    PubMed

    Yap, Ki S; Patel, Chirag N; Chowdhury, Fahmid U; Scarsbrook, Andrew F

    2012-08-01

    The emergence of hybrid imaging, combining anatomical computed tomography (CT) and functional single-photon emission computed tomography (SPECT), has greatly expanded the armoury available to image disease. Integrated SPECT-CT is a dual-modality technique, which improves the sensitivity and specificity of existing radionuclide studies and enables characterization of equivocal findings detected by conventional imaging. There is a wide range of established and emerging clinical applications for SPECT-CT, which were reviewed in detail at a symposium organized by the British Institute of Radiology in March 2012. A series of articles were commissioned as an adjunct to the symposium and to raise awareness of the clinical utility of this technique. The focus of this article is on less commonly used and emerging clinical applications of hybrid SPECT-CT in a spectrum of benign and malignant conditions. The article will illustrate the incremental value of the technique in a variety of clinical applications.

  3. A case-control study of malignant and non-malignant respiratory disease among employees of a fiberglass manufacturing facility. II. Exposure assessment.

    PubMed Central

    Chiazze, L; Watkins, D K; Fryar, C; Kozono, J

    1993-01-01

    A case-control study of malignant and non-malignant respiratory disease among employees of the Owens-Corning Fiberglas Corporation's Newark, Ohio plant was undertaken. The aim was to determine the extent to which exposures to substances in the Newark plant environment, to non-workplace factors, or to a combination may play a part in the risk of mortality from respiratory disease among workers in this plant. A historical environmental reconstruction of the plant was undertaken to characterise the exposure profile for workers in this plant from its beginnings in 1934 to the end of 1987. The exposure profile provided estimates of cumulative exposure to respirable fibres, fine fibres, asbestos, talc, formaldehyde, silica, and asphalt fumes. Employment histories from Owens-Corning Fiberglas provided information on employment characteristics (duration of employment, year of hire, age at first hire) and an interview survey obtained information on demographic characteristics (birthdate, race, education, marital state, parent's ethnic background, and place of birth), lifetime residence, occupational and smoking histories, hobbies, and personal and family medical history. Matched, unadjusted odds ratios (ORs) were used to assess the association between lung cancer or non-malignant respiratory disease and the cumulative exposure history, demographic characteristics, and employment variables. Only the smoking variables and employment characteristics (year of hire and age at first hire) were statistically significant for lung cancer. For non-malignant respiratory disease, only the smoking variables were statistically significant in the univariate analysis. Of the variables entered into a conditional logistic regression model for lung cancer, only smoking (smoked for six months or more v never smoked: OR = 26.17, 95% confidence interval (95% CI) 3.316-206.5) and age at first hire (35 and over v less than 35: OR = 0.244, 95% CI 0.083-0.717) were statistically significant. There

  4. Long-Term Outcomes Among Older Patients Following Nonmyeloablative Conditioning and Allogeneic Hematopoietic Cell Transplantation for Advanced Hematologic Malignancies

    PubMed Central

    Sorror, Mohamed L.; Sandmaier, Brenda M.; Storer, Barry E.; Franke, Georg N.; Laport, Ginna G.; Chauncey, Thomas R.; Agura, Edward; Maziarz, Richard T.; Langston, Amelia; Hari, Parameswaran; Pulsipher, Michael A.; Bethge, Wolfgang; Sahebi, Firoozeh; Bruno, Benedetto; Maris, Michael B.; Yeager, Andrew; Petersen, Finn Bo; Vindeløv, Lars; McSweeney, Peter A.; Hübel, Kai; Mielcarek, Marco; Georges, George E.; Niederwieser, Dietger; Blume, Karl G.; Maloney, David G.; Storb, Rainer

    2011-01-01

    Context A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbidities. Objective To describe outcomes of patients ≥ 60 years. Design, Setting, and Participants From 1998 to 2008, 372 patients, 60–75 years old were enrolled in prospective clinical HCT trials at 18 collaborating institutions using conditioning with low-dose total body irradiation alone or combined with fludarabine 90 mg/m2 before related (n=184) or unrelated (n=188) donor transplants. Post-grafting immunosuppression included mycophenolate mofetil and a calcineurin inhibitor. Main Outcome Measures Overall and progression-free survivals were estimated by Kaplan-Meier method. Cumulative incidence estimates were calculated for acute and chronic GVHD, toxicities, achievement of full donor chimerism, complete remission, relapse, and non-relapse mortality. Hazard ratios (HR) were estimated from Cox regression models. Results Overall, 5-year cumulative incidences of non-relapse mortality and relapse were 27% (95% CI, 22%–32%) and 41% (95% CI, 36%–46%), respectively, leading to overall and progression-free 5-year survivals of 35% (95% CI, 30%–40%) and 32% (95% CI, 27%–37%), respectively. These outcomes were not statistically significantly different when stratified by age groups. Furthermore, increasing age was not associated with increases in acute or chronic graft-versus-host disease (GVHD) or organ toxicities. In multivariate models, HCT-CI scores of 1–2 [HR, 1.58 (95% CI,1.08–2.31)] and ≥3 [HR, 1.97 (95% CI,1.38–2.80)] were associated with worse survival compared to HCT-CI score of 0 (overall P = 0.003). Similarly, standard relapse risk [HR, 1.67 (95% CI, 1.10–2.54)] and high relapse risk [HR, 2.22 (95% CI, 1.43–3.43)] were associated with worse survival compared to low relapse risk (overall P = 0.0008). Conclusion Among patients aged 60

  5. Biomonitoring of organochlorines in women with benign and malignant breast disease

    SciTech Connect

    Siddiqui, M.K.J. . E-mail: mkjs@rediffmail.com; Anand, M.; Mehrotra, P.K.; Sarangi, R.; Mathur, N.

    2005-06-01

    Established risk factors for breast cancer explain breast cancer risk only partially. Organochlorines are considered to be a possible cause for hormone-dependent cancers. A hospital-based case-control study, the first from India, was conducted among 50 women undergoing surgery for breast disease to examine the association between organochlorine exposure and breast cancer risk. Blood, tumor, and surrounding adipose tissue of the breast were collected from the subjects with benign (control) and malignant breast (study) lesions and analyzed to determine organochlorine insecticides using a gas-liquid chromatograph equipped with an electron capture detector. The {alpha}, {beta}, {gamma}, and {delta} isomers of hexachlorocyclohexane (HCH), p,p'-dichlorodiphenyltrichloroethane (DDT), o,p'-DDT, p,p-dichlorodiphenyldichloroethylene, and p,p'-dichlorodiphenyldichloroethane were frequently detected in three specimens. Total HCH and total DDT levels were higher in the blood of the study group (25 cases) than in those of the controls (25 cases) with only {gamma}-HCH being significantly different (P0.05). However, both total HCH and total DDT were higher in the tumor tissues of the controls than in those of the study group; {gamma}-HCH was significantly different (P0.05). The level of total HCH ({alpha}-HCH was significantly different, P0.05) was higher in the breast adipose tissue of the study group, whereas total DDT was higher in the breast adipose tissue of the control group. The distribution of known confounders of breast cancer including age, body mass index, age at menarche and menopause, duration of breast feeding, and family history related to breast disease did not differ significantly between benign and malignant groups. This pilot study with limited statistical power does not support a positive association between exposure to organochlorines and risk of breast cancer but paves the way for a larger Indian study with greater statistical power encompassing different

  6. Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma: A Case Report and Literatures Review.

    PubMed

    Jing, Xu-Quan; Zhou, Lei; Sun, Xin-Dong; Yu, Jin-Ming; Meng, Xue

    2016-04-01

    Malignant pleural mesothelioma (MPM) is a lethal disease with poor prognosis. The combination of cisplatin and pemetrexed has been confirmed as the standard of care for nonoperable MPM. Data have shown that the adoption of pemetrexed maintenance therapy (PMT) following first-line treatment appears extremely promising.We describe a 57-year-old man diagnosed as advanced MPM. We treated this patient with PMT after first-line cisplatin-based bevacizumab-containing chemotherapy and residual tumor disappeared after 6 course of PMT. A perfect response and a long progression-free survival (PFS) were reached with tumor mass disappearing and 14 months duration of PFS.This case suggests that adding bevacizumab to standard first-line chemotherapy is feasible and that PMT could be promising and useful for treating advanced MPM. We further entail a review of the literature on the first-line treatment, continuation maintenance therapy, switch maintenance therapy, and second-line treatment of patients with advanced MPM.

  7. Expression of Human Herpesvirus-6 Antigens in Benign and Malignant Lymphoproliferative Diseases

    PubMed Central

    Luppi, Mario; Barozzi, Patrizia; Garber, Richard; Maiorana, Antonio; Bonacorsi, Goretta; Artusi, Tullio; Trovato, Raffaella; Marasca, Roberto; Torelli, Giuseppe

    1998-01-01

    Immunohistochemistry was used to look for the expression of human herpesvirus-6 (HHV-6) antigens in a well characterized series of benign, atypical, and malignant lymphoid lesions, which tested positive for the presence of HHV-6 DNA. A panel of specific antibodies against HHV-6 antigens, characteristic either of the early (p41) or late (p101K, gp106, and gp116) phases of the viral cycle, was applied to the lymphoid tissues from 15 non-Hodgkin’s lymphomas, 14 Hodgkin’s disease cases, 5 angioimmunoblastic lymphadenopathies with dysproteinemia, 14 reactive lymphadenopathies, and 2 cases of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). In lymphomatous tissues, the expression of late antigens was documented only in reactive cells, and mainly in plasma cells. Of interest, the expression of the early p41 antigen was detected in the so-called “mummified” Reed-Sternberg cells, in two Hodgkin’s disease cases. In reactive lymphadenopathies, the HHV-6 late antigen-expressing cells were plasma cells, histiocytes, and rare granulocytes distributed in interfollicular areas. In both cases of Rosai-Dorfman disease, the p101K showed an intense staining in follicular dendritic cells of germinal centers, whereas the gp106 exhibited an intense cytoplasmic reaction in the abnormal histiocytes, which represent the histological hallmark of the disease. The expression of HHV-6 antigens is tightly controlled in lymphoid tissues. The lack of HHV-6 antigen expression in neoplastic cells and the limited expression in degenerating Reed-Sternberg cells argue against a major pathogenetic role of the virus in human lymphomagenesis. The detection of a rather unique pattern of viral late antigen expression in Rosai-Dorfman disease suggests a possible pathogenetic involvement of HHV-6 in some cases of this rare lymphoproliferative disorder. PMID:9736030

  8. Recent advances in echocardiography for valvular heart disease

    PubMed Central

    Hahn, Rebecca

    2015-01-01

    Echocardiography is the imaging modality of choice for the assessment of patients with valvular heart disease. Echocardiographic advancements may have particular impact on the assessment and management of patients with valvular heart disease. This review will summarize the current literature on advancements, such as three-dimensional echocardiography, strain imaging, intracardiac echocardiography, and fusion imaging, in this patient population. PMID:26594349

  9. Second malignant neoplasms complicating Hodgkin's disease: the National Cancer Institute experience

    SciTech Connect

    Tester, W.J.; Kinsella, T.J.; Waller, B.; Makuch, R.W.; Kelley, P.A.; Glatstein, E.; DeVita, V.T.

    1984-07-01

    The medical records of all patients treated for Hodgkin's disease during the years 1964-1981 were reviewed. Four hundred seventy-three previously untreated patients were analyzed. Thirty-four subsequent second malignant neoplasms were observed in 33 patients among those treated for Hodgkin's disease. Eight cases of acute nonlymphocyctic leukemia, one case of chronic myeloid leukemia, three cases of non-Hodgkin's lymphoma, three cases of sarcoma, and 19 other tumors were identified. The ten-year estimated risk of leukemia by treatment was the following: radiotherapy only (0), chemotherapy only (0.02), initial combined radiotherapy-chemotherapy (0.06), and salvage combined radiotherapy-chemotherapy (0.09). The ten-year estimated risk of solid tumors was 0.07 overall, with all treatment groups associated with similar risks. Unlike some other reports, a greater risk of leukemia in patients who began treatment for Hodgkin's disease at age 40 or older was not found. However, a positive association was noted between increasing risk of solid tumors and increasing patient age.

  10. Exploring Spirituality in Family Caregivers of Patients With Primary Malignant Brain Tumors Across the Disease Trajectory

    PubMed Central

    Newberry, Alyssa G.; Jean Choi, Chien-Wen; Donovan, Heidi S.; Schulz, Richard; Bender, Catherine; Given, Barbara; Sherwood, Paula

    2013-01-01

    Purpose/Objectives To determine whether the perceived level of spirituality in family caregivers of patients with primary malignant brain tumors (PMBTs) changes across the disease trajectory. Design Ongoing descriptive, longitudinal study. Setting Southwestern Pennsylvania. Sample 50 family caregivers of patients with PMBT. Methods Caregivers and care recipients were recruited at time of diagnosis. Participants were interviewed at two subse-quent time points, four and eight months following diagnosis. Main Research Variables Care recipients’ symptoms, neuro-psychologic status, and physical function, as well as caregiver social support. Findings Results showed no significant difference in spirituality scores reported at baseline and eight months (p = 0.8), suggesting that spirituality may be a stable trait across the disease trajectory. Conclusions Spirituality remains relatively stable along the course of the disease trajectory. Reports of caregiver depressive symptoms and anxiety were lower when paired with higher reports of spirituality. Implications for Nursing Clinicians can better identify caregivers at risk for negative outcomes by identifying those who report lower levels of spirituality. Future interventions should focus on the development and implementation of interventions that provide protective buffers such as increased social support. Knowledge Translation Spirituality is a relatively stable trait. High levels of spirituality can serve as a protective buffer from negative mental health outcomes. Caregivers with low levels of spirituality may be at risk for greater levels of burden, anxiety, and stress. PMID:23615145

  11. Sustained response of malignant pericardial effusion to intrapericardial bevacizumab in an advanced lung cancer patient: a case report and literature review

    PubMed Central

    Chen, Dawei; Zhang, Yan; Shi, Fang; Li, Minghuan; Zhu, Hui; Kong, Li; Yu, Jinming

    2015-01-01

    Malignant pericardial effusion (MPCE) is a common complication of advanced malignant tumors, and interferes severely with patient prognosis and quality of life. The standard treatment for this complication is intracavitary perfusion of chemotherapeutic drugs, which is limited by unsatisfactory therapeutic effects and serious adverse events. We report a patient with MPCE who was treated with bevacizumab by pericardial perfusion, resulting in a complete response. This case supports the use of intrapericardial bevacizumab as a potential treatment for MPCE. PMID:26491350

  12. Advancing frontiers in Alzheimer's disease research

    SciTech Connect

    Glenner, G.G.; Wurtman, R.J.

    1987-01-01

    This book contain 16 chapters. Some of the titles are: Transmitter Alterations in Alzheimer's Disease: Relation to Cortical Dysfunction as Suggested by Positron Emission Tomography; Single-Photon Emission Computed Tomography in the Clinical Evaluation of Dementia; Clinical Diagnosis of Alzheimer's Disease; Down's Syndrome and Alzheimer's Disease: What is the Relationship; and Beta Protein: A Possible Marker for Alzheimer's Disease.

  13. Tolerability of different dosing regimens of bisphosphonates for the treatment of osteoporosis and malignant bone disease.

    PubMed

    Bobba, Raja S; Beattie, Karen; Parkinson, Bill; Kumbhare, Dinesh; Adachi, Jonathan D

    2006-01-01

    Bisphosphonates are the primary pharmacological agents used for the management of osteoporosis and hypercalcaemia of malignant bone disease. The efficacy of these agents in these two conditions has been demonstrated in many well designed trials published over the past 2 decades. The variety of bisphosphonates currently available to us provides a wide range of tolerability and dosing profiles thus necessitating a thorough comparison of the most recent oral and intravenous bisphosphonates to differentiate the clinical context in which they should be used. Despite the fact that bisphosphonates are generally well accepted, their tolerability is dependent on complications which encompass gastrointestinal (GI) and renal toxicity. Other adverse events include osteonecrosis of the jaw, arthralgias, flu-like symptoms and uveitis. Studies have shown that various dosing regimens are able to modulate these rates of toxicity. To maximise tolerability, the direction of future therapy will likely fall into a pattern of decreasing the frequency of administration of bisphosphonates, whether it is oral or intravenous formulations, thus improving patient adherence. To review the literature on different dosing regimens of various bisphosphonates and their associated tolerability, we searched MEDLINE for articles from 1975 to 2006. Oral bisphosphonates, in particular alendronate and risedronate, have been systematically evaluated with regards to GI toxicity. Overall tolerability with these oral formulations has found GI toxicity to be the primary adverse event of interest. Both alendronate and risedronate have been found to have similar rates of GI toxicity when compared with placebo. Mounting evidence has developed validating the use of intravenous ibandronate and zoledronic acid for the purpose of treating hypercalcaemia secondary to malignancy. Unique to all other bisphosphonates, ibandronate also has an oral form which has a similar GI-toxicity profile to placebo. In addition, no

  14. Intensity-Modulated Radiation Therapy for Anal Malignancies: A Preliminary Toxicity and Disease Outcomes Analysis

    SciTech Connect

    Pepek, Joseph M.; Willett, Christopher G.; Wu, Q. Jackie; Yoo, Sua; Clough, Robert W.; Czito, Brian G.

    2010-12-01

    Purpose: Intensity-modulated radiation therapy (IMRT) has the potential to reduce toxicities associated with chemoradiotherapy in the treatment of anal cancer. This study reports the results of using IMRT in the treatment of anal cancer. Methods and Materials: Records of patients with anal malignancies treated with IMRT at Duke University were reviewed. Acute toxicity was graded using the NCI CTCAEv3.0 scale. Overall survival (OS), metastasis-free survival (MFS), local-regional control (LRC) and colostomy-free survival (CFS) were calculated using the Kaplan-Meier method. Results: Forty-seven patients with anal malignancy (89% canal, 11% perianal skin) were treated with IMRT between August 2006 and September 2008. Median follow-up was 14 months (19 months for SCC patients). Median radiation dose was 54 Gy. Eight patients (18%) required treatment breaks lasting a median of 5 days (range, 2-7 days). Toxicity rates were as follows: Grade 4: leukopenia (7%), thrombocytopenia (2%); Grade 3: leukopenia (18%), diarrhea (9%), and anemia (4%); Grade 2: skin (93%), diarrhea (24%), and leukopenia (24%). The 2-year actuarial overall OS, MFS, LRC, and CFS rates were 85%, 78%, 90% and 82%, respectively. For SCC patients, the 2-year OS, MFS, LRC, and CFS rates were 100%, 100%, 95%, and 91%, respectively. Conclusions: IMRT-based chemoradiotherapy for anal cancer results in significant reductions in normal tissue dose and acute toxicities versus historic controls treated without IMRT, leading to reduced rates of toxicity-related treatment interruption. Early disease-related outcomes seem encouraging. IMRT is emerging as a standard therapy for anal cancer.

  15. Benign and Malignant Nodular Thyroid Disease in Acromegaly. Is a Routine Thyroid Ultrasound Evaluation Advisable?

    PubMed Central

    Reverter, Jordi L.; Fajardo, Carmen; Resmini, Eugenia; Salinas, Isabel; Mora, Mireia; Llatjós, Mariona; Sesmilo, Gemma; Rius, Ferran; Halperin, Irene; Webb, Susan M.; Ricart, Veronica; Riesgo, Pedro; Mauricio, Dídac; Puig-Domingo, Manel

    2014-01-01

    Data on the prevalence of benign and malignant nodular thyroid disease in patients with acromegaly is a matter of debate. In the last decade an increasing incidence of thyroid cancer has been reported. The aim of this study was to evaluate the prevalence of goiter, thyroid nodules and thyroid cancer in a large series of patients with acromegaly with a cross-sectional study with a control group. Six Spanish university hospitals participated. One hundred and twenty three patients (50% men; mean age 59±13 years; disease duration 6.7±7.2 years) and 50 controls (51% males, mean age 58±15 years) were studied. All participants underwent thyroid ultrasound and fine needle aspiration. Cytological analysis was performed in suspicious nodules between 0.5 and 1.0 cm and in all nodules greater than 1.0 cm. Goiter was more frequently found in patients than in controls (24.9 vs. 8.3%, respectively; p<0.001). Nodular thyroid disease as well as nodules greater than 1 cm were also more prevalent in acromegalic patients (64.6%, vs. 28.6%, p<0.05 and 53.3 vs. 28.6%, respectively; p<0.05), and all underwent fine needle aspiration. Suspicious cytology was detected in 4 patients and in none of the controls. After thyroidectomy, papillary thyroid carcinoma was confirmed in two cases (3.3% of patients with thyroid nodules), representing 1.6% of the entire group of patients with acromegaly (2.4% including a case with previously diagnosed papillary thyroid carcinoma). These data indicated that thyroid nodular disease and cancer are increased in acromegaly, thus justifying its routine ultrasound screening. PMID:25127456

  16. Benign and malignant nodular thyroid disease in acromegaly. Is a routine thyroid ultrasound evaluation advisable?

    PubMed

    Reverter, Jordi L; Fajardo, Carmen; Resmini, Eugenia; Salinas, Isabel; Mora, Mireia; Llatjós, Mariona; Sesmilo, Gemma; Rius, Ferran; Halperin, Irene; Webb, Susan M; Ricart, Veronica; Riesgo, Pedro; Mauricio, Dídac; Puig-Domingo, Manel

    2014-01-01

    Data on the prevalence of benign and malignant nodular thyroid disease in patients with acromegaly is a matter of debate. In the last decade an increasing incidence of thyroid cancer has been reported. The aim of this study was to evaluate the prevalence of goiter, thyroid nodules and thyroid cancer in a large series of patients with acromegaly with a cross-sectional study with a control group. Six Spanish university hospitals participated. One hundred and twenty three patients (50% men; mean age 59±13 years; disease duration 6.7±7.2 years) and 50 controls (51% males, mean age 58±15 years) were studied. All participants underwent thyroid ultrasound and fine needle aspiration. Cytological analysis was performed in suspicious nodules between 0.5 and 1.0 cm and in all nodules greater than 1.0 cm. Goiter was more frequently found in patients than in controls (24.9 vs. 8.3%, respectively; p<0.001). Nodular thyroid disease as well as nodules greater than 1 cm were also more prevalent in acromegalic patients (64.6%, vs. 28.6%, p<0.05 and 53.3 vs. 28.6%, respectively; p<0.05), and all underwent fine needle aspiration. Suspicious cytology was detected in 4 patients and in none of the controls. After thyroidectomy, papillary thyroid carcinoma was confirmed in two cases (3.3% of patients with thyroid nodules), representing 1.6% of the entire group of patients with acromegaly (2.4% including a case with previously diagnosed papillary thyroid carcinoma). These data indicated that thyroid nodular disease and cancer are increased in acromegaly, thus justifying its routine ultrasound screening.

  17. Treatment-related toxicities with Fluosol-DA 20% infusion during radiation in advanced head and neck malignancies

    SciTech Connect

    Campbell, B.H.; Janjan, N.A.; Byhardt, R.W.; Toohill, R.J. )

    1990-03-01

    Fluosol-DA 20%, a synthetic perfluorocarbon emulsion first developed as a blood substitute, is currently being investigated as a radiation sensitizer. Theoretically, an oxygen-carrying perfluorocarbon emulsion combined with oxygen inhalation might be able to increase tumor response by decreasing the relative proportion of hypoxic tumor cells. Twenty-one patients with advanced head and neck malignancies receiving primary radiation therapy were evaluated for treatment-related toxicity. Mucosal reactions and weight loss during treatment in the group of patients who received the perfluorocarbon emulsion and the group who did not were comparable. Late sequelae appeared comparable. No patient in either group who completed radiation therapy required an interruption of the treatment course. We conclude that Fluosol-DA 20% is a tolerated adjunct to primary radiation therapy. Further study is needed to determine whether the agent will improve local/regional tumor control.

  18. Genetic susceptibility to malignant pleural mesothelioma and other asbestos-associated diseases.

    PubMed

    Neri, Monica; Ugolini, Donatella; Dianzani, Irma; Gemignani, Federica; Landi, Stefano; Cesario, Alfredo; Magnani, Corrado; Mutti, Luciano; Puntoni, Riccardo; Bonassi, Stefano

    2008-01-01

    Exposure to asbestos fibers is a major risk factor for malignant pleural mesothelioma (MPM), lung cancer, and other non-neoplastic conditions, such as asbestosis and pleural plaques. However, in the last decade many studies have shown that polymorphism in the genes involved in xenobiotic and oxidative metabolism or in DNA repair processes may play an important role in the etiology and pathogenesis of these diseases. To evaluate the association between diseases linked to asbestos and genetic variability we performed a review of studies on this topic included in the PubMed database. One hundred fifty-nine citations were retrieved; 24 of them met the inclusion criteria and were evaluated in the review. The most commonly studied GSTM1 polymorphism showed for all asbestos-linked diseases an increased risk in association with the null genotype, possibly linked to its role in the conjugation of reactive oxygen species. Studies focused on GSTT1 null and SOD2 Ala16Val polymorphisms gave conflicting results, while promising results came from studies on alpha1-antitrypsin in asbestosis and MPO in lung cancer. Among genetic polymorphisms associated to the risk of MPM, the GSTM1 null genotype and two variant alleles of XRCC1 and XRCC3 showed increased risks in a subset of studies. Results for the NAT2 acetylator status, SOD2 polymorphism and EPHX activity were conflicting. Major limitations in the study design, including the small size of study groups, affected the reliability of these studies. Technical improvements such as the use of high-throughput techniques will help to identify molecular pathways regulated by candidate genes.

  19. Dysphagia in stroke, neurodegenerative disease, and advanced dementia.

    PubMed

    Altman, Kenneth W; Richards, Amanda; Goldberg, Leanne; Frucht, Steven; McCabe, Daniel J

    2013-12-01

    Aspiration risk from dysphagia increases with central and peripheral neurologic disease. Stroke, microvascular ischemic disease, a spectrum of neurodegenerative diseases, and advancing dementia all have unique aspects. However, there are distinct commonalities in this population. Increasing nutritional requirements to stave off oropharyngeal muscular atrophy and a sedentary lifestyle further tax the patient's abilities to safely swallow. This article reviews stroke, muscular dystrophy, myasthenia gravis, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and advanced dementia. Approaches to screening and evaluation, recognizing sentinel indicators of decline that increase aspiration risk, and options for managing global laryngeal dysfunction are also presented. PMID:24262965

  20. Dysphagia in stroke, neurodegenerative disease, and advanced dementia.

    PubMed

    Altman, Kenneth W; Richards, Amanda; Goldberg, Leanne; Frucht, Steven; McCabe, Daniel J

    2013-12-01

    Aspiration risk from dysphagia increases with central and peripheral neurologic disease. Stroke, microvascular ischemic disease, a spectrum of neurodegenerative diseases, and advancing dementia all have unique aspects. However, there are distinct commonalities in this population. Increasing nutritional requirements to stave off oropharyngeal muscular atrophy and a sedentary lifestyle further tax the patient's abilities to safely swallow. This article reviews stroke, muscular dystrophy, myasthenia gravis, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and advanced dementia. Approaches to screening and evaluation, recognizing sentinel indicators of decline that increase aspiration risk, and options for managing global laryngeal dysfunction are also presented.

  1. Regional hyperthermia in the treatment of clinically advanced, deep seated malignancy: results of a pilot study employing an annular array applicator

    SciTech Connect

    Sapozink, M.D.; Gibbs, F.A. Jr.; Gates, K.S.; Stewart, J.R.

    1984-06-01

    From October 1980 through December 1982, 46 patients were entered into a pilot study at the University of Utah Medical Center to assess the feasibility and safety of heating deep-seated, advanced, pelvic and abdominal malignancies with an annular array of electromagnetic wave (EMW) applicators. The patients, most of whom were heavily pretreated, were treated on a protocol in which most of the patients received combined hyperthermia and low dose X ray therapy. Discomforting local symptoms were the predominant treatment related acute side effects in 28 patients with pelvic disease, while systemic hyperthermia and associated symptoms were the predominant side effects in 18 patients with abdominal disease. Minor subacute toxicity was minimal and no serious treatment related, chronic toxicity was observed. The treatments of 22 patients with sufficiently detailed thermometry were analyzed at arbitrary index temperatures of 41/sup 0/C and 43/sup 0/C. Objective response rates in 22 evaluable patients were 67% and 9% for pelvic and abdominal sites respectively.

  2. Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases.

    PubMed

    Breitkreutz, R; Babylon, A; Hack, V; Schuster, K; Tokus, M; Böhles, H; Hagmüller, E; Edler, L; Holm, E; Dröge, W

    2000-01-01

    Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus (SIV) infection and may contribute to the development of cachexia. We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L-carnitine, i.e. an agent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice. In the mice, L-carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-treated group in the randomized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities. Further studies may be warranted to determine the effect of L-carnitine on the intramuscular GSH levels in cancer patients.

  3. Coloanal anastomosis in the management of benign and malignant rectal disease

    SciTech Connect

    Drake, D.B.; Pemberton, J.H.; Beart, R.W. Jr.; Dozois, R.R.; Wolff, B.G.

    1987-11-01

    The aim was to determine the efficacy, safety, and long-term clinical and functional results of coloanal anastomosis in patients with complicated benign and malignant rectal disease. Twenty-nine patients underwent coloanal or colopouch-anal anastomosis for either carcinoma of the rectum not technically amenable to conventional low anterior resection, severe radiation injury, large benign lower third tumors, or complications of previous operations. The mean age of the patients was 61 years and 82% were men. A diverting colostomy was constructed in 55% of the patients. The mean (+/- SEM) length of follow-up was 20 +/- 3 months. There was no operative mortality. Transient urinary retention, however, occurred in 40%, anastomotic stricture in 28%, and anastomotic leakage in 3.4%. Four patients (14%) could not have intestinal continuity restored and therefore were considered failures. The stool frequency for all remaining patients (N = 25) was 3 +/- 1 per day (mean +/- SEM) and did not vary with age, sex, or indication for operation. Complete continence was achieved by 84% of patients, but no patient was incapacitated by poor bowel function. In patients in whom a conventional colorectostomy is impractical or unwise, coloanal anastomosis is a safe and efficacious alternative operation that preserves anal continence.

  4. Comparative study of frequency of micronuclei in normal, potentially malignant diseases and oral squamous cell carcinoma

    PubMed Central

    Sangle, Varsha Ajit; Bijjaragi, Shobha; Shah, Nishat; Kangane, Suresh; Ghule, Hrishikesh M.; Rani, SR Ashwini

    2016-01-01

    Context: The assessment of micronuclei (MN) in exfoliated oral epithelial cells is a promising tool for the study of epithelial carcinogens and can be used to detect chromosome breakage or mitotic interference, thought to be relevant to carcinogenesis. Aims: To detect MN in exfoliated oral mucosal cells in individuals using various tobacco forms and also to detect frequency of MN in premalignant lesions and conditions (potentially malignant diseases [PMD's]) and oral squamous cell carcinoma (OSCC). To correlate frequency of MN in oral exfoliated cells in clinically diagnosed cases of OSCC followed by a histopathological grading. Materials and Methods: A total of 90 subjects (30 smokeless tobacco users, 30 smokers and 30 nontobacco users) consisted of clinically diagnosed cases of PMD's and OSCC were selected for the study. Cytosmears from the groups were stained with rapid Papanicolaou stain. MN was identified according to the Tolbert et al. criteria. Results: MN cells were found to be significantly higher in smokeless tobacco users than in smokers. The frequency of MN was three to four times higher in patients with OSCC as compared to patients in PMD's (P < 0.0001). The frequency of MN correlated with the histopathological grade was statistically significant. Conclusion: MN index can be used as a biomarker/screening test among the high-risk groups particularly the smokeless tobacco users and PMD's. MN can be a candidate to serve as a biomarker for prediction of the grade of OSCC. PMID:27003966

  5. Malignant catarrhal fever-like disease in sheep after intranasal inoculation with ovine herpesvirus-2.

    PubMed

    Li, Hong; O'Toole, Donal; Kim, Okjin; Oaks, J Lindsay; Crawford, Timothy B

    2005-03-01

    A malignant catarrhal fever (MCF)-like disease was induced experimentally in 3 sheep after aerosol inoculation with ovine herpesvirus-2 (OvHV-2). Each of 3 OvHV-2-negative sheep was nebulized with 2 ml of nasal secretions containing approximately 3.07 X 10(9) OvHV-2 DNA copies from a sheep experiencing an intensive viral-shedding episode. Ovine herpesvirus-2 DNA became detectable by polymerase chain reaction in the peripheral blood leukocytes of all 3 sheep within 3 days, and all 3 seroconverted between 6 and 8 days postinfection (PI). The sheep developed clinical signs, with copious mucopurulent nasal discharge and fever around 14 days PI. One of the 3 clinically affected sheep was euthanized at 18 days PI. Major lesions at necropsy were multifocal linear erosions and ulcers in mucosa of the cheeks, tongue, pharynx, and proximal esophagus and mild disseminated pneumonia. Microscopically, there was extensive moderate superficial histiocytic-lymphocytic rhinitis with epithelial dissociation and degeneration. Moderate multifocal histiocytic bronchointerstitial pneumonia was associated with loss of terminal bronchiolar epithelium. Lymphocytic vasculitis was present only in the lung. The remaining 2 sheep recovered clinically, approximately 25 days PI. The study revealed that clinical signs and lesions resembling MCF can develop when uninfected sheep are exposed to a high dose of aerosolized OvHV-2. PMID:15825499

  6. Secretory Products of Trichinella spiralis Muscle Larvae and Immunomodulation: Implication for Autoimmune Diseases, Allergies, and Malignancies.

    PubMed

    Sofronic-Milosavljevic, Ljiljana; Ilic, Natasa; Pinelli, Elena; Gruden-Movsesijan, Alisa

    2015-01-01

    Trichinella spiralis has the unique ability to make itself "at home" by creating and hiding in a new type of cell in the host body that is the nurse cell. From this immunologically privileged place, the parasite orchestrates a long-lasting molecular cross talk with the host through muscle larvae excretory-secretory products (ES L1). Those products can successfully modulate parasite-specific immune responses as well as responses to unrelated antigens (either self or nonself in origin), providing an anti-inflammatory milieu and maintaining homeostasis. It is clear, based on the findings from animal model studies, that T. spiralis and its products induce an immunomodulatory network (which encompasses Th2- and Treg-type responses) that may allow the host to deal with various hyperimmune-associated disorders as well as tumor growth, although the latter still remains unclear. This review focuses on studies of the molecules released by T. spiralis, their interaction with pattern recognition receptors on antigen presenting cells, and subsequently provoked responses. This paper also addresses the immunomodulatory properties of ES L1 molecules and how the induced immunomodulation influences the course of different experimental inflammatory and malignant diseases.

  7. Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases

    PubMed Central

    Breitkreutz, R; Babylon, A; Hack, V; Schuster, K; Tokus, M; Böhles, H; Hagmüller, E; Edler, L; Holm, E; Dröge, W

    2000-01-01

    Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus (SIV) infection and may contribute to the development of cachexia. We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L -carnitine, i.e. an agent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice. In the mice, L -carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-treated group in the randomized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities. Further studies may be warranted to determine the effect of L -carnitine on the intramuscular GSH levels in cancer patients. © 2000 Cancer Research Campaign PMID:10646895

  8. Secretory Products of Trichinella spiralis Muscle Larvae and Immunomodulation: Implication for Autoimmune Diseases, Allergies, and Malignancies.

    PubMed

    Sofronic-Milosavljevic, Ljiljana; Ilic, Natasa; Pinelli, Elena; Gruden-Movsesijan, Alisa

    2015-01-01

    Trichinella spiralis has the unique ability to make itself "at home" by creating and hiding in a new type of cell in the host body that is the nurse cell. From this immunologically privileged place, the parasite orchestrates a long-lasting molecular cross talk with the host through muscle larvae excretory-secretory products (ES L1). Those products can successfully modulate parasite-specific immune responses as well as responses to unrelated antigens (either self or nonself in origin), providing an anti-inflammatory milieu and maintaining homeostasis. It is clear, based on the findings from animal model studies, that T. spiralis and its products induce an immunomodulatory network (which encompasses Th2- and Treg-type responses) that may allow the host to deal with various hyperimmune-associated disorders as well as tumor growth, although the latter still remains unclear. This review focuses on studies of the molecules released by T. spiralis, their interaction with pattern recognition receptors on antigen presenting cells, and subsequently provoked responses. This paper also addresses the immunomodulatory properties of ES L1 molecules and how the induced immunomodulation influences the course of different experimental inflammatory and malignant diseases. PMID:26114122

  9. Hematologic malignancies

    SciTech Connect

    Hoogstraten, B.

    1986-01-01

    The principle aim of this book is to give practical guidelines to the modern treatment of the six important hematologic malignancies. Topics considered include the treatment of the chronic leukemias; acute leukemia in adults; the myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis/agnogenic myeloid metaplasia; Hodgkin's Disease; non-Hodgkin's lymphoma; and Multiple Myeloma.

  10. Advances in the diagnosis, treatment and prognosis of malignant pleural mesothelioma

    PubMed Central

    Zhang, Weiquan; Wu, Xinshu; Wu, Licun; Zhang, Weidong

    2015-01-01

    Malignant pleural mesothelioma (MPM) is a rare cancer originated from pleural mesothelial cells. MPM has been associated with long-term exposure to asbestos. The prognosis of MPM is poor due to the difficulty of making diagnosis in the early stage, the rapid progression, the high invasiveness and the lack of effective treatment. Although the incidence of MPM is low in China to date, it has a tendency to increase in the coming years. The variety of clinical features may cause the delay of diagnosis and high rate of misdiagnosis. The diagnosis of MPM is based on biopsy of the pleura and immunohistochemistry. As China has become the largest country in the consumption of asbestos, it would give rise to a new surge of MPM in the future. The current treatment of MPM is multimodality therapy including surgery, radiotherapy, chemotherapy and immunotherapy. Two surgical procedures are commonly applied: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). Three dimensional conformal radiotherapy is used to denote a spectrum of radiation planning and delivery techniques that rely on the 3D imaging to define the tumor. Cisplatin combined with pemetrexed (PEM) is the first-line chemotherapy for MPM. The principal targets in immunotherapy include T cells (Treg), CTLA-4 and PD-1. The diagnosis, treatment and prognosis still remain a major challenge for clinical research and will do so for years to come. PMID:26366399

  11. Treatment of locally advanced, high-grade, malignant tumors of major salivary glands

    SciTech Connect

    Reddy, S.P.; Marks, J.E.

    1988-04-01

    A retrospective review of 45 patients with Stage III and IV malignant tumors of the major salivary glands was undertaken to determine tumor control and patient survival after treatment with surgery and conventional ionizing-radiation therapy. Eight of the 23 patients received early postoperative radiotherapy after initial surgical resection, with a local control rate of 75%. Twelve of 23 patients had surgery as definitive treatment and the tumor recurred locally in all; seven of these 12 patients were subsequently salvaged by further surgery plus postoperative radiotherapy or by radiotherapy alone, with 58% ultimate local control. The remaining three patients had unresectable tumors at diagnosis and received radiation alone, with a local tumor control rate of 33%. Patients were also analyzed according to the extent of surgical resection prior to radiation therapy and according to radiation dose. Eighty-eight percent of completely resected, 50% of partially resected, and 44% of unresected tumors were locally controlled for an overall local control rate of 61%. The 5-year survival rate was significantly higher for patients with local tumor control than for patients who failed locally (31% vs. 0%).

  12. B-cell receptor signaling inhibitors for treatment of autoimmune inflammatory diseases and B-cell malignancies.

    PubMed

    Puri, Kamal D; Di Paolo, Julie A; Gold, Michael R

    2013-08-01

    B-cell receptor (BCR) signaling is essential for normal B-cell development, selection, survival, proliferation, and differentiation into antibody-secreting cells. Similarly, this pathway plays a key role in the pathogenesis of multiple B-cell malignancies. Genetic and pharmacological approaches have established an important role for the Spleen tyrosine kinase (Syk), Bruton's tyrosine kinase (Btk), and phosphatidylinositol 3-kinase isoform p110delta (PI3Kδ) in coupling the BCR and other BCRs to B-cell survival, migration, and activation. In the past few years, several small-molecule inhibitory drugs that target PI3Kδ, Btk, and Syk have been developed and shown to have efficacy in clinical trials for the treatment of several types of B-cell malignancies. Emerging preclinical data have also shown a critical role of BCR signaling in the activation and function of self-reactive B cells that contribute to autoimmune diseases. Because BCR signaling plays a major role in both B-cell-mediated autoimmune inflammation and B-cell malignancies, inhibition of this pathway may represent a promising new strategy for treating these diseases. This review summarizes recent achievements in the mechanism of action, pharmacological properties, and clinical activity and toxicity of these BCR signaling inhibitors, with a focus on their emerging role in treating lymphoid malignancies and autoimmune disorders.

  13. Multidetector CT Findings and Differential Diagnoses of Malignant Pleural Mesothelioma and Metastatic Pleural Diseases in Korea

    PubMed Central

    Kim, Yoon Kyung; Lee, Kyung Won; Yi, Chin A; Koo, Jin Mo; Jung, Soon-Hee

    2016-01-01

    Objective To compare the multidetector CT (MDCT) features of malignant pleural mesothelioma (MPM) and metastatic pleural disease (MPD). Materials and Methods The authors reviewed the MDCT images of 167 patients, 103 patients with MPM and 64 patients with MPD. All 167 cases were pathologically confirmed by sonography-guided needle biopsy of pleura, thoracoscopic pleural biopsy, or open thoracotomy. CT features were evaluated with respect to pleural effusion, pleural thickening, invasion of other organs, lung abnormality, lymphadenopathy, mediastinal shifting, thoracic volume decrease, asbestosis, and the presence of pleural plaque. Results Pleural thickening was the most common CT finding in MPM (96.1%) and MPD (93.8%). Circumferential pleural thickening (31.1% vs. 10.9%, odds ratio [OR] 3.670), thickening of fissural pleura (83.5% vs. 67.2%, OR 2.471), thickening of diaphragmatic pleura (90.3% vs. 73.4%, OR 3.364), pleural mass (38.8% vs. 23.4%, OR 2.074), pericardial involvement (56.3% vs. 20.3%, OR 5.056), and pleural plaque (66.0% vs. 21.9%, OR 6.939) were more frequently seen in MPM than in MPD. On the other hand, nodular pleural thickening (59.2% vs. 76.6%, OR 0.445), hilar lymph node metastasis (5.8% vs. 20.3%, OR 0.243), mediastinal lymph node metastasis (10.7% vs. 37.5%, OR 0.199), and hematogenous lung metastasis (9.7% vs. 29.2%, OR 0.261) were less frequent in MPM than in MPD. When we analyzed MPD from extrathoracic malignancy (EMPD) separately and compared them to MPM, circumferential pleural thickening, thickening of interlobar fissure, pericardial involvement and presence of pleural plaque were significant findings indicating MPM than EMPD. MPM had significantly lower occurrence of hematogenous lung metastasis, as compared with EMPD. Conclusion Awareness of frequent and infrequent CT findings could aid in distinguishing MPM from MPD. PMID:27390546

  14. Phase I Trial of Bortezomib and Concurrent External Beam Radiation in Patients With Advanced Solid Malignancies

    SciTech Connect

    Pugh, Thomas J.; Chen Changhu; Rabinovitch, Rachel; Eckhardt, S. Gail; Rusthoven, Kyle E.; Swing, Robyn; Raben, David

    2010-10-01

    Purpose: To determine the maximal tolerated dose of bortezomib with concurrent external beam radiation therapy in patients with incurable solid malignant tumors requiring palliative therapy. Methods and Materials: An open label, dose escalation, phase I clinical trial evaluated the safety of three dose levels of bortezomib administered intravenously (1.0 mg/m{sup 2}, 1.3 mg/m{sup 2}, and 1.6 mg/m{sup 2}/ dose) once weekly with concurrent radiation in patients with histologically confirmed solid tumors and a radiographically appreciable lesion suitable for palliative radiation therapy. All patients received 40 Gy in 16 fractions to the target lesion. Dose-limiting toxicity was the primary endpoint, defined as any grade 4 hematologic toxicity, any grade {>=}3 nonhematologic toxicity, or any toxicity requiring treatment to be delayed for {>=}2 weeks. Results: A total of 12 patients were enrolled. Primary sites included prostate (3 patients), head and neck (3 patients), uterus (1 patient), abdomen (1 patient), breast (1 patient), kidney (1 patient), lung (1 patient), and colon (1 patient). The maximum tolerated dose was not realized with a maximum dose of 1.6 mg/m{sup 2}. One case of dose-limiting toxicity was appreciated (grade 3 urosepsis) and felt to be unrelated to bortezomib. The most common grade 3 toxicity was lymphopenia (10 patients). Common grade 1 to 2 events included nausea (7 patients), infection without neutropenia (6 patients), diarrhea (5 patients), and fatigue (5 patients). Conclusions: The combination of palliative external beam radiation with concurrent weekly bortezomib therapy at a dose of 1.6 mg/m{sup 2} is well tolerated in patients with metastatic solid tumors. The maximum tolerated dose of once weekly bortezomib delivered concurrently with radiation therapy is greater than 1.6 mg/m{sup 2}.

  15. An Open-Label Study of a Novel JAK-inhibitor, INCB047986, Given in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2015-02-03

    Advanced Solid Tumors; Advanced Hodgkin's Lymphoma; Advanced Aggressive Non-Hodgkin's Lymphoma; Advanced Indolent Non-Hodgkin's Lymphoma; Advanced Pancreatic Adenocarcinoma; Advanced Triple-Negative Breast Cancer; Advanced Urothelial Carcinoma

  16. [Huntington's disease--advances in gene mapping].

    PubMed

    Nakamura, S

    1993-09-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor disturbance, cognitive loss, and psychiatric manifestations. It is inherited in an autosomal dominant fashion. The genetic defect causing HD was assigned to chromosome 4 in 1983 using polymorphic DNA markers in humans. Thereafter, a location cloning approach was pursued to isolate and characterize the HD gene. Recently, the Huntington's disease collaborative research group has isolated a new gene, IT 15, in 4p 16.3. IT 15 contains a polymorphic trinucleotide repeat that is expanded and unstable on HD chromosomes. A (CAG)n repeat longer than the normal range was observed on HD chromosomes from disease families. The (CAG)n repeat appears to be located within the coding sequence of a predicted 348 kd protein that is unrelated to any known gene.

  17. Advances in pediatric rhabdomyosarcoma characterization and disease model development.

    PubMed

    O'Brien, D; Jacob, A G; Qualman, S J; Chandler, D S

    2012-01-01

    Rhabdomyosarcoma (RMS), a form of soft tissue sarcoma, is one of the most common pediatric malignancies. A complex disease with at least three different subtypes, it is characterized by perturbations in a number of signaling pathways and genetic abnormalities. Extensive clinical studies have helped classify these tumors into high and low risk groups to facilitate different treatment regimens. Research into the etiology of the disease has helped uncover numerous potential therapeutic intervention points which can be tested on various animal models of RMS; both genetically modified models and tumor xenograft models. Taken together, there has been a marked increase in the survival rate of RMS patients but the highly invasive, metastatic forms of the disease continue to baffle researchers. This review aims to highlight and summarize some of the most important developments in characterization and in vivo model generation for RMS research, in the last few decades.

  18. Advances in pediatric rhabdomyosarcoma characterization and disease model development

    PubMed Central

    Brien, Dennis O’; Jacob, Aishwarya G.; Qualman, Stephen J.; Chandler, Dawn S.

    2014-01-01

    Summary Rhabdomyosarcoma (RMS), a form of soft tissue sarcoma, is one of the most common pediatric malignancies. A complex disease with at least three different subtypes, it is characterized by perturbations in a number of signaling pathways and genetic abnormalities. Extensive clinical studies have helped classify these tumors into high and low risk groups to facilitate different treatment regimens. Research into the etiology of the disease has helped uncover numerous potential therapeutic intervention points which can be tested on various animal models of RMS; both genetically modified models and tumor Xenograft models. Taken together, there has been a marked increase in the survival rate of RMS patients but the highly invasive, metastatic forms of the disease continue to baffle researchers. This review aims to highlight and summarize some of the most important developments in characterization and in vivo model generation for RMS research, in the last few decades. PMID:22127592

  19. p53 autoantibodies in patients with malignant mesothelioma: stability through disease progression

    PubMed Central

    Creaney, J; McLaren, B M; Stevenson, S; Musk, A W; Klerk, N de; Robinson, B W S; Lake, R A

    2001-01-01

    Malignant mesothelioma (MM) generally occurs as a pleural tumour, related to the inhalation of asbestos fibres. It is highly aggressive and largely unresponsive to treatment. The incidence of MM is particularly high in Western Australia because of the extensive blue asbestos mining operations that occurred in the north of the state until 1966. MM is unusual in that mutations in the tumour suppressor gene p53 are rarely observed, whilst over-expression of p53 protein is common. As the level of antibodies directed against p53 is thought to be of prognostic value in some cancers and as MM is known to be immunogenic, we studied a cohort of Western Australian patients to determine the prevalence of anti-p53 antibodies and their value as diagnostic markers or prognostic indicators. 6/88 (7%) of patients had high titres (>2 SD above the mean of controls) of anti-p53 antibodies. There was no correlation between antibody titre and survival. Although 3/38 (8%) of sera obtained from patients exposed to asbestos but prior to a diagnosis of MM contained antibodies, the same proportion of sera obtained from patients exposed to asbestos but who remained disease free also contained antibodies (2/40; 8%). Sera collected sequentially demonstrated a profound temporal stability in the titre of anti-p53 antibodies in patients with MM throughout the course of their illness. These results show that anti-p53 antibodies are observed only at a low frequency in the sera of MM patients and where they do occur, their elicitation is an early event that may be unrelated to antigen load. The occurrence of anti-p53 antibodies does not serve as either a useful prognostic or diagnostic indicator in MM. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11139313

  20. Subsequent Malignancies in Children Treated for Hodgkin's Disease: Associations With Gender and Radiation Dose

    SciTech Connect

    Constine, Louis S. Tarbell, Nancy; Hudson, Melissa M.; Schwartz, Cindy; Fisher, Susan G.; Muhs, Ann G. B.A.; Basu, Swati K.; Kun, Larry E.; Ng, Andrea; Mauch, Peter; Sandhu, Ajay; Culakova, Eva; Lyman, Gary; Mendenhall, Nancy

    2008-09-01

    Purpose: Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. Methods and Materials: A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). Results: We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Conclusions: Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.

  1. GNAS1 T393C polymorphism and disease progression in patients with malignant melanoma

    PubMed Central

    2010-01-01

    Background Once metastasized, despite a variety of therapeutic options, the prognosis of patients with malignant melanoma (MM) is still poor. Therefore, the search for reliable markers to identify patients with high risk of disease progression is of high clinical importance. We have recently shown that TT genotypes of the single-nucleotide polymorphism (SNP) T393C in the gene GNAS1 are significantly associated with better outcome in a variety of carcinomas. Patients In the present study we assessed whether the T393C SNP is also related to the clinical course in MM. 328 patients with MM were retrospectively genotyped and genotypes were correlated with clinical outcome. Results While the allele frequency in the MM group (fC 0.52) did not significantly differ from that of healthy blood donors, the T393C SNP was associated with tumor progression of MM. Carriers of the C-allele showed a significantly more severe tumor progression as estimated from the time period to develop metastasis (HR 2.2, 95% CI 1.1-3.2, p = 0.017). Proportions of 5-year metastasis-free intervals were 87.1% for TT genotypes and 66.0% for C-allele carriers. Moreover, multivariable Cox regression analysis including tumor stage and melanoma subtype proved the T393C polymorphism to be an independent factor for metastasis (p = 0.012). Conclusions In summary, the GNAS1 T393C SNP represents a genetic host factor for predicting tumor progression also in patients with MM; genotyping of this SNP may contribute to better define patients who could benefit from an early individualized therapy. PMID:21156401

  2. Advances in the prevention of Alzheimer's Disease

    PubMed Central

    Mangialasche, Francesca; Kivipelto, Miia

    2015-01-01

    Alzheimer's disease (AD), the leading cause of dementia, has reached epidemic proportions, with major social, medical and economical burdens. With no currently available curative treatments, both the World Health Organization and the G8 Dementia Summit recently identified dementia and AD prevention as a major public health priority. Dementia and AD have a wide range of risk factors (genetic, vascular/metabolic and lifestyle-related), which often co-occur and thus interact with each other. Previous intervention efforts aimed at preventing dementia and AD focused on the management of single risk factors, with relatively modest findings. Also, the effect of risk factors depends on age at exposure, indicating that the timing of preventive interventions needs to be carefully considered. In view of the complex multifactorial nature of AD, as well as its long pre-clinical (asymptomatic) phase, interventions simultaneously targeting multiple risk factors and disease mechanisms at an early stage of the disease are most likely to be effective. Three large European multidomain prevention trials have been launched with the goal of preventing cognitive decline, dementia and AD in older adults with different risk profiles. Pharmacological trials are also shifting towards prevention of Alzheimer dementia, by targeting at-risk individuals prior to the onset of cognitive symptoms. The current review will summarize and discuss the evidence on risk and protective factors from observational studies, ongoing lifestyle-related and pharmacological randomized controlled trials (RCTs), as well as future directions for dementia and AD prevention. PMID:26097723

  3. Short-Course Accelerated Radiotherapy in Palliative Treatment of Advanced Pelvic Malignancies: A Phase I Study

    SciTech Connect

    Caravatta, Luciana; Padula, Gilbert D.A.; Macchia, Gabriella; Ferrandina, Gabriella; Bonomo, Pierluigi; Deodato, Francesco; Massaccesi, Mariangela; Mignogna, Samantha; Tambaro, Rosa; Rossi, Marco; Flocco, Mariano; Scapati, Andrea; and others

    2012-08-01

    Purpose: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. Methods and Materials: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of {<=}3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). Results: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). Conclusions: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

  4. Biomarkers in inflammatory bowel disease: current practices and recent advances.

    PubMed

    Iskandar, Heba N; Ciorba, Matthew A

    2012-04-01

    Crohn's disease and ulcerative colitis represent the two main forms of the idiopathic chronic inflammatory bowel diseases (IBD). Currently available blood and stool based biomarkers provide reproducible, quantitative tools that can complement clinical assessment to aid clinicians in IBD diagnosis and management. C-reactive protein and fecal based leukocyte markers can help the clinician distinguish IBD from noninflammatory diarrhea and assess disease activity. The ability to differentiate between forms of IBD and predict risk for disease complications is specific to serologic tests including antibodies against Saccharomyces cerevisiae and perinuclear antineutrophil cytoplasmic proteins. Advances in genomic, proteomic, and metabolomic array based technologies are facilitating the development of new biomarkers for IBD. The discovery of novel biomarkers, which can correlate with mucosal healing or predict long-term disease course has the potential to significantly improve patient care. This article reviews the uses and limitations of currently available biomarkers and highlights recent advances in IBD biomarker discovery. PMID:22424434

  5. Advanced alveolar echinococcosis disease associated with Budd–Chiari syndrome

    PubMed Central

    Soyer, Vural; Ara, Cengiz; Yaylak, Faik; Sarıcı, Barış; Ozsoy, Mustafa; Koç, Okay; Yılmaz, Sezai

    2015-01-01

    Introduction Alveolar echinococceal disease of the liver is rare. Echinococcus multilocularis is responsible for the development of the related clinical conditions. Advanced disease may result with serious complications such as end stage liver disease and Budd–Chiari syndrome. Presentation of case In this presentation, a 28 years-old woman who was a case with advanced alveolar echinococcosis complicated with a Budd–Chiari syndrome and was performed successful living donor liver transplantation, has been demonstrated with clinical and radiological images. Discussion Initially there may be no clinical evidence of the disease in humans for years. Severity and fatality are the significant characteristics of the natural history. Extension to the surrounding tissues and metastasis of the parasitic mass may be observed. Prevention is essential in disease control. Serologic assay may identify the parasite. However, early diagnosis is rare. Staging is based on radiologic imaging. Some patients with advanced disease may require surgery. Hepatic resection and liver transplantation are accepted procedures in selected patients. Conclusion The importance of early diagnosis to prevent advanced complications such as development of Budd–Chiari syndrome and metastasis has been underlined. PMID:25600725

  6. Recent advances in small bowel diseases: Part II

    PubMed Central

    Thomson, Alan BR; Chopra, Angeli; Clandinin, Michael Tom; Freeman, Hugh

    2012-01-01

    As is the case in all areas of gastroenterology and hepatology, in 2009 and 2010 there were many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed, and the important advances in basic science as well as clinical applications were considered. In Part II we review six topics: absorption, short bowel syndrome, smooth muscle function and intestinal motility, tumors, diagnostic imaging, and cystic fibrosis. PMID:22807605

  7. The International Conference on Malignant Bowel Obstruction: A Meeting of the Minds to Advance Palliative Care Research

    PubMed Central

    Krouse, Robert S.

    2007-01-01

    There is a dearth of well-designed clinical research focusing on palliative care in cancer patients, especially those who are near the end of life. Reasons for this include ethical dilemmas in conducting such trials, communication barriers between specialties, and unclear standards for best care practices. To ensure that patients with incurable illnesses are offered the best available care, it is essential to develop and disseminate research methodologies well suited to this population. Given the multidimensional and culture-dependent nature of the end-of-life experience, it is necessary to adopt an interdisciplinary approach to developing research methods. As a means of initiating the process of palliative clinical research methodology development, malignant bowel obstruction (MBO) was used as a model to develop a research protocol. Although many treatment options for MBO have been proposed, existing literature offers little guidance with regard to algorithms for optimal management. To this end, an interdisciplinary summit of international leaders in quality-of-life research, ethno-cultural variability, palliative medicine, surgical oncology, gastroenterology, major consortium research, medical ethics, and patient advocacy/cancer survivors was convened in Pasadena, California, on November 12-13, 2004. Participants also represented the broad ethnic and racial perspectives required to develop culturally sensitive research methods. Consensus on methodological approaches was attained through vigorous debate. Using the conference-developed MBO model to implement trials will advance palliative care research. PMID:17544251

  8. NRF2 Mutation Confers Malignant Potential and Resistance to Chemoradiation Therapy in Advanced Esophageal Squamous Cancer1

    PubMed Central

    Shibata, Tatsuhiro; Kokubu, Akiko; Saito, Shigeru; Narisawa-Saito, Mako; Sasaki, Hiroki; Aoyagi, Kazuhiko; Yoshimatsu, Yuki; Tachimori, Yuji; Kushima, Ryoji; Kiyono, Tohru; Yamamoto, Masayuki

    2011-01-01

    Esophageal squamous cancer (ESC) is one of the most aggressive tumors of the gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT) has improved the clinical outcome, but the molecular background determining the effectiveness of therapy remains unknown. NRF2 is a master transcriptional regulator of stress adaptation, and gain of-function mutation of NRF2 in cancer confers resistance to stressors including anticancer therapy. Direct resequencing analysis revealed that Nrf2 gain-of-function mutation occurred recurrently (18/82, 22%) in advanced ESC tumors and ESC cell lines (3/10). The presence of Nrf2 mutation was associated with tumor recurrence and poor prognosis. Short hairpin RNA-mediated down-regulation of NRF2 in ESC cells that harbor only mutated Nrf2 allele revealed that themutant NRF2 conferred increased cell proliferation, attachment-independent survival, and resistance to 5-fluorouracil and γ-irradiation. Based on the Nrf2 mutation status, gene expression signatures associated with NRF2 mutation were extracted from ESC cell lines, and their potential utility for monitoring and prognosis was examined in a cohort of 33 pre-CRT cases of ESC. The molecular signatures of NRF2 mutation were significantly predictive and prognostic for CRT response. In conclusion, recurrent NRF2 mutation confers malignant potential and resistance to therapy in advanced ESC, resulting in a poorer outcome. Molecular signatures of NRF2 mutation can be applied as predictive markers of response to CRT, and efficient inhibition of aberrant NRF2 activation could be a promising approach in combination with CRT. PMID:21969819

  9. Simultaneous presentation of malignant peripheral nerve sheath tumor and moyamoya disease associated with neurofibromatosis type 1 in a child.

    PubMed

    Yoo, Sun Young; Hwang, Sun Mi; Lee, Min Kyung; Jo, Dae Sun; Hwang, Pyoung Han

    2015-01-01

    Neurofibromatosis type 1 (NF-1) is a rare hereditary disorder, which is inherited as an autosomal dominant trait. It is characterized by multiple caféau- lait spots of the skin, benign cutaneous neurofibromas, skeletal dysplasia and learning disability. The association of NF-1 with benign and malignant tumors is well established. The lifetime risk of patients with NF-1 developing malignant peripheral nerve sheath tumors (MPNSTs) has been estimated to be 8-13%. Such tumors can develop in any part of the body, but their occurrence in the gastrointestinal tract is rare. Patients with NF-1 have a wide spectrum of vascular abnormalities. Cerebrovascular lesions have been found in approximately 2.5% of children with NF1. We encountered a case of NF-1 with MPNSTs in the gastrointestinal tract and moyamoya disease.

  10. Simultaneous presentation of malignant peripheral nerve sheath tumor and moyamoya disease associated with neurofibromatosis type 1 in a child.

    PubMed

    Yoo, Sun Young; Hwang, Sun Mi; Lee, Min Kyung; Jo, Dae Sun; Hwang, Pyoung Han

    2015-01-01

    Neurofibromatosis type 1 (NF-1) is a rare hereditary disorder, which is inherited as an autosomal dominant trait. It is characterized by multiple caféau- lait spots of the skin, benign cutaneous neurofibromas, skeletal dysplasia and learning disability. The association of NF-1 with benign and malignant tumors is well established. The lifetime risk of patients with NF-1 developing malignant peripheral nerve sheath tumors (MPNSTs) has been estimated to be 8-13%. Such tumors can develop in any part of the body, but their occurrence in the gastrointestinal tract is rare. Patients with NF-1 have a wide spectrum of vascular abnormalities. Cerebrovascular lesions have been found in approximately 2.5% of children with NF1. We encountered a case of NF-1 with MPNSTs in the gastrointestinal tract and moyamoya disease. PMID:26690608

  11. Advances in diagnosis and management of salivary gland diseases.

    PubMed

    Rice, D H

    1984-02-01

    Salivary glands may be involved in a wide variety of diseases, which may be broadly grouped into (1) inflammatory, (2) noninflammatory, nonneoplastic and (3) neoplastic categories. Most inflammatory and noninflammatory, nonneoplastic diseases should be managed conservatively and symptomatically. The common exceptions are first-arch branchialcleft cysts and calculi. Neoplastic lesions always require resection if that is feasible. For benign tumors, simple excision with a cuff of normal tissue around it will usually suffice. The prevailing trend for treatment of malignant neoplasms is conservatism. No longer is the facial nerve routinely sacrificed. The resection done is dictated by the tumor size and the facial nerve is spared unless directly invaded. Postoperative radiation therapy is increasingly used.

  12. Kidney disease in children: latest advances and remaining challenges.

    PubMed

    Bertram, John F; Goldstein, Stuart L; Pape, Lars; Schaefer, Franz; Shroff, Rukshana C; Warady, Bradley A

    2016-03-01

    To mark World Kidney Day 2016, Nature Reviews Nephrology invited six leading researchers to highlight the key advances and challenges within their specialist field of paediatric nephrology. Here, advances and remaining challenges in the fields of prenatal patterning, acute kidney injury, renal transplantation, genetics, cardiovascular health, and growth and nutrition, are all discussed within the context of paediatric and neonatal patients with kidney disease. Our global panel of researchers describe areas in which further studies and clinical advances are needed, and suggest ways in which research in these areas should progress to optimize renal care and long-term outcomes for affected patients.

  13. Autosomal dominant polycystic kidney disease: recent advances in clinical management.

    PubMed

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C M

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 (th) century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 (st) century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  14. Advances in diagnostic testing for gastroesophageal reflux disease.

    PubMed

    Gawron, Andrew J; Hirano, Ikuo

    2010-08-14

    Gastroesophageal reflux disease (GERD) contributes substantially to morbidity and to costs in the United States health care system. The burden of this disease has resulted in attempts at improving diagnosis and characterizing patients. Numerous research and technical advances have enhanced our understanding of both the utility and limitations of a variety of diagnostic modalities. The purpose of this review is to highlight recent advances in GERD diagnostic testing and to discuss their implications for use in clinical practice. Topics addressed include esophageal pH monitoring, impedance testing, symptom association analyses, narrow-band imaging, and histopathology. PMID:20698036

  15. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed Central

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Summary Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them. PMID:27252737

  16. Autosomal dominant polycystic kidney disease: recent advances in clinical management

    PubMed Central

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C. M.

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 st century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  17. Advances in environmental and occupational diseases 2004.

    PubMed

    Frew, Anthony J

    2005-06-01

    2004 was another good year for publications on environmental and occupational disorders in our journal. The major focus is clearly on the environment and particularly on environmental risk factors for sensitization and asthma. There is a growing consensus that exposure to pets is good, provided there is enough of it. Low levels enhance sensitization, and higher levels protect against the consequences of that sensitization. Following on from previous work on cockroaches, we now see allergy to feral mice as an emergent problem--at least we now have the tools to study this properly. Emphasis seems to be swinging away from the outdoor environment as a cause of allergic disease and toward the indoor environment, which is, after all, where most of us spend most of our lives. New techniques for studying isocyanate allergy might kindle a revival of interest in the mechanisms of occupational asthma caused by low-molecular-weight compounds. But for all types of occupational allergy, prevention remains key, and it is good to see that comprehensive programs of allergen reduction can pay off in reduced rates of latex allergy in health care workers. Further work in the area of recombinant allergens is welcome but needs soon to be translated into new diagnostic and therapeutic strategies. This sector of allergy research remains vibrant, and the editors will continue to welcome outstanding contributions in this area.

  18. Mortality from non-malignant respiratory disease in the fibreglass manufacturing industry

    PubMed Central

    Chiazze, L; Watkins, D; Fryar, C; Fayerweather, W; Kozono, J; Biggs, V

    2002-01-01

    Objectives: To investigate the question of whether there is an association between workplace exposures and sociodemographic factors and mortality from non-malignant respiratory disease excluding influenza and pneumonia (NMRDxIP) among workers in a fibreglass wool manufacturing facility. Methods: A case-control study with cases and controls derived from deaths recorded from the Kansas City plant in the Owens Corning mortality surveillance system. The cases are defined as decedents with NMRDxIP as the underlying cause of death. Matched, unadjusted odds ratios (ORs) were used to assess any association between NMRDxIP and cumulative exposure history and sociodemographic factors individually. Matched, adjusted ORs were obtained by conditional logistic regression to estimate the effect of any one variable while controlling for the effect of all the others. Results: Results of the unadjusted analysis, considering variables one at a time, yielded no significant associations between NMRDxIP and any of the exposure or sociodemographic variables. The smoking OR was substantially increased (OR 5.09; 95%CI 0.65 to undeterimed). Also, there were no significant variables in a conditional logistic regression analysis in which all variables were simultaneously adjusted. ORs for respirable glass fibres were below unity at all concentrations of exposure in the adjusted analysis. For respirable silica there was no consistent relation across all exposure levels. The ORs increased through the first three exposure concentrations but decreased for the highest exposure. However, ORs although not significant, are greater than unity for all respirable concentrations of silica exposure. Conclusions: The findings for Kansas City show no association between respirable glass fibres and NMRDxIP. The adjusted ORs for all exposures to respirable fibres were less than unity. On the other hand, the ORs for silica exposures were all above unity although there was no clear dose-response relation and

  19. Role of Fractalkine/CX3CL1 and Its Receptor in the Pathogenesis of Inflammatory and Malignant Diseases with Emphasis on B Cell Malignancies

    PubMed Central

    Ferretti, Elisa; Pistoia, Vito; Corcione, Anna

    2014-01-01

    Fractalkine/CX3CL1, the only member of the CX3C chemokine family, exists as a membrane-anchored molecule as well as in soluble form, each mediating different biological activities. It is constitutively expressed in many hematopoietic and nonhematopoietic tissues such as endothelial and epithelial cells, lymphocytes, neurons, microglial osteoblasts. The biological activities of CX3CL1 are mediated by CX3CR1, that is expressed on different cell types such as NK cells, CD14+ monocytes, cytotoxic effector T cells, B cells, neurons, microglia, smooth muscle cells, and tumor cells. The CX3CL1/CX3CR1 axis is involved in the pathogenesis of several inflammatory cancer including various B cell malignancies. In tumors the interaction between cancer cells and cellular microenvironment creates a context that may promote tumor growth, increase tumor survival, and facilitate metastasis. Therefore the role of the CX3CL1/CX3CR1 has attracted interest as to the development of potential therapeutic approaches. Here we review the different effects of the CX3CL1/CX3CR1 axis in several inflammatory and neurodegenerative diseases and in cancer, with emphasis on human B cell lymphomas. PMID:24799766

  20. Subcutaneous nephrovesical bypass: Treatment for ureteral obstruction in advanced metastatic disease

    PubMed Central

    WANG, YUNYAN; WANG, GONGCHENG; HOU, PEIJIN; ZHUANG, HAIJUN; YANG, XIAOSONG; GU, SHUO; WANG, HENGBING; JI, LU; XU, ZONGYUAN; MENG, JUNSONG

    2015-01-01

    The aim of the present study was to explore the value of subcutaneous nephrovesical bypass (SNVB) for the treatment of ureteral obstruction due to pelvic metastatic disease. SNVB stents (n=30) were implanted in 24 patients with advanced metastatic disease between January 2008 and December 2012. Urinalysis, serum creatinine (SCr), glomerular filtration rate (GFR), quality of life (QoL) scores, and renal ultrasonography were evaluated at follow-up. The SNVB procedures were successful in all 24 patients. Patient follow-ups occurred at an average of 10.6 months. Preoperative hydronephrosis was eliminated in 16 cases (53.3%) and reduced in the remaining patients. Following surgery, SCr levels reduced significantly from 256±46 to 124±23 μmol/l (P<0.001). GFRs increased from 25±4.8 to 45±5.3 ml/min (P<0.01). The mean QoL scores were 3.4±1.4 preoperatively and 7.6±1.0 postoperatively (P<0.001). The results showed that SNVB is a minimally invasive, effective and safe procedure for patients with ureteral obstruction resulting from advanced malignant disease. As an alternative procedure to percutaneous nephrostomy, SNVB offers patients a better QoL. PMID:25435997

  1. Urinary Stone Disease: Advancing Knowledge, Patient Care, and Population Health.

    PubMed

    Scales, Charles D; Tasian, Gregory E; Schwaderer, Andrew L; Goldfarb, David S; Star, Robert A; Kirkali, Ziya

    2016-07-01

    Expanding epidemiologic and physiologic data suggest that urinary stone disease is best conceptualized as a chronic metabolic condition punctuated by symptomatic, preventable stone events. These acute events herald substantial future chronic morbidity, including decreased bone mineral density, cardiovascular disease, and CKD. Urinary stone disease imposes a large and growing public health burden. In the United States, 1 in 11 individuals will experience a urinary stone in their lifetime. Given this high incidence and prevalence, urinary stone disease is one of the most expensive urologic conditions, with health care charges exceeding $10 billion annually. Patient care focuses on management of symptomatic stones rather than prevention; after three decades of innovation, procedural interventions are almost exclusively minimally invasive or noninvasive, and mortality is rare. Despite these advances, the prevalence of stone disease has nearly doubled over the past 15 years, likely secondary to dietary and health trends. The NIDDK recently convened a symposium to assess knowledge and treatment gaps to inform future urinary stone disease research. Reducing the public health burden of urinary stone disease will require key advances in understanding environmental, genetic, and other individual disease determinants; improving secondary prevention; and optimal population health strategies in an increasingly cost-conscious care environment. PMID:26964844

  2. Delivery of Molecularly Targeted Therapy to Malignant Glioma, a Disease of the Whole Brain

    PubMed Central

    Agarwal, Sagar; Sane, Ramola; Oberoi, Rajneet; Ohlfest, John R.; Elmquist, William

    2016-01-01

    Glioblastoma multiforme, due to its invasive nature, can be considered a disease of the entire brain. Despite recent advances in surgery, radiotherapy and chemotherapy, current treatment regimens have only a marginal impact on patient survival. A crucial challenge faced by cancer researchers is to effectively deliver drugs to invasive glioma cells residing in a sanctuary within the central nervous system. The blood–brain barrier (BBB) restricts delivery of many small and large molecules into the brain. Drug delivery to the brain is further restricted by active efflux transporters present at the BBB, which transport drugs out of the brain back into the blood. Current clinical assessment of drug delivery and hence efficacy is based on the measured drug levels in the bulk tumor mass that is usually removed by surgery. Mounting evidence suggests that the inevitable relapse and lethality of glioblastoma multiforme is due to a failure to effectively treat invasive glioma cells. These invasive cells hide in areas of the brain that are shielded by an intact BBB where they continue to grow and give rise to the recurrent tumor. Effective delivery of chemotherapeutics to the invasive glioma cells is therefore critical, and long-term efficacy will depend upon the ability of a molecularly targeted agent to penetrate an intact and functional BBB throughout the entire brain. This review highlights the various aspects of the BBB, and also the brain–tumor-cell barrier, a barrier due to expression of efflux transporters in tumor cells, that together can significantly influence drug response. It then discusses the special challenge of glioma as a disease of the whole brain, which lends particular emphasis to the need to effectively deliver drugs across the BBB to reach both the central tumor and the invasive glioma cells. PMID:21676290

  3. Serum anti-p53 autoantibodies in pleural malignant mesothelioma, lung cancer and non-neoplastic lung diseases.

    PubMed

    Neri, Monica; Betta, Piergiacomo; Marroni, Paola; Filiberti, Rosangela; Cafferata, Mara; Mereu, Carlo; Ivaldi, Giampaolo; Montanaro, Fabio; Puntoni, Riccardo; Paganuzzi, Michela

    2003-02-01

    Alterations of the p53 gene may lead to the production of detectable autoantibodies (p53-Abs) in cancer patients. In order to evaluate the association of p53-Abs with pleuropulmonary diseases, four groups of subjects were analyzed by ELISA for serum p53-Abs, in the framework of a molecular epidemiologic study. Two of 30 pleural malignant mesothelioma patients (MM; 6.7%) and 8/48 lung cancer patients (LC; 16.7%) were seropositive, while all 51 healthy controls (HC) were negative. Two of 55 (3.6%) at-risk controls (RC) with non-malignant respiratory diseases were positive and were not subsequently diagnosed any cancer. The difference was statistically significant between LC and RC or HC (P = 0.01), but not between MM and any other group. No correlation was found with age, sex, cancer stage or histology, cigarette smoking or occupational exposure. A longer survival (not significant) was shown in seropositive LC but not in MM. p53 expression in tumor tissue was also evaluated in a subgroup of MM. In conclusion, the presence of detectable p53-Abs in serum was associated in a statistically significant proportion of cases with LC but only occasionally with MM. The longer survival among positive LC patients and the presence of two seropositive among patients with non-neoplastic respiratory diseases should be further investigated.

  4. Appraisals of Bangladeshi Medicinal Plants Used by Folk Medicine Practitioners in the Prevention and Management of Malignant Neoplastic Diseases

    PubMed Central

    Kabidul Azam, Md. Nur; Rahman, Md. Mizanur; Biswas, Samanta

    2016-01-01

    Cancer is a group of diseases which is categorized to differentiate into diverse cell types and move around in the body to sites of organogenesis that is key to the process of tumor genesis. All types of cancer fall into the group of malignant neoplastic diseases. In Bangladesh, cancer is now one of the foremost killer diseases and its personal, social, and economic bearing are huge. Plant-derived natural compounds (vincristine, vinblastine, etoposide, paclitaxel, camptothecin, topotecan, and irinotecan) are useful for the treatment of cancer. Since there is no extensive ethnobotanical research study in Bangladesh regarding the traditional uses of medicinal plants against neoplasms, therefore, a randomized ethnopharmacological surveys were carried out in 3 districts of Bangladesh to learn more about the usage of anticancer medicinal plants and their chemical constituents having antineoplastic activity. Comprehensive interviews were conducted to the folk medicine practitioners and medicinal plants as pointed out by them were photographed, collected, deposited, and identified at the Bangladesh National Herbarium. The various plant parts have been used by the healers which included whole plant, leaves, fruits, barks, roots, and seeds. This study evaluated considerable potential for discovery of novel compounds with less side effects in the management and prevention of malignancy in cancer. PMID:27382642

  5. Appraisals of Bangladeshi Medicinal Plants Used by Folk Medicine Practitioners in the Prevention and Management of Malignant Neoplastic Diseases.

    PubMed

    Kabidul Azam, Md Nur; Rahman, Md Mizanur; Biswas, Samanta; Ahmed, Md Nasir

    2016-01-01

    Cancer is a group of diseases which is categorized to differentiate into diverse cell types and move around in the body to sites of organogenesis that is key to the process of tumor genesis. All types of cancer fall into the group of malignant neoplastic diseases. In Bangladesh, cancer is now one of the foremost killer diseases and its personal, social, and economic bearing are huge. Plant-derived natural compounds (vincristine, vinblastine, etoposide, paclitaxel, camptothecin, topotecan, and irinotecan) are useful for the treatment of cancer. Since there is no extensive ethnobotanical research study in Bangladesh regarding the traditional uses of medicinal plants against neoplasms, therefore, a randomized ethnopharmacological surveys were carried out in 3 districts of Bangladesh to learn more about the usage of anticancer medicinal plants and their chemical constituents having antineoplastic activity. Comprehensive interviews were conducted to the folk medicine practitioners and medicinal plants as pointed out by them were photographed, collected, deposited, and identified at the Bangladesh National Herbarium. The various plant parts have been used by the healers which included whole plant, leaves, fruits, barks, roots, and seeds. This study evaluated considerable potential for discovery of novel compounds with less side effects in the management and prevention of malignancy in cancer. PMID:27382642

  6. Appraisals of Bangladeshi Medicinal Plants Used by Folk Medicine Practitioners in the Prevention and Management of Malignant Neoplastic Diseases.

    PubMed

    Kabidul Azam, Md Nur; Rahman, Md Mizanur; Biswas, Samanta; Ahmed, Md Nasir

    2016-01-01

    Cancer is a group of diseases which is categorized to differentiate into diverse cell types and move around in the body to sites of organogenesis that is key to the process of tumor genesis. All types of cancer fall into the group of malignant neoplastic diseases. In Bangladesh, cancer is now one of the foremost killer diseases and its personal, social, and economic bearing are huge. Plant-derived natural compounds (vincristine, vinblastine, etoposide, paclitaxel, camptothecin, topotecan, and irinotecan) are useful for the treatment of cancer. Since there is no extensive ethnobotanical research study in Bangladesh regarding the traditional uses of medicinal plants against neoplasms, therefore, a randomized ethnopharmacological surveys were carried out in 3 districts of Bangladesh to learn more about the usage of anticancer medicinal plants and their chemical constituents having antineoplastic activity. Comprehensive interviews were conducted to the folk medicine practitioners and medicinal plants as pointed out by them were photographed, collected, deposited, and identified at the Bangladesh National Herbarium. The various plant parts have been used by the healers which included whole plant, leaves, fruits, barks, roots, and seeds. This study evaluated considerable potential for discovery of novel compounds with less side effects in the management and prevention of malignancy in cancer.

  7. Testosterone in men with advanced liver disease: abnormalities and implications.

    PubMed

    Sinclair, Marie; Grossmann, Mathis; Gow, Paul J; Angus, Peter W

    2015-02-01

    Serum testosterone is reduced in up to 90% of men with cirrhosis, with levels falling as liver disease advances. Testosterone is an important anabolic hormone, with effects on muscle, bone, and hematopoiesis. Many of the features of advanced liver disease are similar to those seen in hypogonadal men, including sarcopenia, osteoporosis, gynecomastia, and low libido. However, the relative contribution of testosterone deficiency to the symptomatology of advanced liver disease has not been well established. More recently, it has been demonstrated that low testosterone in men with cirrhosis is associated with increased mortality, independent of the classically recognized prognostic factors, such as the Model for End-Stage Liver Disease score. Only several small clinical trials have examined the role of testosterone therapy in men with cirrhosis, none of which have resolved the issue of whether or not testosterone is beneficial. However, in men with organic hypogonadism due to structural hypothalamic-pituitary-testicular axis disease, testosterone therapy has been shown to improve muscle mass and bone mineral density, increase hemoglobin, and reduce insulin resistance. Despite initial concerns linking testosterone with hepatocellular carcinoma, more recent data suggest that this risk has been overstated. There is, therefore, now a strong rationale to assess the efficacy and safety of testosterone therapy in cirrhosis in well-designed randomized controlled trials. PMID:25087838

  8. Advances in Diagnosis of Respiratory Diseases of Small Ruminants

    PubMed Central

    Chakraborty, Sandip; Kumar, Amit; Tiwari, Ruchi; Rahal, Anu; Malik, Yash; Dhama, Kuldeep; Pal, Amar; Prasad, Minakshi

    2014-01-01

    Irrespective of aetiology, infectious respiratory diseases of sheep and goats contribute to 5.6 percent of the total diseases of small ruminants. These infectious respiratory disorders are divided into two groups: the diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, and diseases of lower respiratory tract, namely, peste des petits ruminants (PPR), parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others. Depending upon aetiology, many of them are acute and fatal in nature. Early, rapid, and specific diagnosis of such diseases holds great importance to reduce the losses. The advanced enzyme-linked immunosorbent assays (ELISAs) for the detection of antigen as well as antibodies directly from the samples and molecular diagnostic assays along with microsatellites comprehensively assist in diagnosis as well as treatment and epidemiological studies. The present review discusses the advancements made in the diagnosis of common infectious respiratory diseases of sheep and goats. It would update the knowledge and help in adapting and implementing appropriate, timely, and confirmatory diagnostic procedures. Moreover, it would assist in designing appropriate prevention protocols and devising suitable control strategies to overcome respiratory diseases and alleviate the economic losses. PMID:25028620

  9. Advanced drug delivery and targeting technologies for the ocular diseases

    PubMed Central

    Barar, Jaleh; Aghanejad, Ayuob; Fathi, Marziyeh; Omidi, Yadollah

    2016-01-01

    Introduction: Ocular targeted therapy has enormously been advanced by implementation of new methods of drug delivery and targeting using implantable drug delivery systems (DDSs) or devices (DDDs), stimuli-responsive advanced biomaterials, multimodal nanomedicines, cell therapy modalities and medical bioMEMs. These technologies tackle several ocular diseases such as inflammation-based diseases (e.g., scleritis, keratitis, uveitis, iritis, conjunctivitis, chorioretinitis, choroiditis, retinitis, retinochoroiditis), ocular hypertension and neuropathy, age-related macular degeneration and mucopolysaccharidosis (MPS) due to accumulation of glycosaminoglycans (GAGs). Such therapies appear to provide ultimate treatments, even though much more effective, yet biocompatible, noninvasive therapies are needed to control some disabling ocular diseases/disorders. Methods: In the current study, we have reviewed and discussed recent advancements on ocular targeted therapies. Results: On the ground that the pharmacokinetic and pharmacodynamic analyses of ophthalmic drugs need special techniques, most of ocular DDSs/devices developments have been designed to localized therapy within the eye. Application of advanced DDSs such as Subconjunctival insert/implants (e.g., latanoprost implant, Gamunex-C), episcleral implant (e.g., LX201), cationic emulsions (e.g., Cationorm™, Vekacia™, Cyclokat™), intac/punctal plug DDSs (latanoprost punctal plug delivery system, L-PPDS), and intravitreal implants (I-vitaion™, NT-501, NT- 503, MicroPump, Thethadur, IB-20089 Verisome™, Cortiject, DE-102, Retisert™, Iluvein™ and Ozurdex™) have significantly improved the treatment of ocular diseases. However, most of these DDSs/devices are applied invasively and even need surgical procedures. Of these, use of de novo technologies such as advanced stimuli-responsive nanomaterials, multimodal nanosystems (NSs)/nanoconjugates (NCs), biomacromolecualr scaffolds, and bioengineered cell therapies

  10. Recent advances in autosomal-dominant polycystic kidney disease.

    PubMed

    Rangan, G K; Tchan, M C; Tong, A; Wong, A T Y; Nankivell, B J

    2016-08-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults, affecting one in every 1000 Australians. It is caused by loss-of-function heterozygous mutations in either PKD1 or PKD2 , which encode the proteins, polycystin-1 and polycystin-2 respectively. The disease hallmark is the development of hundreds of microscopic fluid-filled cysts in the kidney during early childhood, which grow exponentially and continuously through life at varying rates (between 2% and 10% per year), causing loss of normal renal tissue and up to a 50% lifetime risk of dialysis-dependent kidney failure. Other systemic complications include hypertensive cardiac disease, hepatic cysts, intracranial aneurysms, diverticular disease and hernias. Over the last two decades, advances in the genetics and pathogenesis of this disease have led to novel treatments that reduce the rate of renal cyst growth and may potentially delay the onset of kidney failure. New evidence indicates that conventional therapies (such as angiotensin inhibitors and statins) have mild attenuating effects on renal cyst growth and that systemic levels of vasopressin are critical for promoting renal cyst growth in the postnatal period. Identifying and integrating patient-centred perspectives in clinical trials is also being advocated. This review will provide an update on recent advances in the clinical management of ADPKD. PMID:27553994

  11. Recent advances in autosomal-dominant polycystic kidney disease.

    PubMed

    Rangan, G K; Tchan, M C; Tong, A; Wong, A T Y; Nankivell, B J

    2016-08-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults, affecting one in every 1000 Australians. It is caused by loss-of-function heterozygous mutations in either PKD1 or PKD2 , which encode the proteins, polycystin-1 and polycystin-2 respectively. The disease hallmark is the development of hundreds of microscopic fluid-filled cysts in the kidney during early childhood, which grow exponentially and continuously through life at varying rates (between 2% and 10% per year), causing loss of normal renal tissue and up to a 50% lifetime risk of dialysis-dependent kidney failure. Other systemic complications include hypertensive cardiac disease, hepatic cysts, intracranial aneurysms, diverticular disease and hernias. Over the last two decades, advances in the genetics and pathogenesis of this disease have led to novel treatments that reduce the rate of renal cyst growth and may potentially delay the onset of kidney failure. New evidence indicates that conventional therapies (such as angiotensin inhibitors and statins) have mild attenuating effects on renal cyst growth and that systemic levels of vasopressin are critical for promoting renal cyst growth in the postnatal period. Identifying and integrating patient-centred perspectives in clinical trials is also being advocated. This review will provide an update on recent advances in the clinical management of ADPKD.

  12. Recent advances in small bowel diseases: Part I

    PubMed Central

    Thomson, Alan BR; Chopra, Angeli; Clandinin, Michael Tom; Freeman, Hugh

    2012-01-01

    As is the case in all parts of gastroenterology and hepatology, there have been many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed for 2008 and 2009, and the important advances in basic science as well as clinical applications were considered. In Part I of this Editorial Review, seven topics are considered: intestinal development; proliferation and repair; intestinal permeability; microbiotica, infectious diarrhea and probiotics; diarrhea; salt and water absorption; necrotizing enterocolitis; and immunology/allergy. These topics were chosen because of their importance to the practicing physician. PMID:22807604

  13. Advances in non-dopaminergic treatments for Parkinson's disease

    PubMed Central

    Stayte, Sandy; Vissel, Bryce

    2014-01-01

    Since the 1960's treatments for Parkinson's disease (PD) have traditionally been directed to restore or replace dopamine, with L-Dopa being the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has resulted in extensive efforts to develop new therapies that work in ways other than restoring or replacing dopamine. Here we describe newly emerging non-dopaminergic therapeutic strategies for PD, including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors, and gene therapies. We provide a detailed account of their success in animal models and their translation to human clinical trials. We then consider how advances in understanding the mechanisms of PD, genetics, the possibility that PD may consist of multiple disease states, understanding of the etiology of PD in non-dopaminergic regions as well as advances in clinical trial design will be essential for ongoing advances. We conclude that despite the challenges ahead, patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable. PMID:24904259

  14. Laboratory Diagnosis of Lyme Disease - Advances and Challenges

    PubMed Central

    Marques, Adriana R.

    2015-01-01

    Synopsis Lyme disease is the most common tick-borne illness in the United States and Europe. Culture for B. burgdorferi is not routinely available. PCR can be helpful in synovial fluid of patients with Lyme arthritis. The majority of laboratory tests performed for the diagnosis of Lyme disease are based on detection of the antibody responses against B. burgdorferi in serum. The sensitivity of antibody-based tests increases with the duration of the infection, and patients who present very early in their illness are more likely to have a negative result. Patients with erythema migrans should receive treatment based on the clinical diagnosis. The current Centers for Disease Control and Prevention recommendations for serodiagnosis of Lyme disease is a 2-tiered algorithm, an initial enzyme immunoassay (EIA) followed by separate IgM and IgG Western blots if the first EIA test result is positive or borderline. The IgM result is only relevant for patients with illness duration of less than a month. While the 2-tier algorithm works well for later stages of the infection, it has low sensitivity during early infection. A major advance has been the discovery of VlsE and its C6 peptide as markers of antibody response in Lyme disease. Specificity is extremely important in Lyme disease testing, as the majority of tests are being performed in situations with low likelihood of the disease, a situation where a positive result is more likely to be a false positive. Current assays do not distinguish between active and inactive infection, and patients may continue to be seropositive for years. There is a need to simplify the testing algorithm for Lyme disease, improving sensitivity in early disease while still maintaining high specificity and providing information about the stage of infection. The development of a point of care assay and biomarkers for active infection would be major advances for the field. PMID:25999225

  15. Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases.

    PubMed

    Slatter, M A; Boztug, H; Pötschger, U; Sykora, K-W; Lankester, A; Yaniv, I; Sedlacek, P; Glogova, E; Veys, P; Gennery, A R; Peters, C

    2015-12-01

    An increasing number of children with non-malignant diseases can be cured by allogeneic haematopoietic stem cell transplantation (HSCT). Treosulfan (L-treitol-1,4-bis-methanesulfonate) is being used more frequently for conditioning, owing to its' lower toxicity profile compared with conventional myeloablative regimens. A retrospective analysis was performed of children registered in the EBMT database, who received treosulfan before HSCT between January 2005 and 2010, to identify possible dose-related toxicity and determine the incidence of engraftment, treatment-related mortality and overall survival (OS). Results from 316 transplants from 11 different countries are presented. Ninety-five (30%) were under 1 year of age at the time of transplant. OS was 83% and event-free survival was 76%; 3-year OS and event-free survival of infants below 1 year were 79% and 73%, respectively. No association was found with age at transplant, dose of treosulfan given, other agents used in combination with treosulfan, donor type, stem cell source, or second or subsequent transplant. In this report of the largest number of children to date receiving treosulfan for non-malignant diseases, treosulfan is shown to be a safe and effective agent even for those under 1 year of age at the time of transplant. Further prospective studies are needed using precisely defined protocols with pharmacokinetic monitoring and detailed chimerism analysis. In addition, long-term studies will be vital to determine long-term effects, for example, on fertility in comparison with other regimens.

  16. A survey of human T-cell leukaemia virus type I antibodies in patients with malignant disease in the Witwatersrand area.

    PubMed

    Dansey, R D; Mansoor, N; Cohn, R J; MacDougall, L G; Bezwoda, W R

    1986-10-11

    The prevalence of antibodies to human T-cell leukaemia virus type I in Africa ranges from 2% to 21% according to the geographical area surveyed. Most studies suggest that the background infection rate in children is low. In paediatric patients with malignant disease in the Witwatersrand area the prevalence is low (1%), whereas a seemingly high rate is found in healthy black children from a restricted rural area (7%). Further, the antibody prevalence in adult whites with lymphoproliferative disease is low (1%) compared with that in blacks with malignant disease (6%). There also appears to be a higher prevalence of positive results in black women (7%) than in black men (4%).

  17. [Research advances in pediatric nonalcoholic fatty liver disease].

    PubMed

    Dai, Dong-Ling

    2015-01-01

    In recent years, nonalcoholic fatty liver disease (NAFLD) has increased because of the growing prevalence of obesity and overweight in the pediatric population. It has become the most common form of chronic liver diseases in children and the related research on NAFLD is expanded. The "two-hit" and "multiple hit" hypothesis have been widely accepted, and some research has shown that genetic, diet structure and environmental factors appear to play a crucial role in the development of pediatric NAFLD. Though it is expected by researchers, there is not an available satisfactory noninvasive marker for the diagnosis of this disease. Fortunately, some new non-invasive prediction scores for pediatric NAFLD have been developed. There is currently no established special therapy, and lifestyle intervention should be adequate for most cases of NAFLD in children. This article reviews the advances in the current knowledge and ideas concerning pediatric NAFLD, and discusses the diagnosis, perspective therapies and scoring methods for this disease.

  18. Population pharmacokinetics and dosing optimization of teicoplanin in children with malignant haematological disease

    PubMed Central

    Zhao, Wei; Zhang, Daolun; Storme, Thomas; Baruchel, André; Declèves, Xavier; Jacqz-Aigrain, Evelyne

    2015-01-01

    Aim Children with haematological malignancy represent an identified subgroup of the paediatric population with specific pharmacokinetic parameters. In these patients, inadequate empirical antibacterial therapy may result in infection-related morbidity and increased mortality, making optimization of the dosing regimen essential. As paediatric data are limited, our aim was to evaluate the population pharmacokinetics of teicoplanin in order to define the appropriate dosing regimen in this high risk population. Methods The current dose of teicoplanin was evaluated in children with haematological malignancy. Population pharmacokinetics of teicoplanin were analyzed using nonmem software. The dosing regimen was optimized based on the final model. Results Eighty-five children (age range 0.5 to 16.9 years) were included. Therapeutic drug monitoring and opportunistic samples (n = 143) were available for analysis. With the current recommended dose of 10 mg kg–1 day–1, 41 children (48%) had sub-therapeutic steady-state trough concentrations (Css,min<10 mg l–1). A two compartment pharmacokinetic model with first order elimination was developed. Systematic covariate analysis identified that bodyweight (size) and creatinine clearance significantly influenced teicoplanin clearance. The model was validated internally. Its predictive performance was further confirmed in an external validation. In order to reach the target AUC of 750 mg l–1 h 18 mg kg–1 was required for infants, 14 mg kg–1 for children and 12 mg kg–1 for adolescents. A patient-tailored dose regimen was further developed and reduced variability in AUC and Css,min values compared with the mg kg–1 basis dose, making the modelling approach an important tool for dosing individualization. Conclusions This first population pharmacokinetic study of teicoplanin in children with haematological malignancy provided evidence-based support to individualize teicoplanin therapy in this vulnerable

  19. [Gene therapy for hereditary ophthalmological diseases: Advances and future perspectives].

    PubMed

    Chacón-Camacho, Óscar Francisco; Astorga-Carballo, Aline; Zenteno, Juan Carlos

    2015-01-01

    Gene therapy is a promising new therapeutic strategy that could provide a novel and more effective way of targeting hereditary ophthalmological diseases. The eye is easily accessible, highly compartmentalized, and an immune-privileged organ that gives advantages as an ideal gene therapy target. Recently, important advances in the availability of various intraocular vector delivery routes and viral vectors that are able to efficiently transduce specific ocular cell types have been described. Gene therapy has advanced in some retinal inherited dystrophies; in this way, preliminary success is now being reported for the treatment of Leber congenital amaurosis (LCA). This review will provide an update in the field of gene therapy for the treatment of ocular inherited diseases.

  20. Recent advances in understanding of chronic kidney disease

    PubMed Central

    Yamaguchi, Junna; Tanaka, Tetsuhiro; Nangaku, Masaomi

    2015-01-01

    Chronic kidney disease (CKD) is defined as any condition that causes reduced kidney function over a period of time. Fibrosis, tubular atrophy and interstitial inflammation are the hallmark of pathological features in CKD. Regardless of initial insult, CKD has some common pathways leading CKD to end-stage kidney disease, including hypoxia in the tubulointerstitium and proteinuria. Recent advances in genome editing technologies and stem cell research give great insights to understand the pathogenesis of CKD, including identifications of the origins of renal myofibroblasts and tubular epithelial cells upon injury. Environmental factors such as hypoxia, oxidative stress, and epigenetic factors in relation to CKD are also discussed. PMID:26937272

  1. Malignant pleural mesothelioma.

    PubMed

    Boutin, C; Schlesser, M; Frenay, C; Astoul, P

    1998-10-01

    The incidence of malignant pleural mesothelioma (MPM) has risen for some decades and is expected to peak between 2010 and 2020. Up to now, no single treatment has been proven to be effective and death usually occurs within about 12-17 months after diagnosis. Perhaps because of this poor prognosis, early screening has incited little interest. However, certain forms may have a better prognosis when diagnosed early and treated by multimodal therapy or intrapleural immunotherapy. Diagnosis depends foremost on histological analysis of samples obtained by thoracoscopy. This procedure allows the best staging of the pleural cavity with an attempt to detect visceral pleural involvement, which is one of the most important prognostic factors. Although radiotherapy seems necessary and is efficient in preventing the malignant seeding after diagnostic procedures in patients, there has been no randomized phase III study showing the superiority of any treatment compared with another. However, for the early-stage disease (stage I) a logical therapeutic approach seems to be neoadjuvant intrapleural treatment using cytokines. For more advanced disease (stages II and III) resectability should be discussed with the thoracic surgeons and a multimodal treatment combining surgery, radiotherapy and chemotherapy should be proposed for a randomized controlled study. Palliative treatment is indicated for stage IV. In any case, each patient should be enrolled in a clinical trial.

  2. A phase I trial of bryostatin 1 in patients with advanced malignancy using a 24 hour intravenous infusion.

    PubMed Central

    Jayson, G. C.; Crowther, D.; Prendiville, J.; McGown, A. T.; Scheid, C.; Stern, P.; Young, R.; Brenchley, P.; Chang, J.; Owens, S.

    1995-01-01

    Bryostatin 1 is a macrocyclic lactone derived from the marine invertebrate Bugula neritina. In vitro, bryostatin 1 activates protein kinase C (PKC), induces the differentiation of a number of cancer cell lineages, exhibits anti-tumour activity and augments the response of haemopoietic cells to certain growth factors. In vivo, bryostatin 1 is also immunomodulatory, but the range of tumours which respond to bryostatin 1 in xenograft tumour models is mostly the same as the in vitro tumour types, suggesting a direct mode of action. Nineteen patients with advanced malignancy were entered into a phase I study in which bryostatin 1 was given as a 24 h intravenous infusion, weekly, for 8 weeks. Myalgia was the dose-limiting toxicity and the maximum tolerated dose was 25 micrograms m-2 per week. The myalgia was cumulative and dose related, and chiefly affected the thighs, calves and muscles of extraocular movement. The mechanism of the myalgia is unknown. CTC grade 1 phlebitis affected every patient for at least one cycle and was caused by the diluent, PET, which contains polyethylene glycol, ethanol and Tween 80. Most patients experienced a 1 g dl-1 decrease in haemoglobin within 1 h of commencing the infusion which was associated with a decrease in haematocrit. Radiolabelled red cell studies were performed in one patient to investigate the anaemia. The survival of radiolabelled red cells during the week following treatment was the same as that seen in the week before treatment. However, there was a temporary accumulation of radiolabelled red cells in the liver during the first hour of treatment, suggesting that pooling of erythrocytes in the liver might account for the decrease in haematocrit. Total or activated PKC concentrations were measured in the peripheral blood mononuclear cells (PBMCs) of three patients for the first 4 h of treatment and during the last hour of the infusion. This showed that PKC activity was significantly modulated during the infusion. Bryostatin

  3. Advances in endoscopic ultrasound imaging of colorectal diseases.

    PubMed

    Cârțână, Elena Tatiana; Gheonea, Dan Ionuț; Săftoiu, Adrian

    2016-02-01

    malignant subepithelial tumours. Recent reports suggest that EUS elastography enables highly accurate discrimination of colorectal adenocarcinomas from adenomas, while inflammatory bowel disease phenotypes can be distinguished based on the strain ratio calculation. Among EUS-guided therapies, the drainage of abdominal and pelvic collections has been regarded as a safe and effective procedure to be used as an alternative for the transcutaneous route, while the placing of fiducial markers under EUS guidance for targeted radiotherapy in rectal cancer or the use of contrast microbubbles as drug-delivery vehicles represent experimental therapeutic applications that could greatly impact the forthcoming management of patients with colorectal diseases, pending on further investigations. PMID:26855535

  4. [Integrated care for patients with advanced chronic obstructive pulmonary disease].

    PubMed

    Jassem, Ewa; Górecka, Dorota; Krakowiak, Piotr; Kozielski, Jerzy; Słomiński, J Marek; Krajnik, Małgorzata; Fal, Andrzej M

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is the third cause of mortality and disability (assessed by DALY) among patients above 60 year old. Severe and very severe COPD (FEV(1) = equal or less than 50% and 30% of expected value, respectively) is estimated at 20% of all COPD patients. Advanced COPD usually leads to physical and mental deterioration, the patients often manage with the problems caused by the disease and other comorbidities poorly. This leads to increased risk of COPD exacerbations and further deterioration of the patient's status, increased costs of medical care and eventually increased risk of death. Current organization of medical care for those patients does not provide adequate health and social support for them. However, it seems that introducing an integrated approach proposed by World Health Organization, could improve the situation of advanced COPD patients. In Poland, this kind of care has been provided in advanced cancer patients throughout stationary palliative care units and hospices during the last several years. This experience should be helpful in integrating actions of general practitioners and specialized nurses, as well as providing access for the specialists' consultations according to the individual needs of the patients. It should also allow for broad cooperation with auxiliary staff, such as social workers, medical assistants and volunteers, as well as psychologists and clergymen (especially in the terminal phase of the disease).

  5. Non-malignant asbestos diseases in workers in an electrochemical plant.

    PubMed

    Hilt, B

    1987-09-01

    The prevalence of non-malignant asbestos related disorders was studied in a group of men who had been subjected to different levels of asbestos exposure when working at an electrochemical plant producing nitric acid sometime between 1928 and 1970. There were 153 men eligible for an initial clinical examination in 1979-80 and that group has been followed up to 1985. Among the cohort members the "accumulated prevalence" of lung fibrosis alone or in combination with pleural plaques and of "pleural plaques only" was 24.2% and 24.8% respectively. The subgroup with the heaviest exposure had a total prevalence of asbestos related disorders of 82.5%. Only study subjects with lung fibrosis had statistically significant increased prevalences of respiratory symptoms. All subgroups from the study population, however, had mean spirometric values under the age, height, and smoking specific predicted means. Subjects with heavy asbestos exposure and current smoking had a prevalence of three or more respiratory symptoms of 28.8% compared with 5.6% among lightly exposed never smokers. Pleural crepitations at chest auscultation were more prevalent among subjects with radiologically visible asbestos related disorders than among study subjects with normal chest x ray films. During the follow up from 1980 to 1985, three cases of lung cancer, two of pleural malignant mesothelioma, and one of stomach cancer were found among the cohort members.

  6. Midkine: A Novel Biomarker to Predict Malignancy in Patients with Nodular Thyroid Disease.

    PubMed

    Kuzu, Fatih; Arpaci, Dilek; Unal, Mustafa; Altas, Ayfer; Haytaoglu, Gürkan; Can, Murat; Barut, Figen; Kokturk, Furuzan; Ilikhan, Sevil Uygun; Bayraktaroglu, Taner

    2016-01-01

    Background. Midkine (MK), a new heparin-binding growth factor, plays important roles in a variety of biological phenomena such as carcinogenesis, inflammation, and angiogenesis. In this study, we aimed to evaluate serum midkine (SMK) and nodular midkine (NMK) levels in patients with thyroid nodules to predict malignancy and whether there was any association between. Methods. A total of 105 patients (74 women, 31 men) with thyroid nodules were enrolled. The levels of SMK and NMK were measured. Any possible correlation between SMK, NMK, and biochemical, cytopathological, or radiological variables was investigated. Results. Both SMK and NMK were found to be higher in hypoechoic nodules with an irregular border and without a halo (p < 0.05). Serum MK levels were significantly higher in nodules with microcalcifications than nodules with macrocalcification or without calcification (p = 0.001). SMK levels were found to be correlated with NMK levels (SMK 0.63 ng/ml versus 1.04 ng/mL and NMK 0.55 ng/mL versus 0.55 ng/mL, r (2) = 0.54, p < 0.001). Conclusion. Both SMK and NMK can predict tumorigenesis of highly malignant/suspicious thyroid cytopathology and also well correlated with sonographic features of thyroid nodules. We suggest that MK levels may serve as an alternative biomarker, in conjunction with the cytopathological results in preoperative assessment of thyroid nodules. PMID:27446208

  7. Midkine: A Novel Biomarker to Predict Malignancy in Patients with Nodular Thyroid Disease

    PubMed Central

    Kuzu, Fatih; Arpaci, Dilek; Altas, Ayfer; Haytaoglu, Gürkan; Can, Murat; Barut, Figen; Kokturk, Furuzan; Ilikhan, Sevil Uygun; Bayraktaroglu, Taner

    2016-01-01

    Background. Midkine (MK), a new heparin-binding growth factor, plays important roles in a variety of biological phenomena such as carcinogenesis, inflammation, and angiogenesis. In this study, we aimed to evaluate serum midkine (SMK) and nodular midkine (NMK) levels in patients with thyroid nodules to predict malignancy and whether there was any association between. Methods. A total of 105 patients (74 women, 31 men) with thyroid nodules were enrolled. The levels of SMK and NMK were measured. Any possible correlation between SMK, NMK, and biochemical, cytopathological, or radiological variables was investigated. Results. Both SMK and NMK were found to be higher in hypoechoic nodules with an irregular border and without a halo (p < 0.05). Serum MK levels were significantly higher in nodules with microcalcifications than nodules with macrocalcification or without calcification (p = 0.001). SMK levels were found to be correlated with NMK levels (SMK 0.63 ng/ml versus 1.04 ng/mL and NMK 0.55 ng/mL versus 0.55 ng/mL, r2 = 0.54, p < 0.001). Conclusion. Both SMK and NMK can predict tumorigenesis of highly malignant/suspicious thyroid cytopathology and also well correlated with sonographic features of thyroid nodules. We suggest that MK levels may serve as an alternative biomarker, in conjunction with the cytopathological results in preoperative assessment of thyroid nodules. PMID:27446208

  8. Fine Needle Aspiration in the Diagnosis of Childhood Malignant Disease in Uganda

    PubMed Central

    Magrath, I. T.

    1973-01-01

    One hundred aspirations using a fine needle have been performed on 94 patients with a suspected diagnosis of malignant tumour, 31 of which were in patients with recurrent tumour. In 90 aspirates where histology was also available there was agreement between histological and cytological diagnosis in 81 (90%). This percentage was identical when only previously undiagnosed tumours were considered (60). In 4 aspirates no cells were obtained from tumours in which a diagnosis was made histologically and in 5 there was disagreement with histology, either regarding the presence of malignancy, or tumour type. The technique of fine needle aspiration is simple, rapid, safe and reliable. It is particularly valuable when emergency treatment is required, necessitating a very rapid diagnosis, or when the tumour is entirely intra-abdominal and the patient is unfit for laparotomy. Repeat aspirates may be performed to assess progress following treatment, or multiple suspected tumour sites may be aspirated to assist staging. The technique may be used to confirm the presence of relapsing tumour. Aspiration cytology may prove valuable as a further dimension in the interpretation of histological sections in a variety of childhood tumours, and in some circumstances may be sufficient in itself to establish a diagnosis. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8 PMID:4131498

  9. Advances in Diagnosis and Management of Celiac Disease

    PubMed Central

    Kelly, Ciarán P.; Bai, Julio C.; Liu, Edwin; Leffler, Daniel A.

    2015-01-01

    Celiac disease is an autoimmune disorder induced by dietary gluten in genetically predisposed individuals. It has a prevalence of ∼1% in many populations worldwide. New diagnoses have increased substantially, due to increased awareness, better diagnostic tools, and probable, real increases in incidence. The breadth of recognized clinical presentations continues to expand, making the disorder highly relevant to all physicians. Newer diagnostic tools, including serologic tests for antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptide, greatly facilitate diagnosis. Tests for celiac-permissive HLA DQ2 and DQ8 molecules are useful in defined clinical situations. Celiac disease is diagnosed by histopathologic examination of duodenal biopsies. However, according to recent controversial guidelines, a diagnosis can be made without biopsy in certain circumstances, especially for children. Symptoms, mortality, and risk for malignancy can each be reduced by adherence to a gluten-free diet. This treatment is a challenge, however, as the diet is expensive, socially isolating, and not always effective in controlling symptoms or intestinal damage. Hence, there is increasing interest in developing non-dietary therapies. PMID:25662623

  10. Encephalopathy is the dose-limiting toxicity of intravenous hepsulfam: results of a phase I trial in patients with advanced hematological malignancies.

    PubMed

    Larson, R A; Geller, R B; Janisch, L; Milton, J; Grochow, L B; Ratain, M J

    1995-01-01

    Hepsulfam is a bisulfamic ester which is similar in structure to busulfan and is believed to act as a bifunctional alkylator inducing both DNA-DNA and DNA-protein crosslinks. Prior studies in patients with refractory solid tumors have identified the dose-limiting toxicity of hepsulfam to be cumulative myelosuppression resulting in prolonged leukopenia and thrombocytopenia. This phase I trial was designed to determine the maximally tolerated dose of hepsulfam administered intravenously in patients with refractory leukemias and other advanced hematologic malignancies. Hepsulfam was administered as a 30-min or 2-h intravenous infusion to 21 patients with advanced leukemia or multiple myeloma. All patients had been extensively treated and had progressive disease. Cycles were repeated every 5 weeks. Cohorts of patients were treated at 360, 480, 640, and 800 mg/m2. The dose-limiting toxicity of intravenous hepsulfam was severe encephalopathy. The single patient treated at 800 mg/m2 became comatose within 48 h and required 3 weeks for his mental status to return to baseline. There were, however, no irreversible neurological sequelae. Several patients treated at 640 mg/m2 had clinical evidence of toxic deliriums and slowing of alpha rhythm waves on electroencephalograms indicative of a gray-matter encephalopathy. When hepsulfam was infused over 30 min, patients complained of uncomfortable parasthesias, but when the drug was administered over 2 h, these acute symptoms were less common. Myelosuppression was observed in most patients. Among those patients who had some suppression of their leukemia, peripheral blood counts recovered to pretreatment levels after 3-5 weeks. Apart from CNS toxicity, non-hematologic toxicity was minimal. Pharmacokinetic studies demonstrated rapid clearance of hepsulfam so that the drug was not reliably detected in the plasma after 24 h. The recommended phase II dose of hepsulfam as a single 2-h intravenous infusion is 480 mg/m2, but this dose

  11. Malignant giant pheochromocytoma: a case report and review of the literature

    PubMed Central

    Arcos, Cristina Torres; Luque, Virgilio Ruiz; Luque, José Aguilar; García, Pablo Martínez; Jiménez, Antonia Brox; Muñoz, Macarena Márquez

    2009-01-01

    Malignant pheochromocytoma is a rare disease and surgical resection is the only curative treatment. There are no definitive histological or cytological criteria of malignancy, as it is impossible to determine this condition in the absence of advanced locoregional disease or metastases. We report a case of a patient with a giant retroperitoneal tumour, the second largest to be published, which was diagnosed as a malignant pheochromocytoma; it was treated with surgery. The literature is reviewed to evaluate tumour features and criteria to distinguish between benign and malignant pheochromocytomas. PMID:20019963

  12. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported.

  13. Advances and highlights in mechanisms of allergic disease in 2015.

    PubMed

    Wawrzyniak, Paulina; Akdis, Cezmi A; Finkelman, Fred D; Rothenberg, Marc E

    2016-06-01

    This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported. PMID:27090934

  14. The intra-bone marrow injection of cord blood cells extends the possibility of transplantation to the majority of patients with malignant hematopoietic diseases.

    PubMed

    Frassoni, Francesco; Varaldo, Riccardo; Gualandi, Francesca; Bacigalupo, Andrea; Sambuceti, GianMario; Sacchi, Nicoletta; Podestà, Marina

    2010-06-01

    Cord blood transplant (CBT) in adult patients is scarcely utilized because of the risk of graft failure or very delayed platelet recovery. To improve the capacity and the speed to engraft, we have developed an intra-bone (IB) cord blood transplant technique. 75 patients with hematological malignancies, categorized by disease phase as early (18%), intermediate (20%) and advanced (62%), were transplanted. The median cell dose (TNC) infused was: 2.6 (1.35-5.4)×10(7)/kg; the HLA disparity was: 12 cases=5/6, 62 cases=4/6 and 1 case=3/6 matched antigens. 72/75 patients engrafted (96%); median day of recovery of neutrophils (PMN) >500×10(9)/L and platelets (PLT) >20 000×10(9)/L was: 23 (14-44) and 35 (16-70) days respectively. The outcomes at 2 years according to Kaplan-Meier are: OS=46%±5; RI=18%±2; NRM=39%±5. Acute GVHD incidence/severity was: grade 0-I=64%, II=14%, III-IV=0%. The incidence of Chronic GVHD was globally low but in 3 cases was very severe. Intra-bone CBT is associated with high rate of engraftment, early and robust platelet recovery, low incidence of acute GVHD. A very promising aspect is that the relapse rate is low considering the advanced phase of the disease in two/thirds of patients. A suitable CBU was found for nearly every patient searching for a CBU. Therefore, IB CBT extends the possibility to transplant any patient for whom this approach represents the sole possibility of long-term survival.

  15. [Advances in prenatal diagnosis of congenital heart diseases].

    PubMed

    Muner-Hernando, Marta; Gil-Mira, Mar; Zapardiel, Ignacio

    2013-06-01

    Congenital heart diseases are the most frequent abnormalities at the time of delivery. Their importance lays in the fact that they represent 46% of neonatal deaths and they are cause of a high morbidity rate. However, an early diagnosis is difficult. The aim of this revision is to give an update on the advances in the prenatal diagnosis of congenital heart diseases and their advantages compared to conventional sonography. The introduction of new technology in the detection of congenital heart diseases has improved the acquisition of better images in terms of resolution and quality. However, there is a lack of large studies to prove its benefits in non-selected population, although preliminary studies seem to give faithful results.

  16. Advances in epigenetics and epigenomics for neurodegenerative diseases.

    PubMed

    Qureshi, Irfan A; Mehler, Mark F

    2011-10-01

    In the post-genomic era, epigenetic factors-literally those that are "over" or "above" genetic ones and responsible for controlling the expression and function of genes-have emerged as important mediators of development and aging; gene-gene and gene-environmental interactions; and the pathophysiology of complex disease states. Here, we provide a brief overview of the major epigenetic mechanisms (ie, DNA methylation, histone modifications and chromatin remodeling, and non-coding RNA regulation). We highlight the nearly ubiquitous profiles of epigenetic dysregulation that have been found in Alzheimer's and other neurodegenerative diseases. We also review innovative methods and technologies that enable the characterization of individual epigenetic modifications and more widespread epigenomic states at high resolution. We conclude that, together with complementary genetic, genomic, and related approaches, interrogating epigenetic and epigenomic profiles in neurodegenerative diseases represent important and increasingly practical strategies for advancing our understanding of and the diagnosis and treatment of these disorders.

  17. Tetanus immunity in patients with hematological malignancies.

    PubMed

    Hamarström, V; Pauksen, K; Svensson, H; Oberg, G; Paul, C; Ljungman, P

    1998-09-01

    The aim of this study was to investigate long-term immunity to tetanus toxoid among patients with hematological disease who had been treated with conventional doses of chemotherapy. Altogether 206 patients with different hematological malignancies were included in the study. There were marked differences between the rates of seronegativity against tetanus, varying from 20% to 70% in different groups of study patients. We found that 21 of 80 (36%) patients with AML, 45 of 80 (56%) with ALL, 12 of 22 (54%) with lymphoma, 4 of 13 (31%) with myeloma and 2 of 11 (18%) with CML were not immune to tetanus. In a multivariate logistic regression model increasing age (P = 0.0001), lymphoid malignancy (P = 0.0005) and advanced disease stage (P = 0.0001) were independent risk factors for loss of tetanus immunity in patients with hematological malignancies.

  18. Elastic Deformation Properties of Implanted Endobronchial Wire Stents in Benign and Malignant Bronchial Disease: A Radiographic In Vivo Evaluation

    SciTech Connect

    Hautmann, Hubert; Rieger, Johannes; Huber, Rudolf M.; Pfeifer, Klaus J.

    1999-03-15

    Purpose: To evaluate the long-term mechanical behavior in vivo of expandable endobronchial wire stents, we imaged three different prostheses in the treatment of tracheobronchial disease. Methods: Six patients with bronchial stenoses (three benign, three malignant) underwent insertion of metallic stents. Two self-expandable Wallstents, two balloon-expandable tantalum Strecker stents and two self-expandable nitinol Accuflex stents were used. Measurements of deformation properties were performed during voluntary cough by means of fluoroscopy, at 1 month and 7-10 months after implantation. The procedures were videotaped, their images digitized and the narrowing of stent diameters calculated at intervals of 20 msec. Results: After stent implantation all patients improved with respect to ventilatory function. Radial stent narrowing during cough reached 53% (Wallstent), 59% (tantalum Strecker stent), and 52% (nitinol Accuflex stent) of the relaxed post-implantation diameter. Stent compression was more marked in benign compared with malignant stenoses. In the long term permanent deformation occurred with the tantalum Strecker stents; the other stents were unchanged. Conclusion: Endobronchial wire stents can be helpful in the treatment of major airway collapse and obstructing bronchial lesions. However, evidence of material fatigue as a possible effect of exposure to recurrent mechanical stress on the flexible mesh tube may limit their long-term use. This seems to be predominantly important in benign bronchial collapse.

  19. Phase I and pharmacokinetic study of docetaxel combined with melphalan and carboplatin, with autologous hematopoietic progenitor cell support, in patients with advanced refractory malignancies.

    PubMed

    Nieto, Yago; Shpall, Elizabeth J; Bearman, Scott I; McSweeney, Peter A; Cagnoni, Pablo J; Matthes, Steve; Gustafson, Dan; Long, Michael; Barón, Anna E; Jones, Roy B

    2005-04-01

    The purpose of this study was to define the maximal tolerated dose (MTD), extramedullary toxicities, and pharmacokinetics of docetaxel combined with high-dose melphalan and carboplatin with autologous hematopoietic progenitor cell support. Fifty-nine patients with advanced refractory malignancy (32 breast cancer, 10 non-Hodgkin lymphoma, 6 germ cell tumors, 4 Hodgkin disease, 4 ovarian cancer, 2 sarcoma, and 1 unknown primary adenocarcinoma) with a median of 3 prior chemotherapy regimens and a median of 3 organs involved were enrolled. Treatment included docetaxel (150-550 mg/m2 infused over 2 hours on day -6), melphalan (150-165 mg/m2 infused over 15 minutes from day -5 to -3), and carboplatin (1000-1300 mg/m2 as a 72-hour continuous infusion from day -5). Five patients died from direct regimen-related organ toxicity (2 capillary leak syndrome, 2 enterocolitis, and 1 hepatic toxicity), and 1 additional patient died from pulmonary aspergillosis. The docetaxel MTD was defined as 400 mg/m 2 , combined with melphalan (150 mg/m2 ) and carboplatin (1000 mg/m2 ). The MTD cohort was expanded to enroll a total of 26 patients, 1 of whom died from toxic enterocolitis. The remaining 25 patients presented the following extramedullary toxicity profile, which was manageable and largely reversible: stomatitis, myoarthralgias, peripheral neuropathy, gastrointestinal and cutaneous toxicities, and syndrome of inappropriate antidiuretic hormone secretion. Docetaxel exhibited linear pharmacokinetics in the dose range tested (150-550 mg/m2 ). Pharmacodynamic correlations were noted between the docetaxel area under the curve and peripheral neuropathy or stomatitis. The response rate among 38 patients with measurable disease was 95%, with 47% complete responses. At a median follow-up of 26 months (range, 7-72 months), the 3-year event-free survival and overall survival were 26% and 36%, respectively. In conclusion, a 4-fold dose escalation of docetaxel, combined with melphalan and

  20. Congenital heart disease in Mexico: advances of the regionalization project.

    PubMed

    Calderón-Colmenero, Juan; Cervantes-Salazar, Jorge; Curi-Curi, Pedro; Ramírez-Marroquín, Samuel

    2013-04-01

    Consistent with the mission of the World Society for Pediatric and Congenital Heart Surgery to promote health care for children with congenital heart disease all around the world, a Mexican Association of Specialists in Congenital Heart Disease (abbreviated in Spanish as AMECC) was created in Mexico in 2008. Our efforts were coordinated with those of the National Health Secretary with the objective being implementation of a national plan for regionalization of care for patients with congenital heart disease. To improve our knowledge related to technologic and human resources for management of congenital heart disease, we developed a national survey. Finally, a national database was created for collecting all Mexican centers' information related to congenital heart disease care in order to quantify the advances related to the proposed plans. The database utilized international consensus nomenclature. The aim of this article is to show the sequence of our actions in relation to direct accomplishments and the current status of congenital heart disease care in Mexico. This article emphasizes the main aspects of these actions: regionalization project implementation, national survey results, and cardiovascular pediatric surgical database creation. Knowledge of outcomes related to successful actions would be useful for those countries that face similar challenges and may lead them to consider adoption of similar measures with the respective adjustments to their own reality.

  1. An overview of advance care planning for patients with advanced chronic kidney disease: The basics.

    PubMed

    Wasylynuk, Betty Ann; Davison, Sara N

    2016-01-01

    As the number of Canadians living with end-stage kidney disease (ESKD) continues to grow, even higher numbers are living with advanced chronic kidney disease (CKD). Many of these people will eventually require renal replacement therapy (RRT), either dialysis or transplantation. More than 50% of patients starting RRT today are aged 65 or older, with the fastest growing group being patients 75 years and older. Despite advances to dialysis technology and dialysis care, the mortality rates remain high and dialysis patients' end-of-life care may not align with their preferences or values. Advance care planning (ACP) is an essential component of quality comprehensive kidney care. Kidney care teams develop strong relationships with their patients and are well positioned to integrate ACP into routine kidney care. This article defines ACP, outlines the essential components of ACP, and discusses the benefits, challenges, and special considerations of ACP. By enhancing the kidney care team's understanding of ACP, this article aims to assist in integrating ACP into routine kidney care for patients with advanced CKD. PMID:27215058

  2. Atherogenicity and carcinogenicity of high-arsenic artesian well water. Multiple risk factors and related malignant neoplasms of blackfoot disease.

    PubMed

    Chen, C J; Wu, M M; Lee, S S; Wang, J D; Cheng, S H; Wu, H Y

    1988-01-01

    The objective of this study was to examine multiple risk factors and correlated malignant neoplasms of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous exposure to high-arsenic artesian well water. A total of 241 BFD cases, including 169 with spontaneous or surgical amputations of affected extremities, and 759 age-sex-residence-matched healthy community controls were studied to explore the risk factors of BFD. Multiple logistic regression analysis showed that artesian well water consumption, arsenic poisoning, familial history of BFD, and undernourishment were significantly associated with the development of BFD. The life-table method used to analyze cancer mortality of 789 BFD patients followed for 15 years showed a significantly higher mortality from cardiovascular diseases, peripheral vascular diseases, and cancers of bladder, skin, lung, and liver among BFD patients as compared with the general population in Taiwan or residents in the BFD-endemic area. The results imply the atherogenicity and carcinogenicity of the artesian well water in the BFD-endemic area.

  3. Atherogenicity and carcinogenicity of high-arsenic artesian well water. Multiple risk factors and related malignant neoplasms of blackfoot disease

    SciTech Connect

    Chen, C.J.; Wu, M.M.; Lee, S.S.; Wang, J.D.; Cheng, S.H.; Wu, H.Y.

    1988-09-01

    The objective of this study was to examine multiple risk factors and correlated malignant neoplasms of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous exposure to high-arsenic artesian well water. A total of 241 BFD cases, including 169 with spontaneous or surgical amputations of affected extremities, and 759 age-sex-residence-matched healthy community controls were studied to explore the risk factors of BFD. Multiple logistic regression analysis showed that artesian well water consumption, arsenic poisoning, familial history of BFD, and undernourishment were significantly associated with the development of BFD. The life-table method used to analyze cancer mortality of 789 BFD patients followed for 15 years showed a significantly higher mortality from cardiovascular diseases, peripheral vascular diseases, and cancers of bladder, skin, lung, and liver among BFD patients as compared with the general population in Taiwan or residents in the BFD-endemic area. The results imply the atherogenicity and carcinogenicity of the artesian well water in the BFD-endemic area.

  4. Palliative care for patients with advance chronic kidney disease.

    PubMed

    Douglas, C A

    2014-01-01

    Over the past three decades there has been a dramatic rise in the number of patients with advanced chronic kidney disease. The fastest expanding group receiving dialysis has been the elderly. However, for those patients who are very elderly with co-morbidity, dialysis may not offer a survival advantage. Therefore, active conservative management is a growing service offered by many renal units in the UK and focuses on non-dialytic correction of fluid and electrolyes, management of renal anaemia, and assessment and management of symptoms. The five-year survival of a patient over 75 years of age starting dialysis is 20% and if a patient is over 75 years, has co-morbidity, or a poor performance status, dialysis may not offer any survival advantage. Whether a patient is managed by dialysis or by conservative management the symptom burden suffered is high. These symptoms are under-recognised and often managed poorly because of increased drug toxicity in renal failure. This complex group of patients require close working between renal, palliative care, medicine for the elderly, and community teams, to allow best quality of life and end of life care. This review describes some of the challenges in providing Advanced Care Planning for dialysis and conservatively managed patients, highlights the symptom burden of patients with advanced chronic kidney disease, and offers guidance in how to manage the symptoms effectively.

  5. Recommendations for Risk Categorization and Prophylaxis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Expert Opinion (TEO-4)

    PubMed Central

    Boğa, Can; Bolaman, Zahit; Çağırgan, Seçkin; Karadoğan, İhsan; Özcan, Mehmet Ali; Özkalemkaş, Fahir; Saba, Rabin; Sönmez, Mehmet; Şenol, Esin; Akan, Hamdi; Akova, Murat

    2015-01-01

    This is the last of a series of articles on invasive fungal infections prepared by opinion leaders in Turkey. The aim of these articles is to guide clinicians in managing invasive fungal diseases in hematological malignancies and stem cell transplantation based on the available best evidence in this field. The previous articles summarized the diagnosis and treatment of invasive fungal disease and this article aims to explain the risk categorization and guide the antifungal prophylaxis in invasive fungal disease. PMID:26316478

  6. Extra-intestinal malignancies in inflammatory bowel diseases: An update with emphasis on MDCT and MR imaging features.

    PubMed

    Dohan, A; Faraoun, S A; Barral, M; Guerrache, Y; Boudiaf, M; Dray, X; Hoeffel, C; Allez, M; Farges, O; Beaugerie, L; Aparicio, T; Marteau, P; Fishman, E K; Lucidarme, O; Eveno, C; Pocard, M; Dautry, R; Soyer, P

    2015-09-01

    Inflammatory bowel diseases (IBD) are associated with an increased risk of gastrointestinal cancers and more specifically in sites affected by chronic inflammation. However, patients with IBD have also an increased risk for developing a variety of extra-intestinal cancers. In this regard, hepatobiliary cancers, such as cholangiocarcinoma, are more frequently observed in IBD patients because of a high prevalence of primary sclerosing cholangitis, which is considered as a favoring condition. Extra-intestinal lymphomas, mostly non-Hodgkin lymphomas, and skin cancers are also observed with an increased incidence in IBD patients by comparison with that in patients without IBD. This review provides an update on demographics, risk factors and clinical features of extra-intestinal malignancies, including cholangiocarcinoma, hepatocellular carcinoma and lymphoma, that occur in patients with IBD along with a special emphasis on the multidetector row computed tomography and magnetic resonance imaging features of these uncommon conditions. PMID:25846686

  7. Diagnosis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Turkish Expert Opinion (TEO-2)

    PubMed Central

    Arıkan Akdağlı, Sevtap; Azap, Alpay; Başaran Demirkazık, Figen; Ener, Beyza; Aşcıoğlu Hayran, Sibel; Özdemir Kumbasar, Özlem; Metan, Gökhan; Odabaşı, Zekaver; Uzun, Ömrüm; Akan, Hamdi

    2014-01-01

    One of the most problematic issues in hematological malignancies is the diagnosis of invasive fungal diseases. Especially, the difficulty of mycological diagnosis and the necessity of immediate intervention in molds have led to the adoption of “surrogate markers” that do not verify but rather strongly suggest fungal infection. The markers commonly used are galactomannan (GM), beta-glucan, and imaging methods. Although there are numerous studies on these diagnostic approaches, none of these markers serve as a support for the clinician, as is the case in human immunodeficiency virus (HIV) or cytomegalovirus (CMV) infections. This paper has been prepared to explain the diagnostic tests. As molecular tests have not been standardized and are not used routinely in the clinics, they will not be mentioned here. PMID:25541650

  8. Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis

    PubMed Central

    Lo, Sarah M.; Choi, Murim; Liu, Jun; Jain, Dhanpat; Boot, Rolf G.; Kallemeijn, Wouter W.; Aerts, Johannes M. F. G.; Pashankar, Farzana; Kupfer, Gary M.; Mane, Shrikant; Lifton, Richard P.

    2012-01-01

    Gaucher disease (GD), an inherited macrophage glycosphingolipidosis, manifests with an extraordinary variety of phenotypes that show imperfect correlation with mutations in the GBA gene. In addition to the classic manifestations, patients suffer from increased susceptibility to hematologic and nonhematologic malignancies. The mechanism(s) underlying malignancy in GD is not known, but is postulated to be secondary to macrophage dysfunction and immune dysregulation arising from lysosomal accumulation of glucocerebroside. However, there is weak correlation between GD/cancer phenotype and the systemic burden of glucocerebroside-laden macrophages. Therefore, we hypothesized that genetic modifier(s) may underlie the GD/cancer phenotype. In the present study, the genetic basis of GD/T-cell acute lymphoblastic lymphoma in 2 affected siblings was deciphered through genomic analysis. GBA gene sequencing revealed homozygosity for a novel mutation, D137N. Whole-exome capture and massively parallel sequencing combined with homozygosity mapping identified a homozygous novel mutation in the MSH6 gene that leads to constitutional mismatch repair deficiency syndrome and increased cancer risk. Enzyme studies demonstrated that the D137N mutation in GBA is a pathogenic mutation, and immunohistochemistry confirmed the absence of the MSH6 protein. Therefore, precise phenotype annotation followed by individual genome analysis has the potential to identify genetic modifiers of GD, facilitate personalized management, and provide novel insights into disease pathophysiology. PMID:22493294

  9. [Thoracoscopic management of suspected thoraco-pulmonary malignant diseases in pediatric age].

    PubMed

    Lima, M; Bertozzi, M; Dòmini, M; Pession, A; Ruggeri, G; Libri, M; Antonellini, C; Pelusi, G; Messina, P; Fae, M

    2004-01-01

    Recent improvements and miniaturization of instruments have encouraged a wider use of thoracoscopy and laparoscopy as a modality for diagnostic and operative procedures in pediatric age. The utility of thoracoscopy in pediatric patients with suspected thoracopulmonary oncological diseases is shown by diagnostic accuracy and, if necessary, the possibility to perform at the meantime a mininvasive surgery. We report the experience of our Institution in 16 patients with suspected thoraco-pulmonary oncological diseases and treated for this reason with thoracoscopy. Thoracoscopic is indicated in cases of suspected oncological diseases in children both for diagnosis and treatment.

  10. Malignant Catarrhal Fever: An Emerging Disease in the African Buffalo (Syncerus caffer).

    PubMed

    Pfitzer, S; Last, R; Espie, I; van Vuuren, M

    2015-06-01

    Within the tribe Bovini in the subfamily Bovinae, the water buffalo (Bubalus Bubalis), American bison (Bison bison), European bison (Bubalus bonasus) and yak (Bos grunniens) are recognized as species highly susceptible to malignant catarrhal fever (MCF). In contrast, the lack of reports describing clinical MCF in the African buffalo (Syncerus caffer) whether free ranging or captive has led to a perception that African buffaloes are resistant to MCF. During the last decade, several cases of MCF in African buffaloes were confirmed in South Africa and experience with seven of these cases is described in this report. Detection of viral nucleic acid in blood or tissues was successful in six African buffaloes that suffered from clinical signs compatible with MCF. Four were positive for infection with ovine herpesvirus type 2 (the causative virus of sheep-associated MCF), and two were positive for alcelaphine herpesvirus type 1 (causative virus of wildebeest-associated MCF). Histopathological examination of tissue samples from all the animals yielded typical lesions that were consistent with those described for MCF in domestic cattle. Developments in the management of African buffaloes translocated from their traditional habitats have likely contributed to the identification of another susceptible host in the subfamily Bovinae.

  11. Advances in nanotechnology for the management of coronary artery disease.

    PubMed

    Rhee, June-Wha; Wu, Joseph C

    2013-02-01

    Nanotechnology holds tremendous potential to advance the current treatment of coronary artery disease. Nanotechnology may assist medical therapies by providing a safe and efficacious delivery platform for a variety of drugs aimed at modulating lipid disorders, decreasing inflammation and angiogenesis within atherosclerotic plaques, and preventing plaque thrombosis. Nanotechnology may improve coronary stent applications by promoting endothelial recovery on a stent surface utilizing bio-mimetic nanofibrous scaffolds, and also by preventing in-stent restenosis using nanoparticle-based delivery of drugs that are decoupled from stents. Additionally, nanotechnology may enhance tissue-engineered graft materials for application in coronary artery bypass grafting by facilitating cellular infiltration and remodeling of a graft matrix.

  12. Intraindividual Variability of Nonmotor Fluctuations in Advanced Parkinson's Disease.

    PubMed

    Fauser, Mareike; Löhle, Matthias; Ebersbach, Georg; Odin, Per; Fuchs, Gerd; Jost, Wolfgang H; Chaudhuri, K Ray; Koch, Rainer; Storch, Alexander

    2015-01-01

    Nonmotor symptoms (NMS) fluctuate in conjunction with motor oscillations in advanced Parkinson's disease (PD), though little is known about the variability of NMS fluctuations in individual patients. We aimed to assess within-patient variability in frequency and severity of NMS during a series of five patient-perceived motor On and Off periods in 38 fluctuating PD patients from the multicenter NonMotorFluctuations in PD study using a visual analogue scale. NMS frequency and severity appeared moderately variable in both motor states within individual patients. Symptom severity ranges between motor states showed high variability and were larger in motor Off states for most NMS. PMID:26639660

  13. [Advances in the researches of lutein and alzheimer's disease].

    PubMed

    Xu, Xianrong; Lin, Xiaoming

    2015-05-01

    Lutein, a kind of oxycarotenoid, can pass the blood brain barrier and preferentially accumulate in the human brain, which is the most abundant carotenoid in human brain. Evidence from multiple studies suggested that lutein was closely related to age-related cognitive decline and risk of Alzheimer's disease (AD) in human. Dietary, plasma and brain concentrations of lutein were negatively associated with age-related cognitive decline. Lutein concentrations in plasma and brain were significantly lower in AD patients than those of health control. In human brain, lutein was the sole carotenoid which consistently associated with a range of cognitive function measures. In elderly women, lutein supplement can improve the cognitive function. In this article, we systematically reviewed the literature on the role of lutein in age-related cognitive decline and alzheimer's disease and its possible mechanisms. It may prove some benefit information for the advanced research and prevention of AD.

  14. Individualized strategies to target specific mechanisms of disease in malignant melanoma patients displaying unique mutational signatures

    PubMed Central

    Vidal, Rebeca; Pisonero, Helena; Varela, Ignacio; León-Castillo, Alicia; Trillo, Eugenio; González-Vela, Carmen; García-Diaz, Nuria; Almaraz, Carmen; Moreno, Thaidy; Cereceda, Laura; Madureira, Rebeca; Martinez, Nerea; Ortiz-Romero, Pablo; Valdizán, Elsa; Piris, Miguel; Vaqué, José

    2015-01-01

    Targeted treatment of advanced melanoma could benefit from the precise molecular characterization of melanoma samples. Using a melanoma-specific selection of 217 genes, we performed targeted deep sequencing of a series of biopsies, from advanced melanoma cases, with a Breslow index of ≥4 mm, and/or with a loco-regional infiltration in lymph nodes or presenting distant metastasis, as well of a collection of human cell lines. This approach detected 3–4 mutations per case, constituting unique mutational signatures associated with specific inhibitor sensitivity. Functionally, case-specific combinations of inhibitors that simultaneously targeted MAPK-dependent and MAPK-independent mechanisms were most effective at inhibiting melanoma growth, against each specific mutational background. These observations were challenged by characterizing a freshly resected biopsy from a metastatic lesion located in the skin and soft tissue and by testing its associated therapy ex vivo and in vivo using melanocytes and patient-derived xenografted mice, respectively. The results show that upon mutational characterization of advanced melanoma patients, specific mutational profiles can be used for selecting drugs that simultaneously target several deregulated genes/pathways involved in tumor generation or progression. PMID:26327537

  15. Ionizing radiation promotes advanced malignant traits in nasopharyngeal carcinoma via activation of epithelial-mesenchymal transition and the cancer stem cell phenotype

    PubMed Central

    SU, ZHONGWU; LI, GUO; LIU, CHAO; REN, SHULING; TIAN, YONGQUAN; LIU, YONG; QIU, YUANZHENG

    2016-01-01

    Post-irradiation residual mass and recurrence always suggest a worse prognosis for nasopharyngeal carcinoma (NPC). Our study aimed to investigate the malignant behaviors of post-irradiation residual NPC cells, to identify the potential underlying mechanisms and to search for appropriate bio-targets to overcome this malignancy. Two NPC cell lines were firstly exposed to 60 Gy irradiation, and residual cells were collected. In our previous study, colony formation assay detected the radioresistance of these cells. Here, the CCK-8 assay examined the cell sensitivity to paclitaxel and cisplatin. Wound-healing and Transwell assays were performed to investigate cell motility and invasion capabilities. Inverted phase-contrast microscopy was used to observe and photograph the morphology of cells. Expression levels of epithelial-mesenchymal transition (EMT)-related proteins were detected by western blot assay in NPC cells and tissues. The mRNA levels of cancer stem cell (CSC)-related genes were detected via qRT-PCR. The results revealed that residual NPC cells exhibited enhanced radioresistance and cross-resistance to paclitaxel and cisplatin. Higher capacities of invasion and migration were also observed. An elongated morphology with pseudopodia formation and broadening in the intercellular space was observed in the residual cells. Downregulation of E-cadherin and upregulation of vimentin were detected in the residual NPC cells and tissues. CSC-related Lgr5 and c-myc were significantly upregulated in the CNE-2-Rs and 6-10B-Rs radioresistance cells. Higher proportions of Lgr5+ cells were observed in radioresistant cells via immunofluorescent staining and flow cytometry. In conclusion, our study demonstrated that residual NPC cells had an advanced malignant transition and presented with both EMT and a CSC phenotype. This provides a possible clue and treatment strategy for advanced and residual NPC. PMID:27108809

  16. Recent Advances in the Genetics of Autoimmune Disease

    PubMed Central

    Gregersen, Peter K.; Olsson, Lina M.

    2010-01-01

    Extraordinary technical advances in the field of human genetics over the past few years have catalyzed an explosion of new information about the genetics of human autoimmunity. In particular, the ability to scan the entire genome for common polymorphisms that associate with disease has led to the identification of numerous new risk genes involved in autoimmune phenotypes. Several themes are emerging. Autoimmune disorders have a complex genetic basis; multiple genes contribute to disease risk, each with generally modest effects independently. In addition, it is now clear that common genes underlie multiple autoimmune disorders. There is also heterogeneity among subphenotypes within a disease and across major racial groups. The current crop of genetic associations are only the start of a complete catalog of genetic factors for autoimmunity, and it remains unclear to what extent common variation versus multiple rare variants contribute to disease susceptibility. The current review focuses on recent discoveries within functionally related groups of genes that provide clues to novel pathways of pathogenesis for human autoimmunity. PMID:19302045

  17. Methodological advances in drug discovery for Chagas disease

    PubMed Central

    Bustamante, Juan M.; Tarleton, Rick L.

    2011-01-01

    Introduction Chagas disease is the highest impact human infectious disease in Latin America, and the leading worldwide cause of myocarditis. Despite the availability of several compounds that have demonstrated efficacy in limiting the effects of T. cruzi, these compounds are rarely used due to their variable efficacy, substantial side effects and the lack of methodologies for confirming their effectiveness. Furthermore, the development of more efficacious compounds is challenged by limitations of systems for assessing drug efficacy in vitro and in vivo. Areas covered Herein, the authors review the development of Chagas disease drug discovery methodology, focusing on recent developments in high throughput screening, in vivo testing methods and assessments of efficacy in humans. Particularly, this review documents the significant progress that has taken place over the last 5 years that have paved the way for both target-focused and high-throughput screens of compound libraries. Expert opinion The tools for in vitro and in vivo screening of anti-T. cruzi compounds have improved dramatically in the last few years and there are now a number of excellent in vivo testing models available; this somewhat alleviates the bottleneck issue of quickly and definitively demonstrating in vivo efficacy in a relevant host animal system. These advances emphasize the potential for additional progress resulting in new treatments for Chagas disease in the coming years. That being said, national and international agencies must improve the coordination of research and development efforts in addition to cultivating the funding sources for the development of these new treatments. PMID:21712965

  18. Impaired phospholipid-related signal transduction in advanced Huntington's disease.

    PubMed

    Puri, B K

    2001-09-01

    The aim of this study was to test the hypothesis that Huntington's disease is associated with impaired phospholipid-related signal transduction using the niacin skin flush test. This is the first reported use of this test in this patient group. The response to topical aqueous methyl nicotinate solution was recorded at 5 min intervals over 20 min in six in-patients with advanced (stage III) Huntington's disease and in 14 age- and sex-matched normal individuals with no history of this or any other major neurological disorder. The volumetric niacin response (VNR) (mean +/- S.E.M.) in the patients with Huntington's disease, 16.3 +/- 2.6 mol x s x l(-1), was significantly lower than the mean VNR of 28.3 +/- 2.1 mol x s x l(-1) in the control group (P = 0.004). These results are consistent with the conclusion that Huntington's disease may be associated with an abnormality of neuronal membrane fatty acid metabolism, possibly as a consequence of an as yet unidentified action of huntingtin.

  19. Febuxostat for hyperuricemia in patients with advanced chronic kidney disease.

    PubMed

    Akimoto, Tetsu; Morishita, Yoshiyuki; Ito, Chiharu; Iimura, Osamu; Tsunematsu, Sadao; Watanabe, Yuko; Kusano, Eiji; Nagata, Daisuke

    2014-01-01

    Febuxostat is a nonpurine xanthine oxidase (XO) inhibitor, which recently received marketing approval. However, information regarding the experience with this agent among advanced chronic kidney disease (CKD) patients is limited. In the current study, we investigated the effects of oral febuxostat in patients with advanced CKD with asymptomatic hyperuricemia. We demonstrated, for the first time, that not only the serum levels of uric acid (UA) but also those of 8-hydroxydeoxyguanosine, an oxidative stress marker, were significantly reduced after six months of febuxostat treatment, with no adverse events. These results encouraged us to pursue further investigations regarding the clinical impact of lowering the serum UA levels with febuxostat in advanced CKD patients in terms of concomitantly reducing oxidative stress via the blockade of XO. More detailed studies with a larger number of subjects and assessments of the effects of multiple factors affecting hyperuricemia, such as age, sex, and dietary habits, would shed light on the therapeutic challenges of treating asymptomatic hyperuricemia in patients with various stages of CKD. PMID:25210423

  20. Necrotising herpetic retinopathy in patients with advance HIV disease.

    PubMed Central

    Miller, R F; Brink, N S; Cartledge, J; Sharvell, Y; Frith, P

    1997-01-01

    OBJECTIVES: To describe the presenting features, clinical and laboratory diagnosis, response to treatment, and outcome of necrotising herpetic retinopathy (NHR) in HIV infected patients. METHODS: Retrospective case records/laboratory data review of five HIV infected patients presenting to the specialist HIV/AIDS unit at UCL Hospitals, London from April 1994 to August 1996 with a clinical diagnosis of NHR. RESULTS: All patients had advanced HIV disease with a median CD4 count of 20.10(6)/1. Three patients had cutaneous varicella zoster virus (VZV) infection within the preceding 8 weeks. All had uniocular loss of visual acuity; one also had headache and another ocular pain. All had typical retinal appearances. VZV DNA was detected in cerebrospinal fluid of four patients (and in vitreous fluid of one of the four) and in vitreous fluid of one other. One patient refused therapy and rapidly became blind. Four patients received intravenous foscarnet with intravenous aciclovir for 6 weeks: three subsequently received oral famciclovir and one oral valaciclovir; two patients also had intravitreal injections of foscarnet. In none of the four did treatment bring about improvement in visual acuity, but in all four visual loss from retinitis was halted. CONCLUSIONS: NHR occurs in HIV infected patients with advanced HIV disease and is strongly associated with evidence of VZV infection. With aggressive use of antiviral drugs the outcome is not uniformly poor. Images PMID:9582461

  1. Polymer Drug Conjugates: Recent Advancements in Various Diseases.

    PubMed

    Singh, Jasbir; Desai, Sapna; Yadav, Snehlata; Narasimhan, Balasubramanian; Kaur, Harmeet

    2016-01-01

    During the past decade, the arena of polymer therapeutics has acquired considerable interest and accompanied by advanced designs and chemical properties of polymer-drug conjugates. Various polymers, such as poly (ethylene glycol) (PEG), N-(2-hydroxypropyl) methacrylamide (HPMA), poly(glycolic acid) (PGA) and poly(lactide-co-glycolide) (PLGA) have been used successfully for clinical utilization from decades. These polymers are used in combination of drugs in such a manner that they target the specific tissues and thus the toxicity of drugs to other tissues is reduced. Presently, numerous polymer drug conjugates are under clinical trial for treatment of various diseases including cancer, diabetes, AIDS, rheumatoid arthritis etc. Many protein-polymer conjugates have been approved by FDA for clinical use but till date, no polymer-synthetic drug conjugate is approved by FDA, although many of them are undergoing final phase of clinical trials. This review highlights the recent advancements in the polymer-drug conjugates for treatment of various diseases and their preclinical and clinical status. PMID:26898741

  2. Sheep-associated malignant catarrhal fever-like skin disease in a free-ranging bighorn sheep (Ovis canadensis), Alberta, Canada

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Malignant catarrhal fever (MCF)-like clinical disease was diagnosed in a free-ranging bighorn sheep (Ovis canadensis) in Alberta, Canada. Ante-mortem observations and gross pathology included muscle atrophy, marked weight loss and focally extensive alopecia with chronic crusting hyperkeratotosis and...

  3. Declining Use of Radiotherapy in Stage I and II Hodgkin's Disease and Its Effect on Survival and Secondary Malignancies

    SciTech Connect

    Koshy, Matthew; Rich, Shayna E.; Mahmood, Usama; Kwok, Young

    2012-02-01

    Purpose: Concerns regarding long-term toxicities have led some to withhold radiotherapy (RT) for the treatment of Stage I and II Hodgkin's disease (HD). The present study was undertaken to assess the use of RT for HD and its effect on overall survival and the development of secondary malignancies. Methods and Materials: The present study included data from the Surveillance, Epidemiology, and End Results database from patients aged {>=}20 years who had been diagnosed with Stage I or II HD between 1988 and 2006. Overall survival was estimated using the Kaplan-Meier method, and the Cox multivariate regression model was used to analyze trends. Results: A total of 12,247 patients were selected, and 51.5% had received RT. The median follow-up for the present cohort was 4.9 years, with 21% of the cohort having >10 years of follow-up. Between 1988 and 1991, 62.9% had undergone RT, but between 2004 and 2006, only 43.7% had undergone RT (p < .001). The 5-year overall survival rate was 76% for patients who had not received RT and 87% for those who had (p < .001). The hazard ratio adjusted for other variables in the regression model showed that patients who had not undergone RT (hazard ratio, 1.72; 95% confidence interval, 1.72-2.02) was associated with significantly worse survival compared with patients who had received RT. The actuarial rate of developing a second malignancy was 14.6% vs. 15.0% at 15 years for those who had and had not undergone RT, respectively (p = .089). Conclusions: The present study is one of the largest studies to examine the role of RT for Stage I and II HD. Our results revealed a survival benefit with the addition of RT with no increase in the development of secondary malignancies compared with patients who had not received RT. Furthermore, the present nationwide study revealed a >20% absolute decrease in the use of RT from 1988 to 2006.

  4. [Prognostication of malignization and acute complications of gastric ulcer disease, using multiparametric neuronet clasterization].

    PubMed

    Dzyubanovskiy, I Ya; Selskiy, P R; Viytovych, L E

    2015-03-01

    Results of examination of 20 gastric ulcer disease patients were analyzed for delineation of a high risk group for an acute complications occurrence, and in whom the conduction of organ preserving preventive operative interventions is expedient. For prognostication such following indices were applied: quantity of cells-producents of various immunoglobulins, mitotic and apoptotic indices, relative volume of damaged epitheliocytes, the patients' age.

  5. Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases.

    PubMed Central

    Le Beau, M M; Espinosa, R; Neuman, W L; Stock, W; Roulston, D; Larson, R A; Keinanen, M; Westbrook, C A

    1993-01-01

    Loss of a whole chromosome 5 or a deletion of its long arm (5q) is a recurring abnormality in malignant myeloid neoplasms. To determine the location of genes on 5q that may be involved in leukemogenesis, we examined the deleted chromosome 5 homologs in a series of 135 patients with malignant myeloid diseases. By comparing the breakpoints, we identified a small segment of 5q, consisting of band 5q31, that was deleted in each patient. This segment has been termed the critical region. Distal 5q contains a number of genes encoding growth factors, hormone receptors, and proteins involved in signal transduction or transcriptional regulation. These include several genes that are good candidates for a tumor-suppressor gene, as well as the genes encoding five hematopoietic growth factors (CSF2, IL3, IL4, IL5, and IL9). By using fluorescence in situ hybridization, we have refined the localization of these genes to 5q31.1 and have determined the order of these genes and of other markers within 5q31. By hybridizing probes to metaphase cells with overlapping deletions involving 5q31, we have narrowed the critical region to a small segment of 5q31 containing the EGR1 gene. The five hematopoietic growth factor genes and seven other genes are excluded from this region. The EGR1 gene was not deleted in nine other patients with acute myeloid leukemia who did not have abnormalities of chromosome 5. By physical mapping, the minimum size of the critical region was estimated to be 2.8 megabases. This cytogenetic map of 5q31, together with the molecular characterization of the critical region, will facilitate the identification of a putative tumor-suppressor gene in this band. PMID:8516290

  6. Relationship between breast cancer and thyroid disease: relevance of autoimmune thyroid disorders in breast malignancy.

    PubMed

    Giani, C; Fierabracci, P; Bonacci, R; Gigliotti, A; Campani, D; De Negri, F; Cecchetti, D; Martino, E; Pinchera, A

    1996-03-01

    The relationship between thyroid dysfunction and breast cancer (BC) is debated. To clarify this controversial issue, a prospective study on thyroid function in BC was performed. The prevalence of thyroid disease was examined in 102 consecutive BC patients with ductal infiltrating carcinoma after surgery and before starting any chemohormonal or x-ray therapy and in 100 age-matched control healthy women living in the same borderline iodine-sufficient geographic area. All subjects were submitted to clinical ultrasound thyroid evaluation and serum free T4, free T3, TSH, thyroperoxidase antibody, and thyroglobulin antibody determination. Fine needle aspiration was performed in all thyroid nodules. Estrogen and progesterone receptors (ER and PR, respectively) were assayed in 92 and 55 BC specimens, respectively. The overall prevalence of thyroid disease was 47 in 102 (46%) in BC patients and 14 in 100 (14%) in controls (P < 0.0001). The prevalence of nontoxic goiter was 27.4% in BC patients and 11% in controls (P = 0.003). Hashimoto's thyroiditis was found in 13.7% of BC patients and in only 2% of the controls (P < 0.005). Other thyroid disorders found in the BC group included 2 cases of Graves' disease, 2 of thyroid carcinoma, and 1 of subacute thyroiditis, whereas in the control group only 1 case of Graves' disease and none of the other disorders were found. Mean free T3, free T4, and TSH concentrations showed no difference between BC patients and controls. The prevalence of thyroperoxidase antibody was higher in BC patients than in controls (23.5% vs. 8%; P < 0.005), whereas the prevalence of thyroglobulin antibody was not different. In BC patients the presence of thyroid antibodies was more frequently associated with clinically detectable autoimmune thyroiditis (14 of 26, 51.8%; P = 0.03) and was more common in the younger group. The positivity of ER was found in 51 of 92 (55.43%) and that of PR was found in 26 of 55 (47.27%) BC specimens. No relationship was found

  7. Angiolymphoid hyperplasia with eosinophilia: a disease that may be confused with malignancy.

    PubMed

    Barnes, L; Koss, W; Nieland, M L

    1980-01-01

    Twelve new cases of an unusual, benign vasoproliferative and inflammatory disorder of unknown etiology, angiolymphoid hyperplasia with eosinophilia (ALHE), are described and contrasted clinically and pathologically with those appearing in the literature. Only recently recognized in the United States, the disease is of singular importance because the vascular component may be confused histologically with angiosarcoma, thereby resulting in unwarranted aggressive therapeutic measures. ALHE characteristically affects adults and presents in the head and neck region as either solitary or multiple cutaneous tumors. The lesions are pruritic, frequently bleed after minor trauma, and may be associated with peripheral eosinophilia and regional lymphadenopathy. On rare occasions, the disease may masquerade as a salivary-gland tumor, cause stenosis of the external auditory canal, or present as an osseous lesion of the skull. Extrafacial tumors are uncommon. Excision is the most frequent form of therapy; however, local irradiation, corticosteroids, electrodessication with curettage, and chemotherapy have also had varying degrees of success.

  8. Anaesthetic management of coronary artery bypass grafting in a patient with central core disease and susceptibility to malignant hyperthermia on statin therapy.

    PubMed

    Johi, R R; Mills, R; Halsall, P J; Hopkins, P M

    2003-11-01

    Central core disease and malignant hyperthermia (MH) are both associated with mutations in the RYR1 gene. We report the anaesthetic management of one such patient presenting for coronary artery bypass grafting. Her medication included aspirin 75 mg, atorvastatin 20 mg, isosorbide mononitrate 60 mg, atenolol 25 mg and glyceryl trinitrite sublingual spray as required. The use of aprotinin, statins and moderate hypothermia in patients with central core disease and known susceptibility to MH has not been documented.

  9. Human BK Polyomavirus—The Potential for Head and Neck Malignancy and Disease

    PubMed Central

    Burger-Calderon, Raquel; Webster-Cyriaque, Jennifer

    2015-01-01

    Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV) has conclusively been linked to human cancer, all members of the polyomavirus (PyV) family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV) in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD). HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future. PMID:26184314

  10. Human BK Polyomavirus-The Potential for Head and Neck Malignancy and Disease.

    PubMed

    Burger-Calderon, Raquel; Webster-Cyriaque, Jennifer

    2015-07-08

    Members of the human Polyomaviridae family are ubiquitous and pathogenic among immune-compromised individuals. While only Merkel cell polyomavirus (MCPyV) has conclusively been linked to human cancer, all members of the polyomavirus (PyV) family encode the oncoprotein T antigen and may be potentially carcinogenic. Studies focusing on PyV pathogenesis in humans have become more abundant as the number of PyV family members and the list of associated diseases has expanded. BK polyomavirus (BKPyV) in particular has emerged as a new opportunistic pathogen among HIV positive individuals, carrying harmful implications. Increasing evidence links BKPyV to HIV-associated salivary gland disease (HIVSGD). HIVSGD is associated with elevated risk of lymphoma formation and its prevalence has increased among HIV/AIDS patients. Determining the relationship between BKPyV, disease and tumorigenesis among immunosuppressed individuals is necessary and will allow for expanding effective anti-viral treatment and prevention options in the future.

  11. Advances in stem cell therapy for cardiovascular disease (Review).

    PubMed

    Sun, Rongrong; Li, Xianchi; Liu, Min; Zeng, Yi; Chen, Shuang; Zhang, Peying

    2016-07-01

    Cardiovascular disease constitutes the primary cause of mortality and morbidity worldwide, and represents a group of disorders associated with the loss of cardiac function. Despite considerable advances in the understanding of the pathologic mechanisms of the disease, the majority of the currently available therapies remain at best palliative, since the problem of cardiac tissue loss has not yet been addressed. Indeed, few therapeutic approaches offer direct tissue repair and regeneration, whereas the majority of treatment options aim to limit scar formation and adverse remodeling, while improving myocardial function. Of all the existing therapeutic approaches, the problem of cardiac tissue loss is addressed uniquely by heart transplantation. Nevertheless, alternative options, particularly stem cell therapy, has emerged as a novel and promising approach. This approach involves the transplantation of healthy and functional cells to promote the renewal of damaged cells and repair injured tissue. Bone marrow precursor cells were the first cell type used in clinical studies, and subsequently, preclinical and clinical investigations have been extended to the use of various populations of stem cells. This review addresses the present state of research as regards stem cell therapy for cardiovascular disease.

  12. Synchronous bilateral primary breast malignant phyllodes tumor and carcinoma of the breast with Paget’s disease: a case report and review of the literature

    PubMed Central

    Zhao, Hongyuan; Cheng, Xiaoming; Sun, Suhong; Yang, Weiming; Kong, Fanli; Zeng, Feng

    2015-01-01

    Synchronous bilateral primary breast malignant phyllodes tumor or/and carcinoma of the breast with Paget’s disease is rare. In the article, we present a case of bilateral carcinoma of the breast with Paget’s disease of the right breast and malignant phyllodes tumor of the left breast. A 44-years-old Chinese woman presented with a 1 month history of the right breast nipple with eczema and fester and growing and palpable mass of left breast. Molybdenum target X-ray revealed microcalcification in the right breast, which was highly suspected of malignant tumor, and round-like mass with smooth surface and homogeneous density in the left breast. Color ultrasound showed a lobulated lump which circumferential blood flows around in the left breast, and which did not show any mass in the right breast. The patient was undertaken the bilateral modified radical mastectomy. The histological diagnosis was Paget’s disease associated with infiltrating ductal carcinoma in the right breast and malignant phyllodes tumor the left breast. The patient also received 6 cycles of the postoperative adjuvant chemotherapy by using T.T. regimen comprised docetaxel (100 mg) and pirarubicin (60 mg). PMID:26770378

  13. Timing of the loss of Pten protein determines disease severity in a mouse model of myeloid malignancy

    PubMed Central

    Yan, Yan; Webster, Cody; Shao, Lijian; Lensing, Shelly Y.; Ni, Hongyu; Feng, Wei; Colorado, Natalia; Pathak, Rupak; Xiang, Zhifu; Hauer-Jensen, Martin; Li, Shaoguang; Zhou, Daohong; Emanuel, Peter D.

    2016-01-01

    Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric mixed myelodysplastic/myeloproliferative neoplasm (MDS/MPN). JMML leukemogenesis is linked to a hyperactivated RAS pathway, with driver mutations in the KRAS, NRAS, NF1, PTPN11, or CBL genes. Previous murine models demonstrated how those genes contributed to the selective hypersensitivity of JMML cells to granulocyte macrophage–colony-stimulating factor (GM-CSF), a unifying characteristic in the disease. However, it is unclear what causes the early death in children with JMML, because transformation to acute leukemia is rare. Here, we demonstrate that loss of Pten (phosphatase and tensin homolog) protein at postnatal day 8 in mice harboring Nf1 haploinsufficiency results in an aggressive MPN with death at a murine prepubertal age of 20 to 35 days (equivalent to an early juvenile age in JMML patients). The death in the mice was due to organ infiltration with monocytes/macrophages. There were elevated activities of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) in cells at physiological concentrations of GM-CSF. These were more pronounced in mice with Nf1 haploinsufficiency than in littermates with wild-type Nf1, but this model is insufficient to cause cells to be GM-CSF hypersensitive. This new model represents a murine MPN model with features of a pediatric unclassifiable mixed MDS/MPN and mimics many clinical manifestations of JMML in terms of age of onset, aggressiveness, and organ infiltration with monocytes/macrophages. Our data suggest that the timing of the loss of PTEN protein plays a critical role in determining the disease severity in myeloid malignancies. This model may be useful for studying the pathogenesis of pediatric diseases with alterations in the Ras pathway. PMID:26764354

  14. Clostridium difficile infection in patients with haematological malignant disease. Risk factors, faecal toxins and pathogenic strains.

    PubMed Central

    Heard, S. R.; Wren, B.; Barnett, M. J.; Thomas, J. M.; Tabaqchali, S.

    1988-01-01

    Two hundred and forty-eight patients from shared oncology and general medical wards were prospectively studied over a 6-month period for carriage of Clostridium difficile during an outbreak of clinical disease with an epidemic strain of the organism. Risk factors for infection were assessed. Acute leukaemia and/or its treatment were identified as significantly increasing the risk of infection. The relationship between the type of C. difficile isolated (as defined by a typing system based on the incorporation of [35S]methionine into bacterial proteins followed by gel electrophoresis), the presence of faecal toxins A and B and clinical symptoms were analysed. Carriage of the epidemic strain, type X, had a significant association with symptoms amongst oncology patients, with two thirds of these patients having detectable faecal toxin A and one third detectable faecal toxin B. During an outbreak of C. difficile-associated disease, typing the organism and assaying for both faecal toxins in symptomatic patients may be of benefit in determining which patients require specific, urgent treatment. PMID:3123260

  15. [Intracytoplasmic lumina of benign and malignant breast diseases--a light and electron microscopic study].

    PubMed

    Gu, C M

    1990-07-01

    Intracytoplasmic lumina (ICLs) of 70 cases with breast carcinoma and 29 cases with benign breast diseases were observed by light and electron microscopy. ICLs were morphologically divided into two types. Type A was characterized by the presence of secretory materials stained with eosin in the lumen and Type B by the cytoplasmic vacuoles under light microscope. Electron microscopic observation on Type A ICLs showed numerous filiform microvilli projecting towards the lumen and various amounts of secretory materials in the lumen. Type B of ICLs only had scanty and short microvilli and rarely secretory materials in the lumen. The results indicated that: 1. The frequency of ICLs in breast cancer was significantly higher than that in benign breast disease (P less than 0.01). 2. The frequency of ICLs in breast cancer showed strong negative correlation with its histological grades but not with its histological types. 3. ICLs had similar frequency under both light and electron microscopes. As a relatively specific structure in breast carcinoma cells, ICLs may be helpful in the diagnosis of breast carcinoma and establishment of the breast origin for metastatic carcinoma. PMID:2176965

  16. Malignant Pleural Effusion: Medical Approaches for Diagnosis and Management

    PubMed Central

    2014-01-01

    Malignant pleural effusions (MPEs) are the second leading cause of exudative pleural effusions after parapneumonic effusions. In the vast majority of cases, a MPE signifies incurable disease associated with high morbidity and mortality. Considerable advances have been made for the diagnosis of MPEs, through the development of improved methods in the specialized cytological and imaging studies. The cytological or histological confirmation of malignant cells is currently important in establishing a diagnosis. Furthermore, despite major advancements in cancer treatment for the past two decades, management of MPE remains palliative. This article presents a comprehensive review of the medical approaches for diagnosis and management of MPE. PMID:24920947

  17. Advanced gastrointestinal endoscopic imaging for inflammatory bowel diseases

    PubMed Central

    Tontini, Gian Eugenio; Rath, Timo; Neumann, Helmut

    2016-01-01

    Gastrointestinal luminal endoscopy is of paramount importance for diagnosis, monitoring and dysplasia surveillance in patients with both, Crohn’s disease and ulcerative colitis. Moreover, with the recent recognition that mucosal healing is directly linked to the clinical outcome of patients with inflammatory bowel disorders, a growing demand exists for the precise, timely and detailed endoscopic assessment of superficial mucosal layer. Further, the novel field of molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy, now encompassing not only diagnosis, surveillance, and treatment but also the prediction of individual therapeutic responses. Within this review, we describe how novel endoscopic approaches and advanced endoscopic imaging methods such as high definition and high magnification endoscopy, dye-based and dye-less chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and molecular imaging now allow for the precise and ultrastructural assessment of mucosal inflammation and describe the potential of these techniques for dysplasia detection. PMID:26811662

  18. CAP--advancing the evaluation of preclinical Alzheimer disease treatments.

    PubMed

    Reiman, Eric M; Langbaum, Jessica B; Tariot, Pierre N; Lopera, Francisco; Bateman, Randall J; Morris, John C; Sperling, Reisa A; Aisen, Paul S; Roses, Allen D; Welsh-Bohmer, Kathleen A; Carrillo, Maria C; Weninger, Stacie

    2016-01-01

    If we are to find treatments to postpone, reduce the risk of, or completely prevent the clinical onset of Alzheimer disease (AD), we need faster methods to evaluate promising preclinical AD treatments, new ways to work together in support of common goals, and a determination to expedite the initiation and performance of preclinical AD trials. In this article, we note some of the current challenges, opportunities and emerging strategies in preclinical AD treatment. We describe the Collaboration for Alzheimer's Prevention (CAP)-a convening, harmonizing and consensus-building initiative to help stakeholders advance AD prevention research with rigour, care and maximal impact-and we demonstrate the impact of CAP on the goals and design of new preclinical AD trials.

  19. Recent advancement of therapeutic endoscopy in the esophageal benign diseases.

    PubMed

    Bechara, Robert; Inoue, Haruhiro

    2015-05-16

    Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy (POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus. PMID:25992187

  20. Recent advancement of therapeutic endoscopy in the esophageal benign diseases

    PubMed Central

    Bechara, Robert; Inoue, Haruhiro

    2015-01-01

    Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy (POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus. PMID:25992187

  1. Effect of disease burden on health-related quality of life in patients with malignant gliomas.

    PubMed Central

    Osoba, D.; Brada, M.; Prados, M. D.; Yung, W. K.

    2000-01-01

    The burden imposed by disease recurrence in patients with high-grade gliomas is not well documented. We studied the frequency of self-report symptoms and the effects on health-related quality of life in patients who had recurrent glioblastoma multiforme or anaplastic astrocytoma and who had a Karnofsky performance score > or = 70. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items (QLQ-C30) and the Brain Cancer Module (BCM20) before initiation of treatment for first recurrence of disease. Six symptoms (fatigue, uncertainty about the future, motor difficulties, drowsiness, communication difficulties, and headache) were reported with a frequency > 50% by both groups of patients. An additional two symptoms (visual problems and pain) were also reported with frequencies of > 50% by patients with recurrent glioblastoma multiforme. Most of the symptoms were likely due to recurrence, but previous radiation therapy and on-going corticosteroid treatment may have also been casual factors for fatigue, whereas uncertainty about the future and pain were probably nonspecific for brain cancer. Problems with motor functioning, vision, leg strength, and pain were reported more frequently by patients with recurrent glioblastoma multiforme than by those with recurrent anaplastic astrocytoma. Scores on health-related quality-of-life functioning scales were similar in the two groups. Finally, the scores for patients who had recurrent high-grade gliomas and a Karnofsky performance score > or = 70 were compared with the reported health-related quality of life scores of patients with other cancers. Their scores were similar to those of patients with metastatic cancers and worse than those of patients with localized cancers. PMID:11265231

  2. Central Nervous System Disease in Hematological Malignancies: Historical Perspective and Practical Applications

    PubMed Central

    Pui, Ching-Hon; Thiel, Eckhard

    2009-01-01

    Acute lymphoblastic leukemia (ALL) 5-year survival rates are approaching 90% in children and 50% in adults who are receiving contemporary risk-directed treatment protocols. Current efforts focus not only on further improving cure rate but also on patient quality of life. Hence, all protocols decrease or limit the use of cranial irradiation as central nervous system (CNS)-directed therapy, even in patients with high-risk presenting features, such as the presence of leukemia cells in the cerebrospinal fluid (even resulting from traumatic lumbar puncture), adverse genetic features, T-cell immunophenotype, and a large leukemia-cell burden. Current strategies for CNS-directed therapy involve effective systemic chemotherapy (eg, dexamethasone, high-dose methotrexate, intensive asparaginase, ifosfamide) and early intensification and optimization of intrathecal therapy. Options under investigation for the treatment of relapsed or refractory CNS leukemia in ALL patients include thiotepa and intrathecal liposomal cytarabine. CNS involvement in non-Hodgkin’s lymphoma (NHL) is associated with young age, advanced stage, number of extranodal sites, elevated lactate dehydrogenase, and International Prognostic Index score. Refractory CNS lymphoma in patients with NHL carries a poor prognosis, with a median survival of 2 to 6 months; the most promising treatment, autologous stem cell transplant, can extend median survival from 10 to 26 months. CNS prophylaxis is required during the initial treatment of NHL subtypes that carry a high risk of CNS relapse, such as B-cell ALL, Burkitt’s lymphoma, and lymphoblastic lymphoma. The use of CNS prophylaxis in the treatment of diffuse large B-cell lymphoma is controversial because of the low risk of CNS relapse (~5%) in this population. In this article, we review current and past practice of intrathecal therapy in ALL and NHL and the risk-models that aim to identify predictors of CNS relapse in NHL. PMID:19660680

  3. Chromosome aberrations in lymphocytes from women irradiated for benign and malignant gynecological disease

    SciTech Connect

    Kleinerman, R.A.; Boice, J.D. Jr.; Inskip, P.D.; Tarone, R.E.; Littlefield, L.G.; Sayer, A.M.; Cookfair, D.L.; Wactawski-Wende, J.

    1994-07-01

    Excess leukemias have occurred after partial-body radiotherapy for cervical cancer and benign gynecological disease (BGD). However, the level of risk is nearly the same in both groups, about twofold, despite a tenfold difference in average dose to active bone marrow. High-dose cell killing has been postulated as one explanation for this apparent inconsistency. To examine whether chromosome aberration rates observed in lymphocytes many years after exposure might serve as population markers of cancer risk, blood samples were taken from 60 women treated for BGD (34 with radiation) and cytogenetic data compared with previous results from 96 women irradiated for cervical cancer. Remarkably, the rate of stable aberrations, which reflects nonlethal damage in surviving stem cells, was only slightly higher among the cancer patients. Thus the lower-dose regimens to treat benign disorders resulted in much higher aberration yields per unit dose than those for cervical cancer. Assuming that the fraction of cytogenetically aberrant stem cells that survive radiotherapy contributes to the leukemogenic process, these data are then consistent with the epidemiological observations of comparable overall leukemia risks seen in these two irradiated populations. Accordingly, for patient populations given partial-body radiotherapy, stable aberrations at a long time after exposure appear to serve as biomarkers of effective risk rather than as biomarkers of radiation dose received. 30 refs., 4 tabs.

  4. Oral ciclopirox olamine displays biological activity in a phase I study in patients with advanced hematologic malignancies.

    PubMed

    Minden, Mark D; Hogge, Donna E; Weir, Scott J; Kasper, Jim; Webster, Debra A; Patton, Lavonne; Jitkova, Yulia; Hurren, Rose; Gronda, Marcela; Goard, Carolyn A; Rajewski, Lian G; Haslam, John L; Heppert, Kathleen E; Schorno, Kevin; Chang, Hong; Brandwein, Joseph M; Gupta, Vikas; Schuh, Andre C; Trudel, Suzanne; Yee, Karen W L; Reed, Gregory A; Schimmer, Aaron D

    2014-04-01

    The antimycotic ciclopirox olamine is an intracellular iron chelator that has anticancer activity in vitro and in vivo. We developed an oral formulation of ciclopirox olamine and conducted the first-in-human phase I study of this drug in patients with relapsed or refractory hematologic malignancies (Trial registration ID: NCT00990587). Patients were treated with 5-80 mg/m² oral ciclopirox olamine once daily for five days in 21-day treatment cycles. Pharmacokinetic and pharmacodynamic companion studies were performed in a subset of patients. Following definition of the half-life of ciclopirox olamine, an additional cohort was enrolled and treated with 80 mg/m² ciclopirox olamine four times daily. Adverse events and clinical response were monitored throughout the trial. Twenty-three patients received study treatment. Ciclopirox was rapidly absorbed and cleared with a short half-life. Plasma concentrations of an inactive ciclopirox glucuronide metabolite were greater than those of ciclopirox. Repression of survivin expression was observed in peripheral blood cells isolated from patients treated once daily with ciclopirox olamine at doses greater than 10 mg/m², demonstrating biological activity of the drug. Dose-limiting gastrointestinal toxicities were observed in patients receiving 80 mg/m² four times daily, and no dose limiting toxicity was observed at 40 mg/m² once daily. Hematologic improvement was observed in two patients. Once-daily dosing of oral ciclopirox olamine was well tolerated in patients with relapsed or refractory hematologic malignancies, and further optimization of dosing regimens is warranted in this patient population. PMID:24273151

  5. Malignant mesothelioma in 2004: How advanced technology and new drugs are changing the perspectives of mesothelioma patients. Highlights from the VIIth Meeting of the International Mesothelioma Interest Group.

    PubMed

    Porta, C; Ardizzoni, A; Gaudino, G; Maio, M; Mutti, L; Pinto, C; Porru, S; Puntoni, R; Tassi, G; Tognon, M

    2005-01-01

    Malignant mesothelioma (MMe) is a seemingly uncommon tumour whose incidence has in fact increased steadily and progressively over the last 30 years. Indeed, an actual "epidemic" is expected in the next 20 years, with over 1300 new cases a year till 2020 at least. Despite unquestionable improvement in the diagnostic methods at our disposal and the availability of new treatment strategies, the prognosis of MMe patients remains dramatically poor. For all the above reasons, translational research is the key to success; indeed, ever increasing knowledge of the molecular mechanisms underlying MMe pathogenesis could lead (and is actually leading) to new, hopefully more active, treatment options. To foster discussion among investigators working in this field, and to exchange different viewpoints concerning the newest advances in MMe pathogenesis and treatment, the VII International Mesothelioma Interest Group (IMIG) meeting was held in Brescia (Italy) between 24 and 26 June 2004 in cooperation with the Italian Group for the Study and Therapy of MMe (GIMe). The aim of this report is to summarize the most significant advances in the different disciplines applied to MMe presented and discussed during the IMIG meeting and how these advances will be changing the perspective of patients with MMe.

  6. Advances in the treatment of cognitive impairment in Parkinson's disease.

    PubMed

    Goldman, Jennifer G; Weintraub, Daniel

    2015-09-15

    Cognitive impairment in Parkinson's disease (PD) is a frequent complication, with significant interindividual variability in clinical symptoms, severity, timing, and neural substrates. Recent studies have focused not only on understanding PD dementia, but also mild cognitive impairment in PD, which may represent a prodromal stage for dementia. In recent years, there have been important advances regarding clinical characterizations, definitions, associated biomarkers, and risk factors for both mild cognitive impairment in PD and PD dementia. However, there is a paucity of effective therapies for cognitive impairment in PD, whether for mild symptoms or for moderate to severe dementia. At present, only rivastigmine is U.S. Food and Drug Administration approved for PD dementia, an indication received nearly a decade ago. Given the frequency of PD cognitive impairment and its substantial impact on both patients and families, the lack of available and effective treatments represents a striking gap in the field, especially when compared to the large number of available therapies for PD motor symptoms and complications. Improved symptomatic therapies, as well as potential disease-modifying agents, for PD cognitive impairment are needed. Most therapeutic trials for PD dementia and mild cognitive impairment in PD have focused on drugs developed for and tested in Alzheimer's disease, such as cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist, memantine, though recent and ongoing trials examine the effects of pharmacological agents affecting other neurotransmitters, as well as nonpharmacological therapies, including mental and physical exercise and neurostimulation. This review summarizes the design and outcomes of trials for PD cognitive impairment published since 2013 and highlights future therapeutic research opportunities and challenges.

  7. The Malignant Protein Puzzle.

    PubMed

    Walker, Lary C; Jucker, Mathias

    2016-01-01

    When most people hear the words malignant and brain, cancer immediately comes to mind. But our authors argue that proteins can be malignant too, and can spread harmfully through the brain in neurodegenerative diseases that include Alzheimer's, Parkinson's, CTE, and ALS. Studying how proteins such as PrP, amyloid beta, tau, and others aggregate and spread, and kill brain cells, represents a crucial new frontier in neuroscience. PMID:27408676

  8. Chronic advanced liver disease and impotence: cause and effect?

    PubMed

    Cornely, C M; Schade, R R; Van Thiel, D H; Gavaler, J S

    1984-01-01

    The prevalence of impotence is increased in males who chronically abuse alcohol. Further, impotence may occur in the absence of liver disease in such men. In contrast, no data is available concerning the prevalence of impotence in nonalcoholic men with advanced liver disease. To investigate the relationship between alcohol and impotence in cirrhotic men, a self-administered questionnaire was completed by male alcoholic cirrhotics admitted to the medical service as well as by nonalcoholic cirrhotic liver transplant candidates admitted to the medical and surgical services of Presbyterian-University Hospital. Each participant was asked whether or not he had experienced impotence and if so, to report the frequency and duration of his impotence. The frequency of impotence was recorded on a weighted scale with four gradations: 4 = always; 3 = usually; 2 = sometimes; 1 = seldom. In addition, measures of hepatic injury and function as well as measures of the functional integrity of the hypothalamic-pituitary-gonadal axis for each subject evaluated were obtained. Fourteen of the 20 alcoholics with cirrhosis and 10 of the 40 nonalcoholic liver transplant candidates with cirrhosis reported a history of impotence. The association between impotence and alcohol abuse was significant. The impotence index developed by multiplying the frequency by the duration of impotency for each individual demonstrated a more severe degree of impotence in the alcoholics as compared to the nonalcoholics (p less than 0.01). The alcoholics also had lower plasma levels of testosterone and greater plasma levels of gonadotropins as compared to the nonalcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Recent Advances in Traditional Chinese Medicine for Kidney Disease.

    PubMed

    Zhong, Yifei; Menon, Madhav C; Deng, Yueyi; Chen, Yiping; He, John Cijiang

    2015-09-01

    Because current treatment options for chronic kidney disease (CKD) are limited, many patients seek out alternative therapies such as traditional Chinese medicine. However, there is a lack of evidence from large clinical trials to support the use of traditional medicines in patients with CKD. Many active components of traditional medicine formulas are undetermined and their toxicities are unknown. Therefore, there is a need for research to identify active compounds from traditional medicines and understand the mechanisms of action of these compounds, as well as their potential toxicity, and subsequently perform well-designed, randomized, controlled, clinical trials to study the efficacy and safety of their use in patients with CKD. Significant progress has been made in this field within the last several years. Many active compounds have been identified by applying sophisticated techniques such as mass spectrometry, and more mechanistic studies of these compounds have been performed using both in vitro and in vivo models. In addition, several well-designed, large, randomized, clinical trials have recently been published. We summarize these recent advances in the field of traditional medicines as they apply to CKD. In addition, current barriers for further research are also discussed. Due to the ongoing research in this field, we believe that stronger evidence to support the use of traditional medicines for CKD will emerge in the near future.

  10. Immunology of malignant diseases

    SciTech Connect

    Byers, V.S.; Baldwin, R.W.

    1987-01-01

    This book contains 11 chapters. Some of the chapter titles are: Immunoscintigraphy: tumor detection with radiolabelled antitumor monoclonal antibodies; Bone marrow transplantation; Immunomodulating agents; Immunology in bowel cancer; Melanoma; and Immunological features of human bladder cancer.

  11. [Immunotherapy of malignant diseases].

    PubMed

    Dorval, T; Michon, J; Tartour, E; Fridman, W H

    1995-01-01

    Cancer immunotherapy has been carried out since the early fifties and first involved nonspecific system (BCG, Corynebacterium parvum, levamisole...). More recently, the production of cytokines as interferons or interleukin 2, the introduction of monoclonal antibodies have allowed a new development to cancer immunotherapy. Nevertheless, these new approaches have to be considered as a step in the biological therapy of cancer.

  12. [Immunotherapy of malignant diseases].

    PubMed

    Dorval, T; Michon, J; Tartour, E; Fridman, W H

    1995-01-01

    Cancer immunotherapy has been carried out since the early fifties and first involved nonspecific system (BCG, Corynebacterium parvum, levamisole...). More recently, the production of cytokines as interferons or interleukin 2, the introduction of monoclonal antibodies have allowed a new development to cancer immunotherapy. Nevertheless, these new approaches have to be considered as a step in the biological therapy of cancer. PMID:7542946

  13. Common electrolyte imbalances associated with malignancy.

    PubMed

    Hawthorne, J L; Schneider, S M; Workman, M L

    1992-08-01

    More than one million Americans will be diagnosed with cancer during 1992, and 50% will be cured of their disease. Of those individuals not cured of the malignancy, survival time after diagnosis has increased tremendously compared to 1980. Because of advances in therapy and the increase in long-term survival, the presence of cancer patients in critical care units should no longer represent either a medical contradiction or an ethical dilemma when the condition requiring critical care is potentially reversible. Many of these individuals may become patients in critical care settings as a result of specific electrolyte imbalances caused by the malignant disease or treatment of malignancy. Although the imbalances often are temporary, they can be life-threatening without intervention. The most common temporary electrolyte imbalances associated with malignant conditions are hypercalcemia, hyperkalemia, and tumor lysis syndrome. Critical care nurses can contribute skill and knowledge in ameliorating these conditions so that the person with cancer can have better quality and longer survival time.

  14. Malignant biliary obstruction: From palliation to treatment.

    PubMed

    Boulay, Brian R; Birg, Aleksandr

    2016-06-15

    Malignant obstruction of the bile duct from cholangiocarcinoma, pancreatic adenocarcinoma, or other tumors is a common problem which may cause debilitating symptoms and increase the risk of subsequent surgery. The optimal treatment - including the decision whether to treat prior to resection - depends on the type of malignancy, as well as the stage of disease. Preoperative biliary drainage is generally discouraged due to the risk of infectious complications, though some situations may benefit. Patients who require neoadjuvant therapy will require decompression for the prolonged period until attempted surgical cure. For pancreatic cancer patients, self-expanding metallic stents are superior to plastic stents for achieving lasting decompression without stent occlusion. For cholangiocarcinoma patients, treatment with percutaneous methods or nasobiliary drainage may be superior to endoscopic stent placement, with less risk of infectious complications or failure. For patients of either malignancy who have advanced disease with palliative goals only, the choice of stent for endoscopic decompression depends on estimated survival, with plastic stents favored for survival of < 4 mo. New endoscopic techniques may actually extend stent patency and patient survival for these patients by achieving local control of the obstructing tumor. Both photodynamic therapy and radiofrequency ablation may play a role in extending survival of patients with malignant biliary obstruction.

  15. Sequential Stenting for Extensive Malignant Airway Stenosis

    PubMed Central

    Takahama, Makoto; Nakajima, Ryu; Kimura, Michitaka; Tei, Keiko; Yamamoto, Ryoji

    2014-01-01

    Purpose: Malignant airway stenosis extending from the bronchial bifurcation to the lower lobar orifice was treated with airway stenting. We herein examine the effectiveness of airway stenting for extensive malignant airway stenosis. Methods: Twelve patients with extensive malignant airway stenosis underwent placement of a silicone Dumon Y stent (Novatech, La Ciotat, France) at the tracheal bifurcation and a metallic Spiral Z-stent (Medico’s Hirata, Osaka, Japan) at either distal side of the Y stent. We retrospectively analyzed the therapeutic efficacy of the sequential placement of these silicone and metallic stents in these 12 patients. Results: The primary disease was lung cancer in eight patients, breast cancer in two patients, tracheal cancer in one patient, and thyroid cancer in one patient. The median survival period after airway stent placement was 46 days. The Hugh–Jones classification and performance status improved in nine patients after airway stenting. One patient had prolonged hemoptysis and died of respiratory tract hemorrhage 15 days after the treatment. Conclusion: Because the initial disease was advanced and aggressive, the prognosis after sequential airway stent placement was significantly poor. However, because respiratory distress decreased after the treatment in most patients, this treatment may be acceptable for selected patients with extensive malignant airway stenosis. PMID:25273272

  16. Malignant biliary obstruction: From palliation to treatment.

    PubMed

    Boulay, Brian R; Birg, Aleksandr

    2016-06-15

    Malignant obstruction of the bile duct from cholangiocarcinoma, pancreatic adenocarcinoma, or other tumors is a common problem which may cause debilitating symptoms and increase the risk of subsequent surgery. The optimal treatment - including the decision whether to treat prior to resection - depends on the type of malignancy, as well as the stage of disease. Preoperative biliary drainage is generally discouraged due to the risk of infectious complications, though some situations may benefit. Patients who require neoadjuvant therapy will require decompression for the prolonged period until attempted surgical cure. For pancreatic cancer patients, self-expanding metallic stents are superior to plastic stents for achieving lasting decompression without stent occlusion. For cholangiocarcinoma patients, treatment with percutaneous methods or nasobiliary drainage may be superior to endoscopic stent placement, with less risk of infectious complications or failure. For patients of either malignancy who have advanced disease with palliative goals only, the choice of stent for endoscopic decompression depends on estimated survival, with plastic stents favored for survival of < 4 mo. New endoscopic techniques may actually extend stent patency and patient survival for these patients by achieving local control of the obstructing tumor. Both photodynamic therapy and radiofrequency ablation may play a role in extending survival of patients with malignant biliary obstruction. PMID:27326319

  17. Malignant adenolymphoma.

    PubMed

    Moosavi, H; Ryan, C; Schwartz, S; Donnelly, J A

    1980-01-01

    Adenolymphoma (Warthin's tumor) is a well studied benign tumor of the salivary gland. Malignant transformation of such a tumor is rare and not well documented in the literature. The light microscopic and ultrastructural features of an undifferentiated carcinoma arising in an adenolymphoma in the parotid gland of a middle aged male are described, and the relevant literature is reviewed. Similarities between the benign adenolymphoma and the undifferentiated malignant tumor, such as the presence of interstitial lymphoplasmacytic cell infiltrates, dark and light epithelial cells, similar cytoplasmic organelles, and nuclear morphology, suggest a malignant transformation of a previously existing benign adenolymphoma.

  18. Hypercalcemia of malignancy and new treatment options.

    PubMed

    Sternlicht, Hillel; Glezerman, Ilya G

    2015-01-01

    Hypercalcemia of malignancy affects up to one in five cancer patients during the course of their disease. It is associated with both liquid malignancies, commonly multiple myeloma, leukemia, and non-Hodgkins lymphoma and solid cancers, particularly breast and renal carcinomas as well as squamous cell carcinomas of any organ. The clinical manifestations of hypercalcemia are generally constitutional in nature and not specific to the inciting malignancy. Such physical manifestations can range from malaise to lethargy and confusion. Constipation and anorexia are common. Acute kidney injury is likely the most frequently encountered manifestation of end organ damage. Symptomatology is closely linked to both the absolute elevation of serum calcium levels and the rapidity of calcium rise. The majority of cases are humoral in etiology and related to parathyroid hormone-related protein (PTHrP). Approximately 20% of cases are the result of direct bone metastasis with extra-renal 1,25-dihydroxyvitamin D (calcitriol) and ectopic parathyroid hormone production likely accounting for less than 1% of cases. The diagnosis of hypercalcemia of malignancy is confirmed either by an elevated PTHrP or by an evidence of bone metastasis in the appropriate clinical setting. Treatment is predicated on the patient's symptoms and absolute serum calcium level. Interventions are aimed at lowering the serum calcium concentration by inhibiting bone resorption and increasing urinary calcium excretion, the former accomplished via bisphosphonate therapy and the latter with aggressive hydration. Novel therapies for refractory disease include denosumab, a monoclonal antibody against the receptor activator of nuclear factor κB ligand, and the calcimimetic cinacalcet. Finally, anti-PTHrP antibodies have been successfully deployed in animal models of disease. Despite the efficacy of the above therapies, hypercalcemia of malignancy portends an ominous prognosis, indicating advanced and often refractory

  19. Chest CT with iterative reconstruction algorithms for airway stent evaluation in patients with malignant obstructive tracheobronchial diseases.

    PubMed

    Li, Tingting; Zhang, Yonggao; Wang, Yadong; Gao, Jianbo; Jiang, Yan

    2016-09-01

    The aim of the study was to investigate the image quality of low-dose CT images with different reconstruction algorithms including filtered back projection (FBP), hybrid iterative reconstruction (HIR), and iterative model reconstruction (IMR) algorithms by comparison of routine dose images with FBP reconstruction, in patients with malignant obstructive tracheobronchial diseases.In total, 60 patients (59 ± 9.3 years, 37 males) with airway stent who are randomly assigned into 2 groups (routine-dose [RD] and low-dose [LD] group, 30 for each) underwent chest CT on a 256-slice CT (RD-group 120 kV, 250 mAs, LD-group 120 kV, 120 mAs). Images were reconstructed with filtered back projection (FBP) algorithm in the RD group, whereas with FBP, HIR and IMR algorithms in the LD group. Effective radiation dose of both groups was recorded. Image-quality assessment was performed by 2 radiologists according to structure demarcation near stents, artifacts, noise, and diagnostic confidence using a 5-point scale (1 [poor] to 5 [excellent]). Image noise and CNR were measured.The effective radiation dose of LD group was reduced 52.7% compared with the RD group (10.8 mSv ± 0.58 vs 5.1 mSv ± 0.26, P = 0.00). LD-IMR images enabled lowest image noise and best subjective image quality scores of all 4 indices, when compared with RD images reconstructed with FBP (RD-FBP) images (all P < 0.05). LD images reconstructed with and with HIR (LD-HIR) images enabled higher score in subjective image quality of artifacts (P < 0.05), whereas it showed no difference in the other subjective image-quality indices and image noise. Significant higher image noise and lower score of subjective image quality were observed in LD-FBP images (all P < 0.05).Both IMR and HIR improved image quality of low-dose chest CT by comparison of routine dose images reconstructed with FBP. Meanwhile, IMR allows further image quality improvement than HIR. PMID:27684818

  20. Rosai-Dorfman disease presenting as a breast mass and enlarged axillary lymph node mimicking malignancy: a case report and review of the literature.

    PubMed

    Tenny, Steven O; McGinness, Marilee; Zhang, Da; Damjanov, Ivan; Fan, Fang

    2011-01-01

    Rosai-Dorfman disease (also called sinus histiocytosis with massive lymphadenopathy) involves lymph nodes or lymph nodes with extranodal sites. We present a unique case of a patient presenting with a breast mass and axillary lymphadenopathy, mimicking malignancy clinically and radiographically. Core needle biopsies of the breast and axillary lymph node showed histologic features concerning the lymphoma. However, excisional biopsy specimen demonstrated characteristic features of Rosai-Dorfman disease. The disease recurred locally 6 months later in the same breast, 1 month later in the contralateral breast, and 11 month later in the subcutaneous tissue of left flank. A review of the literature of Rosai-Dorfman disease involving the breast is also presented. PMID:21762247

  1. Malignant hyperthermia.

    PubMed

    Brockhouse, R T

    1979-04-01

    A case has been presented that illustrates successful managment of a patient with suspected malignant hyperthermia. The causes of this disorder are uncertain. If screening procedures identify a patient as susceptible to this disorder, careful planning in the preoperative stage is indicated. Preparedness during the operative procedure for any emergency is mandatory. Early and effective treatment seems to be the only method of preventing mortality with patients experiencing malignant hyperthermia. PMID:285135

  2. Malignant oncocytoma.

    PubMed

    Laurian, N; Zohar, Y; Kende, L

    1977-09-01

    A case of malignant oncocytoma of the parotid gland in a 32-year-old male is presented. Ten months after parotidectomy an undifferentiated carcinoma, in which oncocytes still could be recognized, developed in the operated area. According to the literature available to us, this is the second reported case in which malignant transformation in a benign oncocytoma of the salivary gland has been observed.

  3. Hemostasis and malignancy.

    PubMed

    Francis, J L; Biggerstaff, J; Amirkhosravi, A

    1998-01-01

    There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors.

  4. Hemostasis and malignancy.

    PubMed

    Francis, J L; Biggerstaff, J; Amirkhosravi, A

    1998-01-01

    There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors. PMID:9579631

  5. Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

    ClinicalTrials.gov

    2016-07-20

    Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adenocarcinoma of Unknown Primary; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Duct Cell Adenocarcinoma of the Pancreas; Intestinal Adenocarcinoma of the Stomach; Localized Unresectable Adult Primary Liver Cancer; Metastatic Carcinoma of Unknown Primary; Metastatic Extrahepatic Bile Duct Cancer; Mixed Adenocarcinoma of the Stomach; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Newly Diagnosed Carcinoma of Unknown Primary; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Gallbladder Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Gallbladder Cancer; Stage IVB Rectal Cancer; Unresectable Extrahepatic Bile Duct Cancer

  6. Ibex-associated malignant catarrhal fever-like disease in a group of bongo antelope (Tragelaphus euryceros)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A private zoological facility experienced an outbreak of fatal malignant catarrhal fever (MCF) in a group of bongo antelope (Tragelaphus euryceros). Three periparturient female bongos exhibited an acute onset of anorexia beginning ~6 weeks after being housed with a Nubian ibex (Capra nubiana). Disea...

  7. Malignant Pleural Effusion Supernatants Are Substitutes for Metastatic Pleural Tumor Tissues in EGFR Mutation Test in Patients with Advanced Lung Adenocarcinoma

    PubMed Central

    Wu, Ning; Nie, Xiaomeng; Xia, Yang; Han, Yiping; Li, Qiang; Zhu, Guanshan; Bai, Chong

    2014-01-01

    Background Though the possibility of using malignant pleural effusions (MPEs) as alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth factor receptor (EGFR) mutation test has been examined, due to the lack of studies comparing the results in matching MPEs and MPTTs, the clinical value of MPEs for advanced adenocarcinoma patients with pleural effusions is not confirmed. Methods EGFR mutation statuses in matching MPTTs, MPE supernatants and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by thoracoscopy were analyzed using amplification refractory mutation system (ARMS). Results EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis. Generally, the same EGFR statuses were identified in both MPTTs and matching MPE cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19), specificity was 90.9% (20/22). Conclusions The high concordance of EGFR mutation statuses between MPEs and MPTTs in lung adenocarcinoma patients with pleural metastasis as determined by ARMS analysis suggests that MPEs, particularly MPE supernatants, may be substitutes for MPTTs in EGFR mutation test. PMID:24587142

  8. Na+ Micro-Current Value Detection as a New Modality for Identification of Benign and Malignant Disease in Surgery

    PubMed Central

    Zhang, Xu-Feng; Long, Zhi-Da; Liu, Xue-Min; Ma, Feng; Li, Qiang; Lv, Yi

    2016-01-01

    Increase of intracellular positive ions (mainly Na+) indicates greater possibility of cell malignancy. The present study investigated the correlation between the Na+ micro-current value (MCV) and tissue characteristics (normal, benign or malignant). 346 tissue samples have been detected within 30 min after surgical isolation by Na+ detector. MCV in 102 malignant tumor was significantly higher than that in benign/borderline tumor or normal tissue (33.3 ± 8.9 μA vs. 24.4 ± 8.6 μA and 14.0 ± 4.0 μA, p < 0.001, respectively). MCV in malignant tumor parenchyma was significantly higher than that in the paired paracanceroustissue, normal tissue and surgical margin tissue (33.3 ± 8.9 μA vs. 18.9 ± 4.1, 14.2 ± 4.0 or 15.2 ± 3.3, p < 0.001, respectively). However, the coincidence rate between Na+ detector and pathological examination was different in tissues from different organs or systems, which was high in pancreas, bile duct system, gastrointestinal system, esophagus, breasts, lungs, nose & throat and thyroids, but poor in urinary tissue. The overall coincidence rate was 83.1% (108/130) between Na+ detector and pathological examination. The sensitivity and specificity of correct diagnosis by Na+ detector was 83.3% (70/84) and 82.6% (38/46), respectively. This new modality may have diagnostic potential in complementing frozen examination in differentiating malignant tumor from benign or normal tissue, justifying tumor metastatic scope and confirming surgical margin. PMID:27103487

  9. Na(+) Micro-Current Value Detection as a New Modality for Identification of Benign and Malignant Disease in Surgery.

    PubMed

    Zhang, Xu-Feng; Long, Zhi-Da; Liu, Xue-Min; Ma, Feng; Li, Qiang; Lv, Yi

    2016-01-01

    Increase of intracellular positive ions (mainly Na(+)) indicates greater possibility of cell malignancy. The present study investigated the correlation between the Na(+) micro-current value (MCV) and tissue characteristics (normal, benign or malignant). 346 tissue samples have been detected within 30 min after surgical isolation by Na(+) detector. MCV in 102 malignant tumor was significantly higher than that in benign/borderline tumor or normal tissue (33.3 ± 8.9 μA vs. 24.4 ± 8.6 μA and 14.0 ± 4.0 μA, p < 0.001, respectively). MCV in malignant tumor parenchyma was significantly higher than that in the paired paracanceroustissue, normal tissue and surgical margin tissue (33.3 ± 8.9 μA vs. 18.9 ± 4.1, 14.2 ± 4.0 or 15.2 ± 3.3, p < 0.001, respectively). However, the coincidence rate between Na(+) detector and pathological examination was different in tissues from different organs or systems, which was high in pancreas, bile duct system, gastrointestinal system, esophagus, breasts, lungs, nose &throat and thyroids, but poor in urinary tissue. The overall coincidence rate was 83.1% (108/130) between Na(+) detector and pathological examination. The sensitivity and specificity of correct diagnosis by Na(+) detector was 83.3% (70/84) and 82.6% (38/46), respectively. This new modality may have diagnostic potential in complementing frozen examination in differentiating malignant tumor from benign or normal tissue, justifying tumor metastatic scope and confirming surgical margin. PMID:27103487

  10. Lessons from next-generation sequencing analysis in hematological malignancies

    PubMed Central

    Braggio, E; Egan, J B; Fonseca, R; Stewart, A K

    2013-01-01

    Next-generation sequencing has led to a revolution in the study of hematological malignancies with a substantial number of publications and discoveries in the last few years. Significant discoveries associated with disease diagnosis, risk stratification, clonal evolution and therapeutic intervention have been generated by this powerful technology. As part of the post-genomic era, sequencing analysis will likely become part of routine clinical testing and the challenge will ultimately be successfully transitioning from gene discovery to preventive and therapeutic intervention as part of individualized medicine strategies. In this report, we review recent advances in the understanding of hematological malignancies derived through genome-wide sequence analysis. PMID:23872706

  11. Use of high-intensity focused ultrasound in the treatment of both benign and malignant prostatic disease

    NASA Astrophysics Data System (ADS)

    Kernen, Kenneth M.; Miles, Brian J.

    2000-05-01

    Prostate cancer, the most common malignancy in men in the United States, accounts for more than 29% of all male cancers diagnosed and 13% of all cancer deaths. This translates into approximately 200,000 men diagnosed and 37,000 men who will die from the disease this year in this country. A significant number of patients ultimately choose external beam radiation or interstitial radioactive implants (brachytherapy) combined with external beam radiotherapy as their primary treatment. Approximately 25 - 35% of external beam irradiation patients and 20 - 30% of interstitial implants combined with external beam radiotherapy will fail within 10 years. The treatment options for patients with localized radiorecurrent disease include watchful waiting, endocrine therapy, salvage radiotherapy, and salvage radical prostatectomy, cryotherapy and now high intensity focused ultrasound therapy (HIFU). Although some studies regarding watchful waiting demonstrated comparable results to formal treatment for early prostate cancer, other studies have shown metastatic and mortality rates that are significantly higher, and that radiorecurrent patients would have even greater rates of metastasis and progression to death. Prostate cancer cure by means of endocrine therapy is highly unlikely and its role is still one of palliation with a side effect profile which includes hot flashes, osteoporosis, fatigue, loss of muscle mass, anemia, loss of libido and potency. The role of salvage radiotherapy may offer local control, however long term efficacy has yet to be determined. In a recent series, only 50% of the patients were controlled for a mean of four years with salvage radiotherapy. Salvage prostatectomy has the advantage of providing excellent local control and even a cure if the cancer is confined to the prostate or within the surrounding periprostatic tissue. Historically, salvage prostatectomy is technically demanding and fraught with higher complications. In one large series

  12. Drug nanocarrier, the future of atopic diseases: Advanced drug delivery systems and smart management of disease.

    PubMed

    Shao, Mei; Hussain, Zahid; Thu, Hnin Ei; Khan, Shahzeb; Katas, Haliza; Ahmed, Tarek A; Tripathy, Minaketan; Leng, Jing; Qin, Hua-Li; Bukhari, Syed Nasir Abbas

    2016-11-01

    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD.

  13. Drug nanocarrier, the future of atopic diseases: Advanced drug delivery systems and smart management of disease.

    PubMed

    Shao, Mei; Hussain, Zahid; Thu, Hnin Ei; Khan, Shahzeb; Katas, Haliza; Ahmed, Tarek A; Tripathy, Minaketan; Leng, Jing; Qin, Hua-Li; Bukhari, Syed Nasir Abbas

    2016-11-01

    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD. PMID:27592075

  14. Advances in imaging to allow personalized medicine in Crohn's disease.

    PubMed

    Neurath, Markus F

    2015-08-01

    Crohn's disease is a destructive inflammatory bowel disease of unknown origin that may lead to various complications such as strictures, stenosis, fistulas and colitis-associated neoplasias. However, the course of the disease varies substantially among patients and disease behaviour may also change with time. At diagnosis behaviour is inflammatory in the majority of patients, while penetrating or structuring behaviour become more prominent at later time points. Thus, medication in Crohn's disease needs frequent optimization over time. Therefore, new strategies for prediction of response to therapy are urgently needed. Here, recent advantages in imaging techniques for personalized medicine in Crohn's disease are reviewed. Such advantages include ultrasonography, computed tomography, magnetic resonance imaging and new endoscopic approaches such as molecular endoscopy. It is expected that these novel techniques will lead to marked improvements in the assessment of disease behaviour and the prediction of response to clinical therapy with biologicals. PMID:26002559

  15. "Malignant Cutaneous Ulcer".

    PubMed

    Sundriyal, Deepak; Kotwal, Sumedha

    2016-09-01

    Renal cell carcinoma (RCC) is an aggressive malignancy and the rich vascular supply enables it to metastasize early via haematogenous route. Skin lesions are a late manifestation of the disease. Clinicians should be aware of cutaneous presentation of RCC while evaluating a case of unknown primary with skin lesions. PMID:27651705

  16. Malignancies in systemic lupus erythematosus

    PubMed Central

    Kale, Mruganka; Ramsey-Goldman, Rosalind; Gordon, Caroline; Clarke, Ann E; Bernatsky, Sasha

    2013-01-01

    The purpose of this review is to underline important advancements in the understanding of cancer risks in systemic lupus erythematosus (SLE). In SLE, there is an increased risk of specific kinds of malignancy. For example, the risk of non-Hodgkin’s lymphoma is increased several-fold in SLE versus the general population. In addition, heightened risks for lung cancer, thyroid cancer and cervical dysplasia in SLE have been found. Some have postulated that immunosuppressive drugs play a role, as well as other important mediators, such as lupus disease activity itself. One new frontier being explored is the significant finding of a decreased risk of certain nonhematologic cancers (e.g., breast, ovarian, endometrial and prostate) in SLE. The reasons for this are currently under study. PMID:19643208

  17. Malignant pleural mesothelioma treated in Clinic for Pulmonary Diseases and Tuberculosis "Podhrastovi" in ten-year period (from 1998 to 2007).

    PubMed

    Cukić, Vesna; Ustamujić, Aida; Lovre, Vladimir; Zutić, Hasan; Genjac, Sadika; Masić-Zecević, Mina

    2008-11-01

    Malignant pleural mesothelioma (MPM) is the most common primary malign tumour of pleura. The aim of this study was to evaluate cases of MPM diagnosed and treated in Clinic for Pulmonary Diseases and Tuberculosis "Podhrastovi" during ten-year period (1998-2007). Study is retrospective. The patients were analysed according to age, sex, histopathologic type of the tumour, cantonal distribution in Federation of Bosnia and Herzegovina and regimen of treatment. MPM presented 0,72% (0-1,56% per year) of all hospitalised malignant patients, and the greatest number of registered cases was in the year of 2007. The series included 16 male (57,14%) and 12 female (42,86%). Cases over 64 years old were the most frequent (14-50%) than 45-54 years (7- not 25%). Histopathology types of hospitalised cases of MPM: epitheloid form (8- 28,57%); sarcomatoid form (2- 7,14 %); other forms (18-64,29%). The most patients came from Canton Sarajevo (12-42,86%); ZE-DO canton (8-28,57%) and the UNA-SANA canton (5-17,86%). The therapy applied: chemotherapy (11-39,29%); radiotherapy (3-10,71%); chemotherapy + radiotherapy (4-14,29%); symptomatic therapy (10-35,71 %).

  18. Malignant Transformation of Hepatic Adenoma in Glycogen Storage Disease Type-1a: Report of an Exceptional Case Diagnosed on Surveillance Imaging

    PubMed Central

    Baheti, Akshay D.; Yeh, Matthew M.; O'Malley, Ryan; Lalwani, Neeraj

    2015-01-01

    Hepatocellular adenoma is a heterogeneous group of benign neoplasms arising from hepatocellular cells and can be subclassified into four major groups based on genotypic and phenotypic characteristics. These four subtypes are hepatocyte nuclear factor (HNF) 1α-inactivated, β-catenin–activated, inflammatory, and unclassified adenomas. Immunohistochemistry studies have demonstrated that since β-catenin–activated adenomas have a higher risk of malignant transformation, the identification of the subtype of adenoma remains crucial in patient management. However, malignant transformation of hepatic adenoma without β-catenin overexpression can be seen in 30–65% cases. We report a case of malignant transformation of hepatic adenoma without overexpression of β-catenin in a 31-year-old man with a known glycogen storage disease (GSD) Type-1a, which was diagnosed on surveillance magnetic resonance imaging (MRI). The MRI showed a mild interval increase in one lesion with relative stability of the other adenomas. The lesion was presumed to be suspicious for a hepatocellular carcinoma (HCC) and was confirmed on pathology. PMID:26430540

  19. Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease.

    PubMed

    Egan, G; Cervone, K A; Philips, P C; Belasco, J B; Finlay, J L; Gardner, S L

    2016-04-01

    Recurrence of malignant brain tumors results in a poor prognosis with limited treatment options. High-dose chemotherapy with autologous hematopoietic cell rescue (AHCR) has been used in patients with recurrent malignant brain tumors and has shown improved outcomes compared with standard chemotherapy. Temozolomide is standard therapy for glioblastoma and has also shown activity in patients with medulloblastoma/primitive neuro-ectodermal tumor (PNET), particularly those with recurrent disease. Temozolomide was administered twice daily on days -10 to -6, followed by thiotepa 300 mg/m(2) per day and carboplatin dosed using the Calvert formula or body surface area on days -5 to -3, with AHCR day 0. Twenty-seven patients aged 3-46 years were enrolled. Diagnoses included high-grade glioma (n=12); medulloblastoma/PNET (n=9); central nervous system (CNS) germ cell tumor (n=4); ependymoma (n=1) and spinal cord PNET (n=1). Temozolomide doses ranged from 100 mg/m(2) per day to 400 mg/m(2) per day. There were no toxic deaths. Prolonged survival was noted in several patients including those with recurrent high-grade glioma, medulloblastoma and CNS germ cell tumor. Increased doses of temozolomide are feasible with AHCR. A phase II study using temozolomide, carboplatin and thiotepa with AHCR for children with recurrent malignant brain tumors is being conducted through the Pediatric Blood and Marrow Transplant Consortium. PMID:26726947

  20. Endorectal MRI of Prostate Cancer: Incremental Prognostic Importance of Gross Locally Advanced Disease

    PubMed Central

    Muglia, Valdair F.; Westphalen, Antonio C.; Wang, Zhen J.; Kurhanewicz, John; Carroll, Peter R.; Coakley, Fergus V.

    2013-01-01

    OBJECTIVE The purpose of this study was to determine the frequency and incremental prognostic importance of gross locally advanced disease seen at endorectal MRI in patients with prostate cancer. MATERIALS AND METHODS We retrospectively identified the cases of all patients with biopsy-proven prostate cancer who underwent pretreatment endorectal MRI over a 6-year period (n = 1777). Three experienced radiologists identified by consensus patients with gross locally advanced disease, defined as unequivocal extracapsular extension or unequivocal seminal vesicle invasion. Outcome among these patients was compared with that in a control group without gross locally advanced disease matched by D'Amico risk stratification. RESULTS Sixty-six of 1777 (3.7%) patients had gross locally advanced disease. One of 1085 (0.1%) patients had low-risk disease, 25 of 489 (5.1%) had intermediate-risk disease, and 40 of 203 (19.7%) had high-risk disease. Follow-up data were available for 44 of these 66 patients. During a median follow-up period of 79 months, biochemical failure and metastasis had developed in 17 and 6 of these 44 patients compared with 9 and none of the 65 patients in the control group (p < 0.001). CONCLUSION Almost 4% of patients with prostate cancer, particularly those with intermediate- and high-risk disease, have gross locally advanced disease at endorectal MRI and have a significantly worse prognosis than matched controls. These patients may be candidates for more aggressive treatment. PMID:22109291

  1. A phase I trial of the bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC3095 in patients with advanced solid malignancies.

    PubMed

    Schwartsmann, G; DiLeone, L P; Horowitz, M; Schunemann, D; Cancella, A; Pereira, A S; Richter, M; Souza, F; da Rocha, A Brondani; Souza, F H; Pohlmann, P; De Nucci, G

    2006-09-01

    Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumor models in vitro and in vivo. Animal toxicology studies showed no detectable organ toxicity apart from local irritation at the injection site. The purpose of this study was to determine the safety and feasibility of the administration of RC-3095 by daily subcutaneous injections in patients with advanced and refractory solid malignancies. Twenty-five patients received RC-3095 once or twice-daily at doses ranging from 8 to 96 ug/kg. Dose was escalated in groups of 3-5 patients per dose level. The only toxicity observed was local discomfort in the injection site at the highest doses. A single dose administration of RC-3095 at the highest dose level (96 ug/kg) was tested in a clearly hypergastrinemic individual with the Zollingen-Ellison syndrome and produced a decrease in plasma gastrin down to 50% of basal levels in 6 h. There was no objective tumor responses in patients included in the study. A short-lasting minor tumor response was observed in a patient with a GRP-expressing progressive medullary carcinoma of the thyroid. Due to problems with the analytical method, plasma pharmacokinetic data was obtained only from two patients included at the highest dose level. In these patients, RC-3095 reached plasma concentrations >100 ng/mL for about 8 h, which were within therapeutic levels on the basis of prior data obtained in mice and rats. The plasma elimination half-life was between 8.6-10.9 h. Due to the occurrence of local toxicity at the injection site, the dose escalation procedure could not be fully evaluated up to a maximum tolerated dose. Thus, a recommended dose of RC-3095 for Phase II trials could not be clearly established. Considering the

  2. Inherited CHST11/MIR3922 deletion is associated with a novel recessive syndrome presenting with skeletal malformation and malignant lymphoproliferative disease

    PubMed Central

    Chopra, Sameer S; Leshchiner, Ignaty; Duzkale, Hatice; McLaughlin, Heather; Giovanni, Monica; Zhang, Chengsheng; Stitziel, Nathan; Fingeroth, Joyce; Joyce, Robin M; Lebo, Matthew; Rehm, Heidi; Vuzman, Dana; Maas, Richard; Sunyaev, Shamil R; Murray, Michael; Cassa, Christopher A

    2015-01-01

    Glycosaminoglycans (GAGs) such as chondroitin are ubiquitous disaccharide carbohydrate chains that contribute to the formation and function of proteoglycans at the cell membrane and in the extracellular matrix. Although GAG-modifying enzymes are required for diverse cellular functions, the role of these proteins in human development and disease is less well understood. Here, we describe two sisters out of seven siblings affected by congenital limb malformation and malignant lymphoproliferative disease. Using Whole-Genome Sequencing (WGS), we identified in the proband deletion of a 55 kb region within chromosome 12q23 that encompasses part of CHST11 (encoding chondroitin-4-sulfotransferase 1) and an embedded microRNA (MIR3922). The deletion was homozygous in the proband but not in each of three unaffected siblings. Genotyping data from the 1000 Genomes Project suggest that deletions inclusive of both CHST11 and MIR3922 are rare events. Given that CHST11 deficiency causes severe chondrodysplasia in mice that is similar to human limb malformation, these results underscore the importance of chondroitin modification in normal skeletal development. Our findings also potentially reveal an unexpected role for CHST11 and/or MIR3922 as tumor suppressors whose disruption may contribute to malignant lymphoproliferative disease. PMID:26436107

  3. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson’s Disease

    PubMed Central

    Claassen, Daniel O.; Dobolyi, David G.; Isaacs, David A.; Roman, Olivia C.; Herb, Joshua; Wylie, Scott A.; Neimat, Joseph S.; Donahue, Manus J.; Hedera, Peter; Zald, David H.; Landman, Bennett A.; Bowman, Aaron B.; Dawant, Benoit M.; Rane, Swati

    2016-01-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson’s disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson’s Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2nd, or 3rd order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning. PMID:27330836

  4. Pleural malignancies.

    PubMed

    Vargas, F S; Teixeira, L R

    1996-07-01

    Carcinoma of the lung, metastatic breast carcinoma, and lymphoma are responsible for approximately 75% of all malignant pleural effusions. The presence of malignant cells in the pleural fluid or in the parietal pleura confirms the diagnosis. Recently, several authors have proposed the combination of morphometric procedures and quantitative analysis of nucleolar organizer regions stained by silver nitrate. Videothoracoscopy is recommended for patients suspected of having a malignant pleural effusion in whom the diagnosis is not established after two cytologic studies of the fluid and one needle biopsy. The standard treatment is the intrapleural instillation of a chemical agent to produce a pleurodesis. The recommended sclerosant is talc, a tetracycline derivative, or Corynebacterium parvum where it is available. When a patient is not an ideal candidate for chemical pleurodesis, the options include symptomatic treatment, serial thoracentesis, implantation of a pleuroperitoneal shunt, and pleurectomy. PMID:9363162

  5. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling.

    PubMed

    Escobar, Luis E; Craft, Meggan E

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks. PMID:27547199

  6. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling

    PubMed Central

    Escobar, Luis E.; Craft, Meggan E.

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks. PMID:27547199

  7. Advances and Limitations of Disease Biogeography Using Ecological Niche Modeling.

    PubMed

    Escobar, Luis E; Craft, Meggan E

    2016-01-01

    Mapping disease transmission risk is crucial in public and animal health for evidence based decision-making. Ecology and epidemiology are highly related disciplines that may contribute to improvements in mapping disease, which can be used to answer health related questions. Ecological niche modeling is increasingly used for understanding the biogeography of diseases in plants, animals, and humans. However, epidemiological applications of niche modeling approaches for disease mapping can fail to generate robust study designs, producing incomplete or incorrect inferences. This manuscript is an overview of the history and conceptual bases behind ecological niche modeling, specifically as applied to epidemiology and public health; it does not pretend to be an exhaustive and detailed description of ecological niche modeling literature and methods. Instead, this review includes selected state-of-the-science approaches and tools, providing a short guide to designing studies incorporating information on the type and quality of the input data (i.e., occurrences and environmental variables), identification and justification of the extent of the study area, and encourages users to explore and test diverse algorithms for more informed conclusions. We provide a friendly introduction to the field of disease biogeography presenting an updated guide for researchers looking to use ecological niche modeling for disease mapping. We anticipate that ecological niche modeling will soon be a critical tool for epidemiologists aiming to map disease transmission risk, forecast disease distribution under climate change scenarios, and identify landscape factors triggering outbreaks.

  8. Advancing the understanding of autism disease mechanisms through genetics

    PubMed Central

    de la Torre-Ubieta, Luis; Won, Hyejung; Stein, Jason L; Geschwind, Daniel H

    2016-01-01

    Progress in understanding the genetic etiology of autism spectrum disorders (ASD) has fueled remarkable advances in our understanding of its potential neurobiological mechanisms. Yet, at the same time, these findings highlight extraordinary causal diversity and complexity at many levels ranging from molecules to circuits and emphasize the gaps in our current knowledge. Here we review current understanding of the genetic architecture of ASD and integrate genetic evidence, neuropathology and studies in model systems with how they inform mechanistic models of ASD pathophysiology. Despite the challenges, these advances provide a solid foundation for the development of rational, targeted molecular therapies. PMID:27050589

  9. Advances in Raman spectroscopy for the diagnosis of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Sudworth, Caroline D.; Archer, John K. J.; Black, Richard A.; Mann, David

    2006-02-01

    Within the next 50 years Alzheimer's disease is expected to affect 100 million people worldwide. The progressive decline in the mental health of the patient is caused by severe brain atrophy generated by the breakdown and aggregation of proteins, resulting in β-amyloid plaques and neurofibrillary tangles. The greatest challenge to Alzheimer's disease lies in the pursuit of an early and definitive diagnosis, in order that suitable treatment can be administered. At the present time, definitive diagnosis is restricted to post-mortem examination. Alzheimer's disease also remains without a long-term cure. This research demonstrates the potential role of Raman spectroscopy, combined with principle components analysis (PCA), as a diagnostic method. Analyses of ethically approved ex vivo post-mortem brain tissues (originating from frontal and occipital lobes) from control (3 normal elderly subjects and 3 Huntingdon's disease subjects) and Alzheimer's disease (12 subjects) brain sections, and a further set of 12 blinded samples are presented. Spectra originating from these tissues are highly reproducible, and initial results indicate a vital difference in protein content and conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Further examination of these spectra using PCA allows for the separation of control from diseased tissues. The validation of the PCA models using blinded samples also displays promise for the identification of Alzheimer's disease, in conjunction with secondary information regarding other brain diseases and dementias. These results provide a route for Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

  10. Reaching Those Most in Need – A Call to Action for Advanced Parkinson’s Disease

    PubMed Central

    Agarwal, Shashank; Fleisher, Jori E

    2016-01-01

    Much of the clinical and research attention for Parkinson's Disease (PD) has focused on mild to moderate stages. As the disease advances, it can become difficult for patients to attend clinical visits. These patients are often lost to follow-up, and consequently, vanish from the pool of potential research subjects who could inform our management of this understudied population. We aim to increase awareness about this population and potential interventions to improve continuity of care and foster research in advanced PD.

  11. Malignancy-Associated Dyslipidemia

    PubMed Central

    Bielecka-Dąbrowa, Agata; Hannam, Simon; Rysz, Jacek; Banach, Maciej

    2011-01-01

    Cholesterol and triglycerides, important lipid constituents of cell, are essential to carry out several vital physiological functions. Lipids might be associated with cancers because they play a key role in the maintenance of cell integrity. The pathway for cholesterol synthesis may also produce various tumorigenic compounds and cholesterol serves as a precursor for the synthesis of many sex hormones linked to increased risk of various cancers. In some malignant diseases, blood cholesterol undergoes early and significant changes. The mechanism for the link between cancer and cholesterol remains controversial. The dates from studies are confusing because both hypolipidemia and hypercholesterolemia might be connected with malignancy. Not only cancers but also antineoplastic therapies have an influence on lipid profile. There are also dates suggesting that antihyperlipemic drugs might nfluenced malignancy. PMID:21660223

  12. Aspirin-exacerbated respiratory disease: pathophysiological insights and clinical advances

    PubMed Central

    Steinke, John W; Wilson, Jeff M

    2016-01-01

    Asthma and chronic rhinosinusitis are heterogeneous airway diseases of the lower and upper airways, respectively. Molecular and cellular studies indicate that these diseases can be categorized into unique endotypes, which have therapeutic implications. One such endotype is aspirin-exacerbated respiratory disease (AERD), which encompasses the triad of asthma, aspirin (or nonsteroidal anti-inflammatory drug) hypersensitivity, and nasal polyposis. AERD has unique pathophysiological features that distinguish it from aspirin-tolerant asthma and other forms of chronic rhinosinusitis. This review details molecular and cellular features of AERD and highlights current and future therapies that are based on these insights. PMID:27022293

  13. The benefit of consolidation radiotherapy to initial disease bulk in patients with advanced Hodgkin’s disease who achieved complete remission after standard chemotherapy

    PubMed Central

    Bayoumi, Yasser; Al-Homaidi, Abdulaziz; Zaidi, Syed; Tailor, Imran; Motiabi, Ibrahiem; Alshehri, Nawal; Al-Ghazali, Assem; Almudaibigh, Samer

    2015-01-01

    Background/purpose The aim of this study was to evaluate the role of consolidation radiotherapy (RT) in advanced-stage Hodgkin’s disease (HD) with initial bulky sites after radiological complete remission (CR) or partial response (PR) with positron emission tomography-negative (metabolic CR) following standard chemotherapy (ABVD [Adriamycin, bleomycin, vinblastine, and dacarbazine]) six to eight cycles. Patients and methods Adult patients with advanced-stage HD treated at our institute during the period 2006 to 2012 were retrospectively evaluated. One hundred and ninety-two patients with initial bulky disease size (>7 cm) who attained radiological CR/PR and metabolic CR were included in the analysis. One hundred and thirteen patients who received radiotherapy (RT) as consolidation postchemotherapy (RT group) were compared to 79 patients who did not receive RT (non-RT group). Disease-free (DFS) and overall survival (OS) rates were estimated using the Kaplan–Meier method and were compared according to treatment group by the log-rank tests at P ≤0.05 significance level. Results The mean age of the cohort was 33 (range: 14 to 81) years. Eighty-four patients received involved-field radiation and 29 patients received involved-site RT. The RT group had worse prognostic factors compared to the non-RT group. Thirteen (12%) relapses occurred in the RT group, and 19 (24%) relapses occurred in the non-RT group. Nine patients (8%) in the RT group died, compared to eleven patients (14%) in the non-RT group. Second malignancies were seen in only five patients: three patients in the RT group compared to two patients in the non-RT group. At 5 years, overall DFS was 79%±9% and OS was 85%±9%. There was significant statistical difference between the RT group and the non-RT group regarding 5-year DFS: 86%±7% and 74%±9%, respectively (P ≤0.02). However, the 5-year OS was 90%±5% for the RT group and 83%±8% for the non-RT group, with no statistical difference (P ≤0

  14. Malignant hypertension: a preventable emergency.

    PubMed

    van der Merwe, Walter; van der Merwe, Veronica

    2013-08-16

    The Waitemata Hypertension Clinic Database 2009-2012 (Auckland, New Zealand) was searched for patients meeting the definition of Malignant Hypertension. Eighteen of 565 patients met the criteria. All patients had essential hypertension which was either undiagnosed, untreated or undertreated. Most cases responded satisfactorily to standard drug therapy, but a number were left with significant chronic kidney disease. Malignant hypertension is a life-threatening disease which should be entirely preventable with regular blood pressure checks in primary care.

  15. Polycystic liver diseases: advanced insights into the molecular mechanisms.

    PubMed

    Perugorria, Maria J; Masyuk, Tatyana V; Marin, Jose J; Marzioni, Marco; Bujanda, Luis; LaRusso, Nicholas F; Banales, Jesus M

    2014-12-01

    Polycystic liver diseases are genetic disorders characterized by progressive bile duct dilatation and/or cyst development. The large volume of hepatic cysts causes different symptoms and complications such as abdominal distension, local pressure with back pain, hypertension, gastro-oesophageal reflux and dyspnea as well as bleeding, infection and rupture of the cysts. Current therapeutic strategies are based on surgical procedures and pharmacological management, which partially prevent or ameliorate the disease. However, as these treatments only show short-term and/or modest beneficial effects, liver transplantation is the only definitive therapy. Therefore, interest in understanding the molecular mechanisms involved in disease pathogenesis is increasing so that new targets for therapy can be identified. In this Review, the genetic mechanisms underlying polycystic liver diseases and the most relevant molecular pathways of hepatic cystogenesis are discussed. Moreover, the main clinical and preclinical studies are highlighted and future directions in basic as well as clinical research are indicated.

  16. [Advances on pharmacokinetics of traditional Chinese medicine under disease states].

    PubMed

    Gong, Zi-peng; Chen, Ying; Zhang, Rui-jie; Yang, Qing; Zhu, Xiao-xin

    2015-01-01

    In recent years, more and more research shows that the pharmacokinetic parameter of traditional Chinese medicine can be affected by the disease states. It's possible that drug metabolic enzymes, transporters, cell membrane permeability and the change of microbes group could be interfered with physiological and pathological changes, which enables the pharmacokinetics of traditional Chinese medicine in the body to be altered, including the process of absorption, distribution, metabolism and excretion, and then the pharmacokinetic parameters of traditional chinese medicine are altered. It's found that investigating the pharmacokinetic of traditional Chinese medicine in the pathological state is more useful than that of in normal state because the great part of traditional Chinese medicine is mainly used to treat disease. This article reflects the latest research on the pharmacokinetic of traditional Chinese medicine in the disease state such as diabete, cerebral ischemia, liver injury, inflammatory disease, nervous system disorders and fever in order to provide certain reference for clinicians designing reasonable administration dose.

  17. Advances in the Care of Adults With Congenital Heart Disease.

    PubMed

    Nasr, Viviane G; Kussman, Barry D

    2015-09-01

    The significant decline in mortality among children and adolescents with congenital heart disease (CHD) is associated with an increasing prevalence of CHD in adults, particularly those with moderate to severe defects. As a significant percentage of adolescents and young adults are lost to follow-up in the transition from pediatric to adult care, they may present for elective procedures with substantial CHD-associated morbidity. In addition to the specific cardiac defect, the procedures performed, and the current pathophysiological status, several factors should be considered when managing the adult with CHD. These include the type of setting (adult vs pediatric institution); surgeon (pediatric vs adult cardiac surgeon); coexisting diseases associated with CHD, such as coronary artery disease, hepatic dysfunction, renal dysfunction, cerebrovascular accidents, myopathy, and coagulation disorders; acquired diseases of aging; pregnancy; and psychosocial functioning. The current status of the management of common and important congenital cardiac defects is also described. PMID:25542866

  18. [Blood test for malignant lymphoma].

    PubMed

    Kobayashi, Tsutomu; Kuroda, Junya; Taniwaki, Masafumi

    2014-03-01

    Malignant lymphoma is a neoplastic disease that develops in the lymph system, which consists of various different subtypes. In addition, the differential diagnosis of malignant lymphoma includes infections, autoimmune diseases, allergic diseases, endocrine disorders, and so on. Therefore accurate diagnosis is very important to decide therapeutic strategy. Blood test is the most common examination in clinical practice and used extensively for evaluating etiology, pathology, disease state, efficacy of treatment and disease prognosis of lymphoma. We are required to understand the characteristics of blood examinations correctly and use them appropriately in daily medical practice. Here, we introduce some blood examinations used for treatment of lymphoma.

  19. Malignant hyperthermia.

    PubMed

    Taiclet, L

    1985-01-01

    Despite numerous reviews and clinical reports, much remains to be learned about the cause, treatment, and prevention of malignant hyperthermia.Among the most worrisome concerns of the clinician administering anesthesia is the malignant hyperthermia crisis. When it arises, it is always frightening-and sometimes fatal. Usually occurring very suddenly and without warning, malignant hyperthermia is considered to be a hypercatabolic crisis; the condition is known to affect humans and certain breeds of pigs. The exact triggering mechanisms of malignant hyperthermia (MH) in humans are not known, but a crisis can be initiated by volatile general anesthetics, neuromuscular blocking agents, and amide local anesthetics. Although a history of an MH crisis is a diagnostic aid, previous uneventful exposure to anesthesia does not guarantee the safety of the patient in subsequent anesthetic procedures.(1) For these reasons, it is important for the anesthesiologist to be aware of the initial signs of MH and to be prepared to provide immediate treatment to reverse such a crisis. PMID:3865561

  20. Malignant hyperthermia.

    PubMed Central

    Ben Abraham, R.; Adnet, P.; Glauber, V.; Perel, A.

    1998-01-01

    Malignant hyperthermia is a rare autosomal dominant trait that predisposes affected individuals to great danger when exposed to certain anaesthetic triggering agents (such as potent volatile anaesthetics and succinylcholine). A sudden hypermetabolic reaction in skeletal muscle leading to hyperthermia and massive rhabdomyolysis can occur. The ultimate treatment is dantrolene sodium a nonspecific muscle relaxant. Certain precautions should be taken before anaesthesia of patients known to be susceptible to malignant hyperthermia. These include the prohibition of the use of triggering agents, monitoring of central body temperature and expired CO2, and immediate availability of dantrolene. In addition, careful cleansing of the anaesthesia machine of vapours of halogenated agents is recommended. If these measures are taken, the chances of an MH episode are greatly reduced. When malignant hyperthermia-does occur in the operating room, prompt recognition and treatment usually prevent a potentially fatal outcome. The most reliable test to establish susceptibility to malignant hyperthermia is currently the in vitro caffeine-halothane contracture test. It is hoped that in the future a genetic test will be available. PMID:9538480

  1. Nuclear magnetic resonance based metabolomics and liver diseases: Recent advances and future clinical applications.

    PubMed

    Amathieu, Roland; Triba, Mohamed Nawfal; Goossens, Corentine; Bouchemal, Nadia; Nahon, Pierre; Savarin, Philippe; Le Moyec, Laurence

    2016-01-01

    Metabolomics is defined as the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification. It is an "omics" technique that is situated downstream of genomics, transcriptomics and proteomics. Metabolomics is recognized as a promising technique in the field of systems biology for the evaluation of global metabolic changes. During the last decade, metabolomics approaches have become widely used in the study of liver diseases for the detection of early biomarkers and altered metabolic pathways. It is a powerful technique to improve our pathophysiological knowledge of various liver diseases. It can be a useful tool to help clinicians in the diagnostic process especially to distinguish malignant and non-malignant liver disease as well as to determine the etiology or severity of the liver disease. It can also assess therapeutic response or predict drug induced liver injury. Nevertheless, the usefulness of metabolomics is often not understood by clinicians, especially the concept of metabolomics profiling or fingerprinting. In the present work, after a concise description of the different techniques and processes used in metabolomics, we will review the main research on this subject by focusing specifically on in vitro proton nuclear magnetic resonance spectroscopy based metabolomics approaches in human studies. We will first consider the clinical point of view enlighten physicians on this new approach and emphasis its future use in clinical "routine".

  2. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management

    PubMed Central

    Mirrakhimov, Aibek E.

    2015-01-01

    Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy including parathyroid hormone-related peptide-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25 Vitamin D-mediated hypercalcemia, and parathyroid hormone-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers. Diagnosis should include the history and physical examination as well as measurement of the above mediators of hypercalcemia. Management includes hydration, calcitonin, bisphosphonates, denosumab, and in certain patients, prednisone and cinacalcet. Patients with advanced underlying kidney disease and refractory severe hypercalcemia should be considered for hemodialysis. Hematology or oncology and palliative care specialists should be involved early to guide the options of cancer targeted therapies and help the patients and their closed ones with the discussion of comfort-oriented care. PMID:26713296

  3. Solitary intracranial tuberculoma mimicking a malignant tumor in a patient without tubercular lesions or a history of disease: a case report

    PubMed Central

    Bustamante-Rengifo, Javier A.; Sua, Luz F.; Astudillo, Miryam; Bravo, Luis E.

    2013-01-01

    Cerebral tuberculoma is a rare cause of intracranial mass. In Latin America and Colombia where tuberculosis is endemic, it represents between 5 and 30% of brain tumours. A 53-year-old Colombian woman was admitted to a third-level hospital in Cali, Colombia, after reporting loss of consciousness, headache, paresthesia, and flight of ideas for a two-week period. Imaging studies showed a left frontal mass of malignant appearance whose first possible diagnosis was metastatic neoplasia or glioma. With the initial results, absence of history of chronic infectious diseases and a history of thyroidectomy, a surgical procedure was carried out and a histopathological and molecular evaluation was conducted. The pathology report noted necrotizing granulomatous inflammation and tissue staining and molecular tests for detection of M. tuberculosis were positive and the patient was managed with anti-tubercular treatment. Intracranial masses are frequently targeted as a malignant neoplastic disease for surgical treatment. Considering an infectious etiology must be a diagnostic option. PMID:23725511

  4. Partially erupted third molars as a potential source of infection in patients receiving peripheral stem cell transplantation for malignant diseases: a retrospective study.

    PubMed

    Ohman, David; Björk, Yvonne; Bratel, John; Kristiansson, Camilla; Johansson, Peter; Johansson, Jan-Erik; Brune, Mats; Hasséus, Bengt

    2010-02-01

    Forty-four patients with malignant diseases for which they received peripheral stem cell transplant therapy (PSCT) were retrospectively studied regarding local and systemic infection originating from around partially erupted third molars (PEMs). Twenty-two patients had one or more PEMs, while 22 patients had none. Data were retrieved from medical and dental records. Systemic and local signs of infection and treatment were assessed. We recorded the number of transplanted CD34(+) blood stem cells, days with white blood cell counts < 0.5 x 10(9) l(-1), days until engraftment, maximum level of C-reactive protein (CRP), days with fever, positive blood cultures, days taking antibiotics, days drinking < 0.5 l, days of total parenteral nutrition, days receiving intravenously administered analgesics, and number of admission days. No statistically significant difference was detected between patients with PEMs and those without PEMs regarding any of the studied parameters. Of patients with PEMs, 36% (8 of 22) developed local infections around PEMs during the PSCT period. The study indicates that PEMs pose no significant risk of causing systemic infection in patients receiving PSCT for malignant diseases but increase the risk of developing a local infection, justifying close supervision and early treatment in cases of local infection during PSCT treatment. PMID:20156265

  5. Use of high-intensity focused ultrasound in the treatment of both benign and malignant prostatic disease

    NASA Astrophysics Data System (ADS)

    Kernen, Kenneth M.; Miles, Brian J.

    2000-05-01

    Prostate cancer, the most common malignancy in men in the United States, accounts for more than 29% of all male cancers diagnosed and 13% of all cancer deaths. This translates into approximately 200,000 men diagnosed and 37,000 men who will die from the disease this year in this country. A significant number of patients ultimately choose external beam radiation or interstitial radioactive implants (brachytherapy) combined with external beam radiotherapy as their primary treatment. Approximately 25 - 35% of external beam irradiation patients and 20 - 30% of interstitial implants combined with external beam radiotherapy will fail within 10 years. The treatment options for patients with localized radiorecurrent disease include watchful waiting, endocrine therapy, salvage radiotherapy, and salvage radical prostatectomy, cryotherapy and now high intensity focused ultrasound therapy (HIFU). Although some studies regarding watchful waiting demonstrated comparable results to formal treatment for early prostate cancer, other studies have shown metastatic and mortality rates that are significantly higher, and that radiorecurrent patients would have even greater rates of metastasis and progression to death. Prostate cancer cure by means of endocrine therapy is highly unlikely and its role is still one of palliation with a side effect profile which includes hot flashes, osteoporosis, fatigue, loss of muscle mass, anemia, loss of libido and potency. The role of salvage radiotherapy may offer local control, however long term efficacy has yet to be determined. In a recent series, only 50% of the patients were controlled for a mean of four years with salvage radiotherapy. Salvage prostatectomy has the advantage of providing excellent local control and even a cure if the cancer is confined to the prostate or within the surrounding periprostatic tissue. Historically, salvage prostatectomy is technically demanding and fraught with higher complications. In one large series

  6. Surveillance for gastrointestinal malignancies

    PubMed Central

    Tiwari, Ashish K; Laird-Fick, Heather S; Wali, Ramesh K; Roy, Hemant K

    2012-01-01

    Gastrointestinal (GI) malignancies are notorious for frequently progressing to advanced stages even in the absence of serious symptoms, thus leading to delayed diagnoses and dismal prognoses. Secondary prevention of GI malignancies through early detection and treatment of cancer-precursor/premalignant lesions, therefore, is recognized as an effective cancer prevention strategy. In order to efficiently detect these lesions, systemic application of screening tests (surveillance) is needed. However, most of the currently used non-invasive screening tests for GI malignancies (for example, serum markers such as alpha-fetoprotein for hepatocellular carcinoma, and fecal occult blood test, for colon cancer) are only modestly effective necessitating the use of highly invasive endoscopy-based procedures, such as esophagogastroduodenoscopy and colonoscopy for screening purposes. Even for hepatocellular carcinoma where non-invasive imaging (ultrasonography) has become a standard screening tool, the need for repeated liver biopsies of suspicious liver nodules for histopathological confirmation can’t be avoided. The invasive nature and high-cost associated with these screening tools hinders implementation of GI cancer screening programs. Moreover, only a small fraction of general population is truly predisposed to developing GI malignancies, and indeed needs surveillance. To spare the average-risk individuals from superfluous invasive procedures and achieve an economically viable model of cancer prevention, it’s important to identify cohorts in general population that are at substantially high risk of developing GI malignancies (risk-stratification), and select suitable screening tests for surveillance in these cohorts. We herein provide a brief overview of such high-risk cohorts for different GI malignancies, and the screening strategies that have commonly been employed for surveillance purpose in them. PMID:22969223

  7. Advances and Challenges in Genomic Selection for Disease Resistance.

    PubMed

    Poland, Jesse; Rutkoski, Jessica

    2016-08-01

    Breeding for disease resistance is a central focus of plant breeding programs, as any successful variety must have the complete package of high yield, disease resistance, agronomic performance, and end-use quality. With the need to accelerate the development of improved varieties, genomics-assisted breeding is becoming an important tool in breeding programs. With marker-assisted selection, there has been success in breeding for disease resistance; however, much of this work and research has focused on identifying, mapping, and selecting for major resistance genes that tend to be highly effective but vulnerable to breakdown with rapid changes in pathogen races. In contrast, breeding for minor-gene quantitative resistance tends to produce more durable varieties but is a more challenging breeding objective. As the genetic architecture of resistance shifts from single major R genes to a diffused architecture of many minor genes, the best approach for molecular breeding will shift from marker-assisted selection to genomic selection. Genomics-assisted breeding for quantitative resistance will therefore necessitate whole-genome prediction models and selection methodology as implemented for classical complex traits such as yield. Here, we examine multiple case studies testing whole-genome prediction models and genomic selection for disease resistance. In general, whole-genome models for disease resistance can produce prediction accuracy suitable for application in breeding. These models also largely outperform multiple linear regression as would be applied in marker-assisted selection. With the implementation of genomic selection for yield and other agronomic traits, whole-genome marker profiles will be available for the entire set of breeding lines, enabling genomic selection for disease at no additional direct cost. In this context, the scope of implementing genomics selection for disease resistance, and specifically for quantitative resistance and quarantined pathogens

  8. Advances and Challenges in Genomic Selection for Disease Resistance.

    PubMed

    Poland, Jesse; Rutkoski, Jessica

    2016-08-01

    Breeding for disease resistance is a central focus of plant breeding programs, as any successful variety must have the complete package of high yield, disease resistance, agronomic performance, and end-use quality. With the need to accelerate the development of improved varieties, genomics-assisted breeding is becoming an important tool in breeding programs. With marker-assisted selection, there has been success in breeding for disease resistance; however, much of this work and research has focused on identifying, mapping, and selecting for major resistance genes that tend to be highly effective but vulnerable to breakdown with rapid changes in pathogen races. In contrast, breeding for minor-gene quantitative resistance tends to produce more durable varieties but is a more challenging breeding objective. As the genetic architecture of resistance shifts from single major R genes to a diffused architecture of many minor genes, the best approach for molecular breeding will shift from marker-assisted selection to genomic selection. Genomics-assisted breeding for quantitative resistance will therefore necessitate whole-genome prediction models and selection methodology as implemented for classical complex traits such as yield. Here, we examine multiple case studies testing whole-genome prediction models and genomic selection for disease resistance. In general, whole-genome models for disease resistance can produce prediction accuracy suitable for application in breeding. These models also largely outperform multiple linear regression as would be applied in marker-assisted selection. With the implementation of genomic selection for yield and other agronomic traits, whole-genome marker profiles will be available for the entire set of breeding lines, enabling genomic selection for disease at no additional direct cost. In this context, the scope of implementing genomics selection for disease resistance, and specifically for quantitative resistance and quarantined pathogens

  9. Intrapleural therapy of malignant pleurisy in patients with neuroblastoma.

    PubMed

    Ha, K; Tawa, A; Ikeda, T; Tanaka, J; Okada, A; Yabuuchi, H

    1981-01-01

    Three children with advanced neuroblastoma developed pleural effusion in the course of their disease. This unusual complication was successfully treated with intrapleural administration of a nonspecific "immunostimulatory" agent; cell wall skeleton of Nocardia rubra (N-cws). The side effects of this procedure were mild and well tolerated even in infants in spite of their terminal stage. Intrapleural therapy in this study seemed to be useful for the treatment of pediatric malignant pleurisy.

  10. The role of estrogen receptor {beta} (ER{beta}) in malignant diseases-A new potential target for antiproliferative drugs in prevention and treatment of cancer

    SciTech Connect

    Warner, Margaret; Gustafsson, Jan-Ake

    2010-05-21

    The discovery of ER{beta} in the middle of the 1990s represents a paradigm shift in our understanding of estrogen signaling. It has turned out that estrogen action is not mediated by one receptor, ER{alpha}, but by two balancing factors, ER{alpha} and ER{beta}, which are often antagonistic to one another. Excitingly, ER{beta} has been shown to be widespread in the body and to be involved in a multitude of physiological and pathophysiological events. This has led to a strong interest of the pharmaceutical industry to target ER{beta} by drugs against various diseases. In this review, focus is on the role of ER{beta} in malignant diseases where the anti proliferative activity of ER{beta} gives hope of new therapeutic approaches.

  11. Advances in the Urinary Exosomes in Renal Diseases.

    PubMed

    Chen, Pei-Pei; Qin, Yan; Li, Xue-Mei

    2016-08-01

    Cells secrete around 30-100 nm membrane-enclosed vesicles that are released into the extracellular spaceis termed exosomes(EXs). EXs widely present in body fluids and incorporated proteins,nucleic acids that reflect the physiological state of their cells of origin and they may play an important role in cell-to-cell communication in various physiological and disease processes. In this article we review the recent basic and clinical studies in urinary EXs in renal diseases,focusing on their biological characteristics and potential roles as new biological markers,intervention treatment goals,and targeted therapy vectors in renal diseases.However,some issues still exist;in particular,the clinical application of EXs as a liquid biopsy technique warrants further investigations. PMID:27594162

  12. Advances in nutritional therapy in inflammatory bowel diseases: Review

    PubMed Central

    Wędrychowicz, Andrzej; Zając, Andrzej; Tomasik, Przemysław

    2016-01-01

    Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted. PMID:26811646

  13. Drug-eluting stent in malignant biliary obstruction

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Ki; Jang, Sung Ill

    2012-10-01

    Endoscopic stent insertion is the treatment of choice for patients with malignant biliary obstruction. However, conventional stents enable only mechanical palliation of the obstruction, without any anti-tumor effects. Drugeluting stent (DES), which was first introduced in coronary artery disease, are currently under investigation for sustaining stent patency and prolonging patient survival by inhibiting tumor ingrowth in malignant biliary obstruction. Many factors affecting efficient drug delivery have been studied to determine how drugs with antitumor effects suppress tumor ingrowth, including the specific drugs incorporated, means of incorporating the drugs, mode of drug release, and stent structure. Advances have resulted in the construction of more effective non-vascular DES and ongoing clinical research. Non-vascular DES is expected to play a vital role in prolonging the survival of patients with malignant biliary obstruction.

  14. Non-coding RNA repertoires in malignant pleural mesothelioma.

    PubMed

    Quinn, Leah; Finn, Stephen P; Cuffe, Sinead; Gray, Steven G

    2015-12-01

    Malignant pleural mesothelioma (MPM) is a rare malignancy, with extremely poor survival rates. There are limited treatment options, with no second line standard of care for those who fail first line chemotherapy. Recent advances have been made to characterise the underlying molecular mechanisms of mesothelioma, in the hope of providing new targets for therapy. With the discovery that non-coding regions of our DNA are more than mere junk, the field of research into non-coding RNAs (ncRNAs) has exploded in recent years. Non-coding RNAs have diverse and important roles in a variety of cellular processes, but are also implicated in malignancy. In the following review, we discuss two types of non-coding RNAs, long non-coding RNAs and microRNAs, in terms of their role in the pathogenesis of MPM and their potential as both biomarkers and as therapeutic targets in this disease. PMID:26791801

  15. Non-coding RNA repertoires in malignant pleural mesothelioma.

    PubMed

    Quinn, Leah; Finn, Stephen P; Cuffe, Sinead; Gray, Steven G

    2015-12-01

    Malignant pleural mesothelioma (MPM) is a rare malignancy, with extremely poor survival rates. There are limited treatment options, with no second line standard of care for those who fail first line chemotherapy. Recent advances have been made to characterise the underlying molecular mechanisms of mesothelioma, in the hope of providing new targets for therapy. With the discovery that non-coding regions of our DNA are more than mere junk, the field of research into non-coding RNAs (ncRNAs) has exploded in recent years. Non-coding RNAs have diverse and important roles in a variety of cellular processes, but are also implicated in malignancy. In the following review, we discuss two types of non-coding RNAs, long non-coding RNAs and microRNAs, in terms of their role in the pathogenesis of MPM and their potential as both biomarkers and as therapeutic targets in this disease.

  16. A Phase I Study of the First-in-Class Anti-Mitochondrial Metabolism Agent, CPI-613, in Patients with Advanced Hematologic Malignancies

    PubMed Central

    Pardee, Timothy S.; Lee, King; Luddy, John; Maturo, Claudia; Rodriguez, Robert; Isom, Scott; Miller, Lance D.; Stadelman, Kristin M.; Levitan, Denise; Hurd, David; Ellis, Leslie R.; Harrelson, Robin; Manuel, Megan; Dralle, Sarah; Lyerly, Susan; Powell, Bayard L

    2014-01-01

    Purpose The lipoate derivative CPI-613 is a first-in-class agent that targets mitochondrial metabolism. This study determined the effects of CPI-613 on mitochondrial function and defined the maximally tolerated dose (MTD), pharmacokinetics (PKs), and safety in patients with relapsed or refractory hematologic malignancies. Experimental Design Human leukemia cell lines were exposed to CPI-613 and mitochondrial function was assayed. A phase I trial was conducted in which CPI-613 was given as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days. Results CPI-613 inhibited mitochondrial respiration of human leukemia cells consistent with the proposed mechanism of action. In the phase I trial, 26 patients were enrolled. CPI-613 was well tolerated with no marrow suppression observed. When the infusion time was shortened to 1 hour renal failure occurred in 2 patients. At 3780 mg/m2, there were 2 dose-limiting toxicities (DLTs). At a dose of 2940 mg/m2 over 2 hours, no DLTs were observed, establishing this as the MTD. Renal failure occurred in a total of 4 patients and resolved in all but 1, who chose hospice care. CPI-613 has a triphasic elimination with an alpha half-life of ~1.34 hours. Of 21 evaluable, heavily pretreated, patients, 4 achieved an objective response and 2 achieved prolonged stabilization of disease for a clinical benefit rate of 29%. Following drug exposure, gene expression profiles of peripheral blood mononuclear cells from responders demonstrated immune activation. Conclusion CPI-613 inhibits mitochondrial function and demonstrates activity in a heavily pretreated cohort of patients. PMID:25165100

  17. Recent advances in the cell biology of polycystic kidney disease.

    PubMed

    Smyth, Brendan J; Snyder, Richard W; Balkovetz, Daniel F; Lipschutz, Joshua H

    2003-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a significant familial disorder, crossing multiple ethnicities as well as organ systems. The goal of understanding and, ultimately, curing ADPKD has fostered collaborative efforts among many laboratories, mustered on by the opportunity to probe fundamental cellular biology. Here we review what is known about ADPKD including well-accepted data such as the identification of the causative genes and the fact that PKD1 and PKD2 act in the same pathway, fairly well-accepted concepts such as the "two-hit hypothesis," and somewhat confusing information regarding polycystin-1 and -2 localization and protein interactions. Special attention is paid to the recently discovered role of the cilium in polycystic kidney disease and the model it suggests. Studying ADPKD is important, not only as an evaluation of a multisystem disorder that spans a lifetime, but as a testament to the achievements of modern biology and medicine.

  18. New advances on glial activation in health and disease

    PubMed Central

    Lee, Kim Mai; MacLean, Andrew G

    2015-01-01

    In addition to being the support cells of the central nervous system (CNS), astrocytes are now recognized as active players in the regulation of synaptic function, neural repair, and CNS immunity. Astrocytes are among the most structurally complex cells in the brain, and activation of these cells has been shown in a wide spectrum of CNS injuries and diseases. Over the past decade, research has begun to elucidate the role of astrocyte activation and changes in astrocyte morphology in the progression of neural pathologies, which has led to glial-specific interventions for drug development. Future therapies for CNS infection, injury, and neurodegenerative disease are now aimed at targeting astrocyte responses to such insults including astrocyte activation, astrogliosis and other morphological changes, and innate and adaptive immune responses. PMID:25964871

  19. Conventional and advanced MR imaging in infantile Refsum disease.

    PubMed

    Kılıç, Mustafa; Karlı-Oğuz, Kader; Haliloğlu, Göknur; Topçu, Meral; Wanders, Ronald James; Coşkun, Turgay

    2015-01-01

    We report magnetic resonance (MR) imaging findings including diffusion-weighted imaging and proton MR spectroscopy findings in a patient with infantile Refsum disease. The initial diagnosis was made on the basis of history, clinical findings and biochemical studies. Bilateral and symmetrical involvement of the peritrigonal white matter, centrum semiovale, thalami, corpus callosum and corticospinal tracts as assessed by increased T2 signal was highly suggestive of a peroxisomal disorder. Facilitated diffusion was observed in diseased parenchyma. Long echo-time (TE: 270 ms) MRS showed decreased N-acetyl-aspartate/creatine and elevated choline/creatine and lactate; short echo-time MRS (TE: 30 ms) revealed increased myoinositol at 3.56 ppm and lipid peaks at 0.9 and 1.3 ppm. A major contribution to the differential diagnosis came from MR imaging and proton MRS, as discussed in this report.

  20. Advances in pediatrics in 2014: current practices and challenges in allergy, gastroenterology, infectious diseases, neonatology, nutrition, oncology and respiratory tract illnesses.

    PubMed

    Caffarelli, Carlo; Santamaria, Francesca; Cesari, Silvia; Sciorio, Elisa; Povesi-Dascola, Carlotta; Bernasconi, Sergio

    2015-01-01

    Major advances in the conduct of pediatric practice have been reported in the Italian Journal of Pediatrics in 2014. This review highlights developments in allergy, gastroenterology, infectious diseases, neonatology, nutrition, oncology and respiratory tract illnesses. Investigations endorse a need to better educate guardians and improve nutritional management in food allergy. Management of hyperbilirubinemia in neonates and of bronchiolitis have been improved by position statements of scientific societies. Novel treatments for infant colic and inflammatory bowel diseases have emerged. Studies suggest the diagnostic utility of ultrasonography in diagnosing community-acquired pneumonia. Progress in infectious diseases should include the universal varicella vaccination of children. Recommendations on asphyxia and respiratory distress syndrome have been highlighted in neonatology. Studies have evidenced that malnutrition remains a common underestimated problem in developing countries, while exposure to cancer risk factors in children is not negligible in Western countries. Advances in our understanding of less common diseases such as cystic fibrosis, plastic bronchitis, idiopathic pulmonary hemosiderosis facilitate diagnosis and management. Researches have led to new therapeutic approaches in patent ductus arteriosus and pediatric malignancies.

  1. Why musical memory can be preserved in advanced Alzheimer's disease.

    PubMed

    Jacobsen, Jörn-Henrik; Stelzer, Johannes; Fritz, Thomas Hans; Chételat, Gael; La Joie, Renaud; Turner, Robert

    2015-08-01

    Musical memory is considered to be partly independent from other memory systems. In Alzheimer's disease and different types of dementia, musical memory is surprisingly robust, and likewise for brain lesions affecting other kinds of memory. However, the mechanisms and neural substrates of musical memory remain poorly understood. In a group of 32 normal young human subjects (16 male and 16 female, mean age of 28.0 ± 2.2 years), we performed a 7 T functional magnetic resonance imaging study of brain responses to music excerpts that were unknown, recently known (heard an hour before scanning), and long-known. We used multivariate pattern classification to identify brain regions that encode long-term musical memory. The results showed a crucial role for the caudal anterior cingulate and the ventral pre-supplementary motor area in the neural encoding of long-known as compared with recently known and unknown music. In the second part of the study, we analysed data of three essential Alzheimer's disease biomarkers in a region of interest derived from our musical memory findings (caudal anterior cingulate cortex and ventral pre-supplementary motor area) in 20 patients with Alzheimer's disease (10 male and 10 female, mean age of 68.9 ± 9.0 years) and 34 healthy control subjects (14 male and 20 female, mean age of 68.1 ± 7.2 years). Interestingly, the regions identified to encode musical memory corresponded to areas that showed substantially minimal cortical atrophy (as measured with magnetic resonance imaging), and minimal disruption of glucose-metabolism (as measured with (18)F-fluorodeoxyglucose positron emission tomography), as compared to the rest of the brain. However, amyloid-β deposition (as measured with (18)F-flobetapir positron emission tomography) within the currently observed regions of interest was not substantially less than in the rest of the brain, which suggests that the regions of interest were still in a very early stage of the expected course of

  2. Advances in chest drain management in thoracic disease.

    PubMed

    George, Robert S; Papagiannopoulos, Kostas

    2016-02-01

    An adequate chest drainage system aims to drain fluid and air and restore the negative pleural pressure facilitating lung expansion. In thoracic surgery the post-operative use of the conventional underwater seal chest drainage system fulfills these requirements, however they allow great variability amongst practices. In addition they do not offer accurate data and they are often inconvenient to both patients and hospital staff. This article aims to simplify the myths surrounding the management of chest drains following chest surgery, review current experience and explore the advantages of modern digital chest drain systems and address their disease-specific use. PMID:26941971

  3. Advances in chest drain management in thoracic disease.

    PubMed

    George, Robert S; Papagiannopoulos, Kostas

    2016-02-01

    An adequate chest drainage system aims to drain fluid and air and restore the negative pleural pressure facilitating lung expansion. In thoracic surgery the post-operative use of the conventional underwater seal chest drainage system fulfills these requirements, however they allow great variability amongst practices. In addition they do not offer accurate data and they are often inconvenient to both patients and hospital staff. This article aims to simplify the myths surrounding the management of chest drains following chest surgery, review current experience and explore the advantages of modern digital chest drain systems and address their disease-specific use.

  4. Advance in the pathogenesis and treatment of Wilson disease

    PubMed Central

    2012-01-01

    Wilson disease is an autosomal recessive disorder of copper metabolism. Diagnosis depends primarily on clinical features, biochemical parameters and the presence of the Kayser-Fleischer ring. Genetic analysis for mutations within ATP7B is a convincing diagnostic tool. The traditional treatment for WD includes chelation of excessive copper accumulation and reduction of copper intake. Medical therapy is effective but WD is not yet curable. Liver transplantation is especially helpful for patients who fail to respond to medical therapy or present with fulminant liver failure, although evaluation of its long-term effect are still in need. PMID:23210912

  5. Advances in metal-induced oxidative stress and human disease.

    PubMed

    Jomova, Klaudia; Valko, Marian

    2011-05-10

    Detailed studies in the past two decades have shown that redox active metals like iron (Fe), copper (Cu), chromium (Cr), cobalt (Co) and other metals undergo redox cycling reactions and possess the ability to produce reactive radicals such as superoxide anion radical and nitric oxide in biological systems. Disruption of metal ion homeostasis may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently induces DNA damage, lipid peroxidation, protein modification and other effects, all symptomatic for numerous diseases, involving cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's disease, Parkinson's disease), chronic inflammation and others. The underlying mechanism of action for all these metals involves formation of the superoxide radical, hydroxyl radical (mainly via Fenton reaction) and other ROS, finally producing mutagenic and carcinogenic malondialdehyde (MDA), 4-hydroxynonenal (HNE) and other exocyclic DNA adducts. On the other hand, the redox inactive metals, such as cadmium (Cd), arsenic (As) and lead (Pb) show their toxic effects via bonding to sulphydryl groups of proteins and depletion of glutathione. Interestingly, for arsenic an alternative mechanism of action based on the formation of hydrogen peroxide under physiological conditions has been proposed. A special position among metals is occupied by the redox inert metal zinc (Zn). Zn is an essential component of numerous proteins involved in the defense against oxidative stress. It has been shown, that depletion of Zn may enhance DNA damage via impairments of DNA repair mechanisms. In addition, Zn has an impact on the immune system and possesses neuroprotective properties. The mechanism of metal-induced formation of free radicals is tightly influenced by the action of cellular antioxidants. Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha

  6. Advances in Gene Therapy for Diseases of the Eye

    PubMed Central

    Petit, Lolita; Khanna, Hemant; Punzo, Claudio

    2016-01-01

    Over the last few years, huge progress has been made with regard to the understanding of molecular mechanisms underlying the pathogenesis of neurodegenerative diseases of the eye. Such knowledge has led to the development of gene therapy approaches to treat these devastating disorders. Challenges regarding the efficacy and efficiency of therapeutic gene delivery have driven the development of novel therapeutic approaches, which continue to evolve the field of ocular gene therapy. In this review article, we will discuss the evolution of preclinical and clinical strategies that have improved gene therapy in the eye, showing that treatment of vision loss has a bright future. PMID:27178388

  7. Advances in Gene Therapy for Diseases of the Eye.

    PubMed

    Petit, Lolita; Khanna, Hemant; Punzo, Claudio

    2016-08-01

    Over the last few years, huge progress has been made with regard to the understanding of molecular mechanisms underlying the pathogenesis of neurodegenerative diseases of the eye. Such knowledge has led to the development of gene therapy approaches to treat these devastating disorders. Challenges regarding the efficacy and efficiency of therapeutic gene delivery have driven the development of novel therapeutic approaches, which continue to evolve the field of ocular gene therapy. In this review article, we will discuss the evolution of preclinical and clinical strategies that have improved gene therapy in the eye, showing that treatment of vision loss has a bright future.

  8. Advances in chest drain management in thoracic disease

    PubMed Central

    George, Robert S.

    2016-01-01

    An adequate chest drainage system aims to drain fluid and air and restore the negative pleural pressure facilitating lung expansion. In thoracic surgery the post-operative use of the conventional underwater seal chest drainage system fulfills these requirements, however they allow great variability amongst practices. In addition they do not offer accurate data and they are often inconvenient to both patients and hospital staff. This article aims to simplify the myths surrounding the management of chest drains following chest surgery, review current experience and explore the advantages of modern digital chest drain systems and address their disease-specific use. PMID:26941971

  9. Recent Advances of Vaccine Adjuvants for Infectious Diseases

    PubMed Central

    Nguyen, Minh Trang

    2015-01-01

    Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases. PMID:25922593

  10. Advances in kinase inhibition: treating rheumatic diseases and beyond

    PubMed Central

    Gadina, Massimo

    2014-01-01

    Purpose of review Kinases inhibitors are now used for the treatment of autoimmune diseases. Here are reviewed the most recent findings related to their mechanism of action and some of the newest molecules and targets which are being investigated for autoimmune and inflammatory disorders. Recent findings Similarly to p38 inhibitors, Syk inhibitors have not fulfilled the expectations of researchers and clinicians and will likely not be used therapeutically in autoimmunity. BTK inhibitors remain in the preclinical phase. Studies on the mechanism of action of successful Jak inhibitors have revealed that besides T and B cells, bone cells such as osteoclasts and innate immunity cells such as dendritic cells are positively affected. More specific, novel Jak inhibitors are now in clinical trials and newer Jak inhibitors are being developed. Other kinases are emerging from basic studies as potentially druggable and will surely be investigated. Summary First generation pan-Jak inhibitors can be useful for a wide variety of pathologies. They act on innate immune cells and can promote tolerance. More specific inhibitors will soon be available and these may be used in a disease-specific manner. PMID:24419749

  11. Therapeutic advances in the treatment of Peyronie's disease.

    PubMed

    Yafi, F A; Pinsky, M R; Sangkum, P; Hellstrom, W J G

    2015-07-01

    Peyronie's disease (PD) is an under-diagnosed condition with prevalence in the male population as high as 9%. It is a localized connective tissue disorder of the penis characterized by scarring of the tunica albuginea. Its pathophysiology, however, remains incompletely elucidated. For the management of the acute phase of PD, there are currently numerous available oral drugs, but the scientific evidence for their use is weak. In terms of intralesional injections, collagenase clostridium histolyticum is currently the only Food and Drug Administration-approved drug for the management of patients with PD and a palpable plaque with dorsal or dorsolateral curvature >30°. Other available intralesional injectable drugs include verapamil and interferon-alpha-2B, however, their use is considered off-label. Iontophoresis, shockwave therapy, and radiation therapy have also been described with unconvincing results, and as such, their use is currently not recommended. Traction therapy, as part of a multimodal approach, is an underused additional tool for the prevention of PD-associated loss of penile length, but its efficacy is dependent on patient compliance. Surgical therapy remains the gold standard for patients in the chronic phase of the disease. In patients with adequate erectile function, tunical plication and/or incision/partial excision and grafting can be offered, depending on degree of curvature and/or presence of destabilizing deformity. In patients with erectile dysfunction non-responsive to oral therapy, insertion of an inflatable penile prosthesis with or without straightening procedures should be offered.

  12. The Advancing Clinical Impact of Molecular Imaging in Cardiovascular Disease

    PubMed Central

    Osborn, Eric A; Jaffer, Farouc A

    2013-01-01

    Molecular imaging seeks to unravel critical molecular and cellular events in living subjects by providing complementary biological information to current structural clinical imaging modalities. In recent years, molecular imaging efforts have marched forward into the clinical cardiovascular arena, and are now actively illuminating new biology in a broad range of conditions, including atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm, cardiomyopathy, and valvular disease. Development of novel molecular imaging reporters is occurring for many clinical cardiovascular imaging modalities (PET, SPECT, MRI), as well in translational platforms such as intravascular fluorescence imaging. The ability to image, track, and quantify molecular biomarkers in organs not routinely amenable to biopsy (e.g. the heart and vasculature) open new clinical opportunities to tailor therapeutics based on a cardiovascular disease molecular profile. In addition, molecular imaging is playing an increasing role in atherosclerosis drug development in Phase II clinical trials. Here we present state-of-the-art clinical cardiovascular molecular imaging strategies, and explore promising translational approaches positioned for clinical testing in the near term. PMID:24332285

  13. Advances in alcoholic liver disease: An update on alcoholic hepatitis

    PubMed Central

    Liang, Randy; Liu, Andy; Perumpail, Ryan B; Wong, Robert J; Ahmed, Aijaz

    2015-01-01

    Alcoholic hepatitis is a pro-inflammatory chronic liver disease that is associated with high short-term morbidity and mortality (25%-35% in one month) in the setting of chronic alcohol use. Histopathology is notable for micro- and macrovesicular steatosis, acute inflammation with neutrophil infiltration, hepatocellular necrosis, perivenular and perisinusoidal fibrosis, and Mallory hyaline bodies found in ballooned hepatocytes. Other findings include the characteristic eosinophilic fibrillar material (Mallory’s hyaline bodies) found in ballooned hepatocytes. The presence of focal intense lobular infiltration of neutrophils is what typically distinguishes alcoholic hepatitis from other forms of hepatitis, in which the inflammatory infiltrate is primarily composed of mononuclear cells. Management consists of a multidisciplinary approach including alcohol cessation, fluid and electrolyte correction, treatment of alcohol withdrawal, and pharmacological therapy based on the severity of the disease. Pharmacological treatment for severe alcoholic hepatitis, as defined by Maddrey’s discriminant factor ≥ 32, consists of either prednisolone or pentoxifylline for a period of four weeks. The body of evidence for corticosteroids has been greater than pentoxifylline, although there are higher risks of complications. Recently head-to-head trials between corticosteroids and pentoxifylline have been performed, which again suggests that corticosteroids should strongly be considered over pentoxifylline. PMID:26576078

  14. Advancing the Minimal Residual Disease Concept in Acute Myeloid Leukemia.

    PubMed

    Hokland, Peter; Ommen, Hans B; Mulé, Matthew P; Hourigan, Christopher S

    2015-07-01

    The criteria to evaluate response to treatment in acute myeloid leukemia (AML) have changed little in the past 60 years. It is now possible to use higher sensitivity tools to measure residual disease burden in AML. Such minimal or measurable residual disease (MRD) measurements provide a deeper understanding of current patient status and allow stratification for risk of subsequent clinical relapse. Despite these obvious advantages, and after over a decade of laboratory investigation and preclinical validation, MRD measurements are not currently routinely used for clinical decision-making or drug development in non-acute promyelocytic leukemia (non-APL) AML. We review here some potential constraints that may have delayed adoption, including a natural hesitancy of end users, economic impact concerns, misperceptions regarding the meaning of and need for assay sensitivity, the lack of one single MRD solution for all AML patients, and finally the need to involve patients in decision-making based on such correlates. It is our opinion that none of these issues represent insurmountable barriers and our hope is that by providing potential solutions we can help map a path forward to a future where our patients will be offered personalized treatment plans based on the amount of AML they have left remaining to treat. PMID:26111465

  15. Current evidence base of FDG-PET/CT imaging in the clinical management of malignant pleural mesothelioma: emerging significance of image segmentation and global disease assessment.

    PubMed

    Basu, Sandip; Saboury, Babak; Torigian, Drew A; Alavi, Abass

    2011-10-01

    Increasingly, integrated positron emission tomography-computed tomography (PET/CT) imaging is playing a crucial role in the assessment of patients with known or suspected malignant pleural mesothelioma (MPM). Based on the data reported in the literature, this combined modality is likely to become the instrument of choice for examining patients of MPM. The research on this subject has focused on the following five domains: (1) differentiation of MPM from other benign pleural diseases, (2) preoperative staging for the selection of appropriate candidates for surgery, (3) evaluation for therapy response and post-treatment surveillance for recurrence, (4) prognostication based upon the intensity of 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake, and (5) planning of radiotherapy. These represent the bases for critical decision making in the management of mesothelioma, and FDG-PET/CT offers potential advantages over conventional CT imaging and thus can play a pivotal role in this regard. Optimal characterization of this potentially fatal disease with a high negative predictive value for MPM, superior capability for cancer staging initially and at the later course of disease, and ability for measuring therapeutic response and the precise determination of the target volume for radiotherapy planning represent distinct advantages of this promising molecular imaging tool. In this communication, we have explored the promising role of integrated FDG-PET/CT in the overall management of this serious malignancy. From the available data, the major role of PET-CT at present appears to be in the preoperative disease staging, response to treatment assessment, and post-treatment disease surveillance of MPM. In all these three areas, PET-CT convincingly shows better results than conventional anatomical imaging alone and thereby can aid in exploring novel therapeutic approaches. Disease prognosis and radiotherapy planning are evolving areas where this modality has demonstrated significant

  16. Advances in Susceptibility Genetics of Intervertebral Degenerative Disc Disease

    PubMed Central

    Zhang, Yin'gang; Sun, Zhengming; Liu, Jiangtao; Guo, Xiong

    2008-01-01

    The traditional view that the etiology of lumbar disc herniation is primarily due to age, gender, occupation, smoking and exposure to vehicular vibration dominated much of the last century. Recent research indicates that heredity may be largely responsible for the degeneration as well as herniation of intervertebral discs. Since 1998, genetic influences have been confirmed by the identification of several genes forms associated with disc degeneration. These researches are paving the way for a better understanding of the biologic mechanisms. Now, many researchers unanimously agree that lumbar disc herniation appears to be similar to other complex diseases, whose etiology has both environmental and hereditary influence, each with a part of contribution and relative risk. Then addressing the etiological of lumbar disc herniation, it is important to integrate heredity with the environment factors. For the purpose of this review, we have limited our discussion to several susceptibility genes associated with disc degeneration. PMID:18781226

  17. Recent advances in understanding cardiac contractility in health and disease.

    PubMed

    MacLeod, Ken T

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances.

  18. Advances in Surgical Treatment of Congenital Airway Disease.

    PubMed

    Ragalie, William S; Mitchell, Michael E

    2016-01-01

    Tracheobronchomalacia (TBM) is frequently present in infants and children with congenital heart disease (CHD). Infants with CHD and TBM appear to do worse than those without TBM. The principle of operative intervention for TBM is to improve function of the airway and clinical status. When indicated, conventional surgical options include tracheostomy, aortopexy, tracheoplasty, and anterior tracheal suspension. There is no consensus on the optimal treatment of severe tracheobonchomalacia, which can be associated with a mortality rate as high as 80%. Congenital tracheal stenosis is also frequently associated with CHD (vascular rings, atrioventricular canal defects, and septal defects) and may require concomitant repair. Repair of tracheal stenosis is often associated with distal TBM. This article addresses new techniques that can be performed in corrective surgery for both TBM and congenital tracheal stenosis. PMID:27568138

  19. Recent advances in understanding cardiac contractility in health and disease.

    PubMed

    MacLeod, Ken T

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances. PMID:27508064

  20. Recent advances in understanding cardiac contractility in health and disease

    PubMed Central

    MacLeod, Ken T.

    2016-01-01

    The aim of this review is to provide the reader with a synopsis of some of the emerging ideas and experimental findings in cardiac physiology and pathophysiology that were published in 2015. To provide context for the non-specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in the heart in health and disease is provided. Thereafter, some recently published articles are introduced that indicate the current thinking on (1) the Ca regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2) the potential influences of nitrosylation by nitric oxide or S-nitrosated proteins, (3) newly observed effects of reactive oxygen species (ROS) on contraction and Ca regulation following myocardial infarction and a possible link with changes in mitochondrial Ca, and (4) the effects of some of these signaling pathways on late Na current and pro-arrhythmic afterdepolarizations as well as the effects of transverse tubule disturbances. PMID:27508064

  1. X-ray imaging in advanced studies of ophthalmic diseases

    SciTech Connect

    Antunes, Andrea; Safatle, Angelica M. V.; Barros, Paulo S. M.; Morelhao, Sergio L.

    2006-07-15

    Microscopic characterization of pathological tissues has one major intrinsic limitation, the small sampling areas with respect to the extension of the tissues. Mapping possible changes on vast tissues and correlating them with large ensembles of clinical cases is not a feasible procedure for studying most diseases, as for instance vision loss related diseases and, in particular, the cataract. Although intraocular lens implants are successful treatments, cataract still is a leading public-health issue that grows in importance as the population increases and life expectancy is extended worldwide. In this work we have exploited the radiation-tissue interaction properties of hard x-rays--very low absorption and scattering--to map distinct lesions on entire eye lenses. At the used synchrotron x-ray photon energy of 20 keV (wavelength {lambda}=0.062 nm), scattering and refraction are angular resolved effects. It allows the employed x-ray image technique to efficiently characterize two types of lesions in eye lenses under cataractogenesis: distributions of tiny scattering centers and extended areas of fiber cell compaction. The data collection procedure is relatively fast; allowing dozens of samples to be totally imaged (scattering, refraction, and mass absorption images) in a single day of synchrotron beam time. More than 60 cases of canine cataract, not correlated to specific causes, were investigated in this first application of x-rays to image entire lenses. Cortical opacity cases, or partial opacity, could be related to the presence of calcificated tissues at the cortical areas, clearly visible in the images, whose elemental contents were verified by micro x-ray fluorescence as very rich in calcium. Calcificated tissues were also observed at nuclear areas in some cases of hypermature cataract. Total opacity cases without distinguishable amount of scattering centers consist in 70% of the analyzed cases, where remarkable fissure marks owing to extended areas of fiber

  2. X-ray imaging in advanced studies of ophthalmic diseases.

    PubMed

    Antunes, Andrea; Safatle, Angélica M V; Barros, Paulo S M; Morelhão, Sérgio L

    2006-07-01

    Microscopic characterization of pathological tissues has one major intrinsic limitation, the small sampling areas with respect to the extension of the tissues. Mapping possible changes on vast tissues and correlating them with large ensembles of clinical cases is not a feasible procedure for studying most diseases, as for instance vision loss related diseases and, in particular, the cataract. Although intraocular lens implants are successful treatments, cataract still is a leading public-health issue that grows in importance as the population increases and life expectancy is extended worldwide. In this work we have exploited the radiation-tissue interaction properties of hard x-rays--very low absorption and scattering--to map distinct lesions on entire eye lenses. At the used synchrotron x-ray photon energy of 20 keV (wavelength lambda=0.062 nm), scattering and refraction are angular resolved effects. It allows the employed x-ray image technique to efficiently characterize two types of lesions in eye lenses under cataractogenesis: distributions of tiny scattering centers and extended areas of fiber cell compaction. The data collection procedure is relatively fast; allowing dozens of samples to be totally imaged (scattering, refraction, and mass absorption images) in a single day of synchrotron beam time. More than 60 cases of canine cataract, not correlated to specific causes, were investigated in this first application of x-rays to image entire lenses. Cortical opacity cases, or partial opacity, could be related to the presence of calcificated tissues at the cortical areas, clearly visible in the images, whose elemental contents were verified by micro x-ray fluorescence as very rich in calcium. Calcificated tissues were also observed at nuclear areas in some cases of hypermature cataract. Total opacity cases without distinguishable amount of scattering centers consist in 70% of the analyzed cases, where remarkable fissure marks owing to extended areas of fiber

  3. Malignant hyperthermia.

    PubMed

    Cantin, R Y; Poole, A; Ryan, J F

    1986-10-01

    The increasing use of intravenous and inhalation sedation in the dental office has the potential of increasing the incidence of malignant hyperthermia (MH) in susceptible subjects. The object of this article is to present two cases of MH and to discuss its pathophysiology, its clinical picture, and its management in the light of the current literature. Stringent screening procedures should be adopted and maintained in order to channel suspected cases to appropriate centers for expert consultation and management. It is further advocated that a program of education for patients and their families be instituted, as it is an essential prerequisite of effective prophylaxis. PMID:2946013

  4. A prospective study of an alemtuzumab containing reduced-intensity allogeneic stem cell transplant program in patients with poor-risk and advanced lymphoid malignancies.

    PubMed

    Sauter, Craig S; Chou, Joanne F; Papadopoulos, Esperanza B; Perales, Miguel-Angel; Jakubowski, Ann A; Young, James W; Scordo, Michael; Giralt, Sergio; Castro-Malaspina, Hugo

    2014-12-01

    Reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplant (allo-SCT) have used alemtuzumab to abrogate the risk of graft-versus-host disease (GVHD). Thirty-eight patients with advanced lymphoma underwent a prospective phase II study of melphalan, fludarabine and alemtuzumab containing RIC allo-SCT from 20 matched related and 18 unrelated donors with cyclosporine-A as GVHD prophylaxis. The cumulative incidence of grade II-IV acute GVHD at 3 months was 10.5% and three evaluable patients experienced chronic GVHD. Progression-free (PFS) and overall (OS) survival at 5 years was 25% (95% confidence interval [CI]: 13-40%) and 44% (95% CI: 28-59%), respectively. Previous high-dose therapy and autologous stem cell transplant (HDT-ASCT) and elevated lactate dehydrogenase (LDH) at the time of allo-SCT resulted in inferior OS. Within this cohort of patients with high-risk lymphoma, alemtuzumab containing RIC resulted in a low risk of GVHD and a high incidence of progression of disease, especially in those with poor-risk features defined by elevated LDH pre-allo-SCT and previous HDT-ASCT.

  5. Multiparameter analysis of clastogenic factors, pro-oxidant cytokines, and inflammatory markers in HIV-1-infected patients with asymptomatic disease, opportunistic infections, and malignancies.

    PubMed Central

    Fuchs, J.; Oelke, N.; Imhof, M.; Ochsendorf, F.; Schöfer, H.; Oromek, G.; Alaoui-Youssefi, A.; Emerit, I.

    1998-01-01

    HIV-1-infected patients are in chronic oxidative stress and clastogenic factors (CFs) are present in their plasma. CFs from patients with HIV are formed via superoxide anion radical and stimulate further superoxide production. The pathophysiolgic significance and the exact composition of the circulating clastogenic material in patients with HIV is unknown. Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), are increased in the plasma of patients with HIV and TNF-alpha shows clastogenic activity in vitro. The aim of this clinical study was to compare levels of CF in HIV-1-positive patients with asymptomatic disease, opportunistic infections, and malignancies with those in HIV-1-negative control groups and to correlate CF activity with CD4+ T cell numbers, the cytokines (TNF-alpha, interleukin-2 [IL-2], IL-6), and the inflammatory markers (C-reactive protein [CRP], neopterin, granulocyte elastase). CFs were significantly increased in all HIV-1-positive patients and in HIV-1-negative patients with malignant tumors. HIV-1-positive patients with Kaposi's sarcoma showed the highest CF activity in their plasma (p < 0.08). CFs appear very early in HIV infection, and they correlate negatively with CD4+ T cells, which are an indicator of disease activity. The presence of CF in the plasma of HIV-infected patients is not a general response to a viral infection because these factors are not increased in HIV-1-negative patients with viral infection (zoster). CFs are not specific for the HIV-1 infection; they also occur in HIV-1-negative patients with malignant tumors. There was a tendency towards a positive correlation (p < 0.14) between CF and TNF-alpha but there was no positive correlation of CF with IL-2, IL-6, CRP, elastase, and neopterin levels. This indicates that TNF-alpha may be among the components of CF in HIV-1-infected patients. In addition, other unidentified components may contribute to the clastogenic activity of the plasma or the composition of CF may

  6. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

    PubMed Central

    Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

    2014-01-01

    Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

  7. Reaching Those Most in Need – A Call to Action for Advanced Parkinson’s Disease

    PubMed Central

    Agarwal, Shashank; Fleisher, Jori E

    2016-01-01

    Much of the clinical and research attention for Parkinson's Disease (PD) has focused on mild to moderate stages. As the disease advances, it can become difficult for patients to attend clinical visits. These patients are often lost to follow-up, and consequently, vanish from the pool of potential research subjects who could inform our management of this understudied population. We aim to increase awareness about this population and potential interventions to improve continuity of care and foster research in advanced PD. PMID:27708720

  8. Advancing a vaccine to prevent hookworm disease and anemia.

    PubMed

    Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia M; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

    2016-06-01

    A human hookworm vaccine is under development and in clinical trials in Africa and the Americas. The vaccine contains the Na-APR-1 and Na-GST-1 antigens. It elicits neutralizing antibodies that interfere with establishment of the adult hookworm in the gut and the ability of the parasite to feed on blood. The vaccine target product profile is focused on the immunization of children to prevent hookworm infection and anemia caused by Necator americanus. It is intended for use in low- and middle-income countries where hookworm is highly endemic and responsible for at least three million disability-adjusted life years. So far, the human hookworm vaccine is being developed in the non-profit sector through the Sabin Vaccine Institute Product Development Partnership (PDP), in collaboration with the HOOKVAC consortium of European and African partners. We envision the vaccine to be incorporated into health systems as part of an elimination strategy for hookworm infection and other neglected tropical diseases, and as a means to reduce global poverty and address the Sustainable Development Goals.

  9. Advancing a vaccine to prevent hookworm disease and anemia.

    PubMed

    Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia M; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

    2016-06-01

    A human hookworm vaccine is under development and in clinical trials in Africa and the Americas. The vaccine contains the Na-APR-1 and Na-GST-1 antigens. It elicits neutralizing antibodies that interfere with establishment of the adult hookworm in the gut and the ability of the parasite to feed on blood. The vaccine target product profile is focused on the immunization of children to prevent hookworm infection and anemia caused by Necator americanus. It is intended for use in low- and middle-income countries where hookworm is highly endemic and responsible for at least three million disability-adjusted life years. So far, the human hookworm vaccine is being developed in the non-profit sector through the Sabin Vaccine Institute Product Development Partnership (PDP), in collaboration with the HOOKVAC consortium of European and African partners. We envision the vaccine to be incorporated into health systems as part of an elimination strategy for hookworm infection and other neglected tropical diseases, and as a means to reduce global poverty and address the Sustainable Development Goals. PMID:27040400

  10. Bone disease in uremic patients: advances in PTH suppression.

    PubMed

    Brancaccio, Diego; Cozzolino, Mario; Gorio, Alfredo; Di Giulio, Anna Maria; Gallieni, Maurizio

    2002-01-01

    Chronic renal failure is often complicated by altered calcium and phosphate omeostasis. Many patients develop secondary hyperparathyroidism during the course of the disease. Therefore, both prevention and treatment of secondary hyperparathyroidism are central issues in the treatment of uremic patients. Active vitamin D metabolites are important agents in uremic patients, who have a defective activity of the renal 1alpha-hydroxylase responsible for calcitriol synthesis. Howewer, treatment with calcitriol has some limitations, namely an increase in intestinal phosphate absorption, a possible calcium overload and therefore an increase in CaxP ion product. These limitations stimulated an active research on the development of vitamin D analogs with reduced effects on intestinal transport as well as on bone mobilization of calcium and phosphate. Three vitamin D analogs, which have been used in humans, are reviewed in this article: 22-oxacalcitriol (Maxacalcitol), 19-nor-1alpha,25(OH)2 vitamin D2 (Paricalcitol), and 1alpha(OH) Vitamin D2 (Doxercalciferol). In addition, a new pharmacologic approach to the treatment of secondary hyperparathyroidism has been developed: the use of agonists for the parathyroid calcium sensing receptor, or calcimimetics. AMG O73, a second generation agent, is now under clinical evaluation in phase 3 studies, and it will soon be available in clinical practice. Given the different mechanism of action, it will be possible to use it along with vitamin D analogs and non calcemic phosphate binders. A broader spectrum of therapeutic approaches will enable the nephrologist to individually tailor the treatment of secondary hyperparathyroidism. PMID:12515379

  11. Recent advances in herbal medicines treating Parkinson's disease.

    PubMed

    Li, Xu-Zhao; Zhang, Shuai-Nan; Liu, Shu-Min; Lu, Fang

    2013-01-01

    Herbal medicines have attracted considerable attention in recent years, which are used to treat Parkinson's disease (PD) in China based on traditional Chinese medicine or modern pharmacological theories. We summarized and analyzed the anti-Parkinsonian activities of herbal medicines and herbal formulations investigated in PD models and provide future references for basic and clinical investigations. All the herbal medicines and herbal formulations were tested on PD models in vitro and in vivo. The relevant compounds and herbal extracts with anti-Parkinsonian activities were included and analyzed according to their genera or pharmacological activities. A total of 38 herbal medicines and 11 herbal formulations were analyzed. The relevant compounds, herbal extracts and formulations were reported to be effective on PD models by modulating multiple key events or signaling pathways implicated in the pathogenesis of PD. The plant species of these herbal medicines belong to 24 genera and 18 families, such as Acanthopanax, Alpinia and Astragalus, etc. These herbal medicines can be an alternative and valuable source for anti-Parkinsonian drug discovery. The plant species in these genera and families may be the most promising candidates for further investigation and deserve further consideration in clinical trials. Active components in some of the herbal extracts and the compatibility law of herbal formulations remain to be further investigated.

  12. Building a multicenter telehealth network to advance chronic disease management.

    PubMed

    Khairat, Saif; Wijesinghe, Namal; Wolfson, Julian; Scott, Rob; Simkus, Ray

    2014-01-01

    The use of telehealth solutions has proved to improve clinical management of chronic diseases, expand access to healthcare services and clinicians, and reduce healthcare-related costs. The project aims at improving Heart Failure (HF) management through the utilization of a Telemedicine and Personal Health Records systems that will assist HF specialist in Colombo, Sri Lanka to monitor and consult with remote HF patients. A telehealth network will be built at an international site that connects five remote telehealth clinics to a central clinic at a major University Hospital in Sri Lanka where HF specialists are located. In this study, 200 HF patients will be recruited for nine months, 100 patients will be randomly selected for the treatment group and the other 100 will be selected for the control group. Pre, mid, and post study surveys will be conducted to assess the efficacy and satisfaction levels of patients with both care models. Moreover, clinical outcomes will be collected to evaluate the impact of the intervention on the treatment patients compared to control patients. The research aims at enhancing Heart Failure management through eliminating current health challenges and healthcare-related financial burdens.

  13. Malignant hyperthermia

    PubMed Central

    2012-01-01

    Malignant hyperthermia (MH) is an uncommon, life-threatening pharmacogenetic disorder of the skeletal muscle. It presents as a hypermetabolic response in susceptible individuals to potent volatile anesthetics with/without depolarizing muscle relaxants; in rare cases, to stress from exertion or heat stress. Susceptibility to malignant hyperthermia (MHS) is inherited as an autosomally dominant trait with variable expression and incomplete penetrance. It is known that the pathophysiology of MH is related to an uncontrolled rise of myoplasmic calcium, which activates biochemical processes resulting in hypermetabolism of the skeletal muscle. In most cases, defects in the ryanodine receptor are responsible for the functional changes of calcium regulation in MH, and more than 300 mutations have been identified in the RYR1 gene, located on chromosome 19q13.1. The classic signs of MH include increase of end-tidal carbon dioxide, tachycardia, skeletal muscle rigidity, tachycardia, hyperthermia and acidosis. Up to now, muscle contracture test is regarded as the gold standard for the diagnosis of MHS though molecular genetic test is used, on a limited basis so far to diagnose MHS. The mortality of MH is dramatically decreased from 70-80% to less than 5%, due to an introduction of dantrolene sodium for treatment of MH, early detection of MH episode using capnography, and the introduction of diagnostic testing for MHS. This review summarizes the clinically essential and important knowledge of MH, and presents new developments in the field. PMID:23198031

  14. Eight-drug/radiation therapy program (MOPP/ABDV/RT) for advanced Hodgkin's disease

    SciTech Connect

    Straus, D.J.; Myers, J.; Passe, S.

    1980-07-15

    Eighty-four evaluable patients with advanced Hodgkin's disease (Stages IIB, IIIA age > 35 or mixed cellularity or lymphocyte depletion histology, IIIB, IVA, and IVB) were treated with alternating monthly MOPP and Adriamycin, bleomycin, dacarbazine, and vinblastine (ABDV). Radiation therapy (RT), 2000 rads in two weeks, was given to areas of initial bulky disease in untreated patients. Complete remission (CR) rates were 80% for previously untreated, 65% for prior RT or minimal chemotherapy treated, and 50% for heavily pretreated patients. Among 49 previously untreated patients there were no primary treatment failures. The estimated two-year relapse rate for the CR group was 9%. The therapeutic effectiveness of this program may have been due to either or both of the following elements: (1) two non-cross-resistant drug combinations; (2) low dose adjuvant RT to initial sites of bulky disease. These early results are among the best reported for the treatment of advanced Hodgkin's disease.

  15. [Social and health impact of advanced chronic kidney disease].

    PubMed

    Górriz Teruel, J L; Otero González, A

    2008-01-01

    The prevalence of CKD in Spain is 11%, with a high rate of associated vascular risk factors and a progressive increase in the number of patients requiring kidney replacement therapy, estimated at 5-8% annually. This has made CKD one of the leading health, social and economic problems for the health care systems of all developed countries. Kidney replacement therapy, although adequate, is not optimal for solving this clinical problem. The key aspects of the problem are: The increase in the number of patients with CKD due to: Early vascular injury as a result of the inflammatory process associated with CKD. Aging of the population, although CKD may be more dependent on comorbidities than age "per se", and prevalence may therefore not have the expected increase. The epidemic of type 2 diabetes mellitus. CKD is the major vascular risk factor both in the general and hypertensive population or patients with established vascular injury. The estimated cost of care of stage 1-4 CKD per year can be 1.6-2.4 times more than kidney replacement therapy. The approach to this serious social and health problem is based on: Early detection and diagnosis of CKD by estimation of glomerular filtration rate and assessment of associated risk factors. Establishment of treatment goals for control of cardiovascular risk factors (blood pressure, dyslipidemia, diabetes mellitus,) and albuminuria to reduce the rate of progression of kidney disease. Joint approach to problem by primary care physicians and other specialists caring for patients at high cardiovascular risk. Establishment of criteria for referral to nephrology departments.

  16. Comparative study of serum zinc concentrations in benign and malignant prostate disease: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhao, Jiang; Wu, Qingjiang; Hu, Xiaoyan; Dong, Xingyou; Wang, Liang; Liu, Qian; Long, Zhou; Li, Longkun

    2016-01-01

    Many studies have investigated the relationship between serum zinc concentration and prostatic disease, but have shown inconsistent results. Hence, we performed a systematic literature review and meta-analysis to assess the correlation between serum zinc concentration and prostate disease. Systematic literature searches were conducted with PubMed, EMBASE, Science Direct/Elsevier, MEDLINE, CNKI and the Cochrane Library up to June 2015 for studies that involved the relationship between serum zinc concentration and prostate disease. Fourteen studies were identified from the databases. Our results illustrated that the serum zinc concentrations in prostate cancer patients were significantly lower than those in Benign prostatic hyperplasia (BPH) patients and normal controls (SMD (95% CI), −0.94 [−1.57, −0.32]; −1.18 [−1.90, −0.45]). However, the serum zinc concentrations in BPH patients were significantly higher than those in normal controls (SMD (95% CI) 1.77 [0.15, 3.39]). The present study showed that different levels of serum zinc concentrations are correlated with different prostatic disease. Serum zinc concentration may be used as a tool for the diagnosis and screening of prostate disease. But, further studies with well-designed larger sample studies are needed in this field to further clarify the correlation between serum zinc concentration and prostate disease. PMID:27170414

  17. Comparative study of serum zinc concentrations in benign and malignant prostate disease: A Systematic Review and Meta-Analysis.

    PubMed

    Zhao, Jiang; Wu, Qingjiang; Hu, Xiaoyan; Dong, Xingyou; Wang, Liang; Liu, Qian; Long, Zhou; Li, Longkun

    2016-05-12

    Many studies have investigated the relationship between serum zinc concentration and prostatic disease, but have shown inconsistent results. Hence, we performed a systematic literature review and meta-analysis to assess the correlation between serum zinc concentration and prostate disease. Systematic literature searches were conducted with PubMed, EMBASE, Science Direct/Elsevier, MEDLINE, CNKI and the Cochrane Library up to June 2015 for studies that involved the relationship between serum zinc concentration and prostate disease. Fourteen studies were identified from the databases. Our results illustrated that the serum zinc concentrations in prostate cancer patients were significantly lower than those in Benign prostatic hyperplasia (BPH) patients and normal controls (SMD (95% CI), -0.94 [-1.57, -0.32]; -1.18 [-1.90, -0.45]). However, the serum zinc concentrations in BPH patients were significantly higher than those in normal controls (SMD (95% CI) 1.77 [0.15, 3.39]). The present study showed that different levels of serum zinc concentrations are correlated with different prostatic disease. Serum zinc concentration may be used as a tool for the diagnosis and screening of prostate disease. But, further studies with well-designed larger sample studies are needed in this field to further clarify the correlation between serum zinc concentration and prostate disease.

  18. Subretinal Fluid Drainage and Vitrectomy Are Helpful in Diagnosing and Treating Eyes with Advanced Coats' Disease.

    PubMed

    Imaizumi, Ayako; Kusaka, Shunji; Takaesu, Sugie; Sawaguchi, Shoichi; Shimomura, Yoshikazu

    2016-01-01

    Severe forms of Coats' disease are often associated with total retinal detachment, and a differential diagnosis from retinoblastoma is critically important. In such eyes, laser- and/or cryoablation is often ineffective or sometimes impossible to perform. We report a case of advanced Coats' disease in which a rapid pathological examination of subretinal fluid was effective for the diagnosis, and external subretinal drainage combined with vitrectomy was effective in preserving the eye. PMID:27462247

  19. Subretinal Fluid Drainage and Vitrectomy Are Helpful in Diagnosing and Treating Eyes with Advanced Coats' Disease

    PubMed Central

    Imaizumi, Ayako; Kusaka, Shunji; Takaesu, Sugie; Sawaguchi, Shoichi; Shimomura, Yoshikazu

    2016-01-01

    Severe forms of Coats' disease are often associated with total retinal detachment, and a differential diagnosis from retinoblastoma is critically important. In such eyes, laser- and/or cryoablation is often ineffective or sometimes impossible to perform. We report a case of advanced Coats' disease in which a rapid pathological examination of subretinal fluid was effective for the diagnosis, and external subretinal drainage combined with vitrectomy was effective in preserving the eye. PMID:27462247

  20. Genomic and metabolomic advances in the identification of disease and adverse event biomarkers.

    PubMed

    Mendrick, Donna L; Schnackenberg, Laura

    2009-10-01

    Incomplete knowledge of tissue pathogenesis is hampering the identification of biomarkers for the appropriate therapeutic targets to prevent or inhibit disease processes, and the prediction and diagnosis of injury due to disease and adverse events of drug therapy. The revolution in genomics and metabolomics, combined with advanced bioinformatics and computational methods for mining such large, complex data sets, are beginning to provide critical insights into tissue injury. Such results will move us closer to the promise of personalized medicine.

  1. A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies

    PubMed Central

    Mateo, Joaquin; Olmos, David; Dumez, Herlinde; Poondru, Srinivasu; Samberg, Nancy L; Barr, Sharon; Van Tornout, Jan M; Jie, Fei; Sandhu, Shahneen; Tan, Daniel S; Moreno, Victor; LoRusso, Patricia M; Kaye, Stan B; Schöffski, Patrick

    2016-01-01

    Background: The kinase activity of mTOR involves 2 multiprotein complexes, (mTORC1-mTORC2). Targeting mTORC1 with rapalogues induces compensatory feedback loops resulting in AKT/ERK activation, which may be abrogated by mTORC2 inhibition. A first-in-human trial evaluating tolerability, pharmacokinetics and pharmacodynamics of the dual TORC1/TORC2 inhibitor OSI-027 was conducted. Methods: Dose escalation was pursued for three schedules of administration (three consecutive days per week (S1), once a week (S2) and daily dosing (S3)), until dose-limiting toxicities (DLT) were identified. Expansion cohorts with paired tumour biopsies were initiated based on tolerability and pharmacodynamics. Results: One hundred and twenty eight patients with advanced cancer were enrolled. DLT consisted predominantly of fatigue, renal function disturbances and cardiac events. OSI-027 exposure was dose proportional, with Tmax within 4 h and a half-life of ∼14 h. Expansion cohorts were initiated for S1 and S2, as MTD for S3 was overall considered suboptimal. Target modulation in peripheral blood mononuclear cells were observed from 30 mg, but in tumour biopsies 120 mg QD were needed, which was a non-tolerable dose due to renal toxicity. No RECIST responses were recorded, with stable disease >6 months in six (5%) patients. Conclusions: OSI-027 inhibits mTORC1/2 in patients with advanced tumour s in a dose-dependent manner but doses above the tolerable levels in S1 and S3 are required for a sustained biological effect in tumour biopsies. PMID:27002938

  2. Advanced malignancies treated with a combination of the VEGF inhibitor bevacizumab, anti-EGFR antibody cetuximab, and the mTOR inhibitor temsirolimus

    PubMed Central

    Liu, Xiaochun; Kambrick, Susan; Fu, Siqing; Naing, Aung; Subbiah, Vivek; Blumenschein, George R.; Glisson, Bonnie S.; Kies, Merrill S.; Tsimberidou, Apostolia M.; Wheler, Jennifer J.; Zinner, Ralph G.; Hong, David S.; Kurzrock, Razelle; Piha-Paul, Sarina A.

    2016-01-01

    BACKGROUND Bevacizumab and temsirolimus are active agents in advanced solid tumors. Temsirolimus inhibits mTOR in the PI3 kinase/AKT/mTOR pathway as well as CYP2A, which may be a resistance mechanism for cetuximab. In addition, temsirolimus attenuates upregulation of HIF-1α levels, which may be a resistance mechanism for bevacizumab. RESULTS The median age of patients was 60 years (range, 23-80 years). The median number of prior systemic therapies was 3 (range, 1-6). The maximum tolerated dose (MTD) was determined to be bevacizumab 10 mg/kg biweekly, temsirolimus 5 mg weekly and cetuximab 100/75 mg/m2 weekly. Grade 3 or 4 toxicities were seen in 52% of patients with the highest prevalence being hyperglycemia (14%) and hypophosphatemia (14%). Eighteen of the 21 patients were evaluable for response. Three patients were taken off the study before restaging for toxicities. Partial response (PR) was observed in 2/18 patients (11%) and stable disease (SD) lasting ≥ 6 months was observed in 4/18 patients (22%) (total = 6/18 (33%)). In 8 evaluable patients with squamous cell carcinoma of the head and neck (HNSCC) there were partial responses in 2/8 (25%) patients and SD ≥ 6 months in 1/8 (13%) patients (total = 3/8, (38%)). PATIENTS AND METHODS We analyzed safety and responses in 21 patients with advanced solid tumors treated with bevacizumab, cetuximab, and temsirolimus. CONCLUSION The combination of bevacizumab, cetuximab, and temsirolimus showed activity in HNSCC; however, there were numerous toxicities reported, which will require careful management for future clinical development. PMID:26933802

  3. Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

    SciTech Connect

    Partl, Richard; Richtig, Erika; Avian, Alexander; Berghold, Andrea; Kapp, Karin S.

    2013-03-01

    Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.

  4. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery.

    PubMed

    Yhee, Ji Young; Im, Jintaek; Nho, Richard Seonghun

    2016-01-01

    Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed. PMID:27657144

  5. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery

    PubMed Central

    Yhee, Ji Young; Im, Jintaek; Nho, Richard Seonghun

    2016-01-01

    Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed. PMID:27657144

  6. Identifying human disease genes: advances in molecular genetics and computational approaches.

    PubMed

    Bakhtiar, S M; Ali, A; Baig, S M; Barh, D; Miyoshi, A; Azevedo, V

    2014-07-04

    The human genome project is one of the significant achievements that have provided detailed insight into our genetic legacy. During the last two decades, biomedical investigations have gathered a considerable body of evidence by detecting more than 2000 disease genes. Despite the imperative advances in the genetic understanding of various diseases, the pathogenesis of many others remains obscure. With recent advances, the laborious methodologies used to identify DNA variations are replaced by direct sequencing of genomic DNA to detect genetic changes. The ability to perform such studies depends equally on the development of high-throughput and economical genotyping methods. Currently, basically for every disease whose origen is still unknown, genetic approaches are available which could be pedigree-dependent or -independent with the capacity to elucidate fundamental disease mechanisms. Computer algorithms and programs for linkage analysis have formed the foundation for many disease gene detection projects, similarly databases of clinical findings have been widely used to support diagnostic decisions in dysmorphology and general human disease. For every disease type, genome sequence variations, particularly single nucleotide polymorphisms are mapped by comparing the genetic makeup of case and control groups. Methods that predict the effects of polymorphisms on protein stability are useful for the identification of possible disease associations, whereas structural effects can be assessed using methods to predict stability changes in proteins using sequence and/or structural information.

  7. Metastatic malignant chondroblastoma.

    PubMed

    Rodgers, W B; Mankin, H J

    1996-12-01

    A case of malignant chondroblastoma with metastases is reported. The patient initially presented with a lytic lesion in his left pubic ramus. He was treated with curettage, but the lesion recurred 3 years later. After repeated curettage, radiation therapy, and the late development of multiple bone and soft-tissue metastases, he succumbed to his disease 13 years after diagnosis. The surgical pathology from each of his several procedures was reviewed. Although no definite malignant transformation was apparent, a metastatic deposit curetted 3 months prior to death showed some increase in mitotic activity. Flow cytometry of specimens from the patient's first local recurrence and a late distant metastasis was performed and revealed the interval development of a minor aneuploid peak between the two samples. This fatal chondroblastoma is the only one in our series of 80 patients treated over the past 25 years. PMID:9001683

  8. Advances in the diagnosis and management of inflammatory bowel disease: challenges and uncertainties.

    PubMed

    Mosli, Mahmoud; Al Beshir, Mohammad; Al-Judaibi, Bandar; Al-Ameel, Turki; Saleem, Abdulaziz; Bessissow, Talat; Ghosh, Subrata; Almadi, Majid

    2014-01-01

    Over the past two decades, several advances have been made in the management of patients with inflammatory bowel disease (IBD) from both evaluative and therapeutic perspectives. This review discusses the medical advancements that have recently been made as the standard of care for managing patients with ulcerative colitis (UC) and Crohn's Disease (CD) and to identify the challenges associated with implementing their use in clinical practice. A comprehensive literature search of the major databases (PubMed and Embase) was conducted for all recent scientific papers (1990-2013) giving the recent updates on the management of IBD and the data were extracted. The reported advancements in managing IBD range from diagnostic and evaluative tools, such as genetic tests, biochemical surrogate markers of activity, endoscopic techniques, and radiological modalities, to therapeutic advances, which encompass medical, endoscopic, and surgical interventions. There are limited studies addressing the cost-effectiveness and the impact that these advances have had on medical practice. The majority of the advances developed for managing IBD, while considered instrumental by some IBD experts in improving patient care, have questionable applications due to constraints of cost, lack of availability, and most importantly, insufficient evidence that supports their role in improving important long-term health-related outcomes. PMID:24705146

  9. Advances in the Diagnosis and Management of Inflammatory Bowel Disease: Challenges and Uncertainties

    PubMed Central

    Mosli, Mahmoud; Al Beshir, Mohammad; Al-Judaibi, Bandar; Al-Ameel, Turki; Saleem, Abdulaziz; Bessissow, Talat; Ghosh, Subrata; Almadi, Majid

    2014-01-01

    Over the past two decades, several advances have been made in the management of patients with inflammatory bowel disease (IBD) from both evaluative and therapeutic perspectives. This review discusses the medical advancements that have recently been made as the standard of care for managing patients with ulcerative colitis (UC) and Crohn's Disease (CD) and to identify the challenges associated with implementing their use in clinical practice. A comprehensive literature search of the major databases (PubMed and Embase) was conducted for all recent scientific papers (1990–2013) giving the recent updates on the management of IBD and the data were extracted. The reported advancements in managing IBD range from diagnostic and evaluative tools, such as genetic tests, biochemical surrogate markers of activity, endoscopic techniques, and radiological modalities, to therapeutic advances, which encompass medical, endoscopic, and surgical interventions. There are limited studies addressing the cost-effectiveness and the impact that these advances have had on medical practice. The majority of the advances developed for managing IBD, while considered instrumental by some IBD experts in improving patient care, have questionable applications due to constraints of cost, lack of availability, and most importantly, insufficient evidence that supports their role in improving important long-term health-related outcomes. PMID:24705146

  10. The Care Needs of Community-Dwelling Seniors Suffering from Advanced Chronic Obstructive Pulmonary Disease

    ERIC Educational Resources Information Center

    Wilson, Donna M.; Ross, Carolyn; Goodridge, Donna; Davis, Penny; Landreville, Alison; Roebuck, Kim

    2008-01-01

    Aim: This study was undertaken to determine the care needs of Canadian seniors living at home with advanced chronic obstructive pulmonary disease (COPD). Background: COPD is a leading cause of morbidity and mortality worldwide. Although hospitalizations for illness exacerbations and end-stage care may be common, most persons with COPD live out…

  11. Big Fleas Have Little Fleas: How discoveries of invertebrate diseases are advancing modern science.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Review of: “Big Fleas Have Little Fleas: How discoveries of invertebrate diseases are advancing modern science”. Elizabeth W. Davdison. 2006. The University of Arizona Press, Tucson, AZ. 208 pp. Dr. Davidson links many of the accomplishments in invertebrate pathology to subsequent successes in the l...

  12. Disease evaluations and agronomic traits of advanced peanut breeding lines in 2014

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A total of 23 commercially available peanut cultivars and high-oleic advanced breeding lines were evaluated in small field plots in 2014 for agronomic traits (crop value, yield, seed grade, and characteristics) and resistance to soilborne diseases. Among the 16 runner entries evaluated, Tamrun OL11...

  13. Malignant mesothelioma

    PubMed Central

    Ahmed, Ishtiaq; Ahmed Tipu, Salman; Ishtiaq, Sundas

    2013-01-01

    Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor of the pleura and peritoneum with limited knowledge of its natural history. The incidence has increased in the past two decades but still it is a rare tumor. Etiology of all forms of mesothelioma is strongly associated with industrial pollutants, of which asbestos is the principal carcinogen. Mesothelioma is an insidious neoplasm arising from mesothelial surfaces i.e., pleura (65%-70%), peritoneum (30%), tunica vaginalis testis, and pericardium (1%-2%). The diagnosis of peritoneal and Pleural mesothelioma is often delayed, due to a long latent period between onset and symptoms and the common and nonspecific clinical presentation. The definite diagnosis can only be established by diagnostic laparoscopy or open surgery along with biopsy to obtain histological examination and immunocytochemical analysis. Different treatment options are available but Surgery can achieve a complete or incomplete resection and Radical resection is the preferred treatment. Chemotherapy has an important role in palliative treatment. Photodynamic therapy is also an option under trial. Patients who successfully underwent surgical resection had a considerably longer median survival as well as a significantly higher 5-year survival. Source of Data/Study Selection: The data were collected from case reports, cross-sectional studies, Open-label studies and phase –II trials between 1973-2012. Data Extraction: Web sites and other online resources of American college of surgeons, Medline, NCBI and Medscape resource centers were used to extract data. Conclusion: Malignant Mesothelioma (MM) is a rare but rapidly fatal and aggressive tumor with limited knowledge of its natural history. The diagnosis of peritoneal and Pleural mesothelioma is often delayed, so level of index of suspicion must be kept high. PMID:24550969

  14. Future care planning: a first step to palliative care for all patients with advanced heart disease.

    PubMed

    Denvir, M A; Murray, S A; Boyd, K J

    2015-07-01

    Palliative care is recommended for patients with end-stage heart failure with several recent, randomised trials showing improvements in symptoms and quality of life and more studies underway. Future care planning provides a framework for discussing a range of palliative care problems with patients and their families. This approach can be introduced at any time during the patient's journey of care and ideally well in advance of end-of-life care. Future care planning is applicable to a wide range of patients with advanced heart disease and could be delivered systematically by cardiology teams at the time of an unplanned hospital admission, akin to cardiac rehabilitation for myocardial infarction. Integrating cardiology care and palliative care can benefit many patients with advanced heart disease at increased risk of death or hospitalisation. Larger, randomised trials are needed to assess the impact on patient outcomes and experiences.

  15. Human epidemiology: a review of fiber type and characteristics in the development of malignant and nonmalignant disease.

    PubMed

    Merchant, J A

    1990-08-01

    Consideration of the human epidemiology of diseases arising from exposure to naturally occurring and man-made mineral fibers encompasses the several forms of asbestos (chrysotile, crocidolite, amosite, anthophyllite, tremolite-actinolite), other naturally occurring silicates (talc, sepiolite, erionite, attapulgite, vermiculite, and wollastonite), and man-made mineral fibers (glass continuous filament, glass/rock/slag insulation wools, ceramic and other refractory fibers, and glass microfibers). The diseases arising from exposures to some of these fibers include pleural thickening (plaques, diffuse pleural thickening, and calcification), pulmonary fibrosis, lung cancers, mesothelioma of the pleura and peritoneum, and other cancers). Risk factors important in assessing these diseases include assessment of latency, duration of exposure, cumulative exposure, fiber origin and characteristics (length and diameter), other possible confounding occupational or environmental exposures, and smoking. Methodological issues commonly presenting problems in evaluation of these data include assessment of the adequacy of environmental exposures, particularly in regard to fiber identification, distribution, and concentration over the duration of exposure, and the adequacy of study design to detect health effects (disease frequency, latency, and cohort size). Research priorities include further assessment and standardization of pleural thickening relative to fiber exposure, uniform mesothelioma surveillance, further epidemiological assessment of certain silicate and man-made mineral fiber cohorts with emphasis given to assessment of tremolite and small diameter glass and ceramic fibers. Further assessment of possible health risks of the general public should await improved definition of relevant fiber exposure in ambient air.

  16. CD34+ Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation for Non-Malignant Disease

    ClinicalTrials.gov

    2016-03-10

    Bone Marrow Failure Syndrome; Severe Aplastic Anemia; Severe Congenital Neutropenia; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Schwachman Diamond Syndrome; Primary Immunodeficiency Syndromes; Acquired Immunodeficiency Syndromes; Histiocytic Syndrome; Familial Hemophagocytic Lymphocytosis; Lymphohistiocytosis; Macrophage Activation Syndrome; Langerhans Cell Histiocytosis (LCH); Hemoglobinopathies; Sickle Cell Disease; Sickle Cell-beta-thalassemia

  17. Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation

    PubMed Central

    Liu, Shin-Yun; Shun, Chia-Tung; Hung, Kuan-Yu; Juan, Hsueh-Fen; Hsu, Chia-Lang; Huang, Min-Chuan; Lai, I-Rue

    2016-01-01

    Glycosylation affects malignancy in cancer. Here, we report that N- acetylgalactosaminyltransferase 2 (GALNT2), an enzyme that mediates the initial step of mucin type-O glycosylation, suppresses malignant phenotypes in gastric adenocarcinoma (GCA) by modifying MET (Hepatocyte growth factor receptor) activity. GALNT2 mRNA and protein were downregulated in GCAs, and this reduction was associated with more advanced disease stage and shorter recurrence-free survival. Suppressing GALNT2 expression in GCA cells increased cell growth, migration, and invasion in vitro, and tumor metastasis in vivo. GALNT2 knockdown enhanced phosphorylation of MET and decreased expression of the Tn antigen on MET. Inhibiting MET activity with PHA665752 decreased the malignant phenotypes caused by GALNT2 knockdown in GCA cells. Our results indicate that GALNT2 suppresses the malignant potential of GCA cells and provide novel insights into the significance of O-glycosylation in MET activity and GCA progression. PMID:26848976

  18. A Prospective Study of an Alemtuzumab Containing Reduced-intensity Allogeneic Stem Cell Transplantation Program in Patients with Poor-Risk and Advanced Lymphoid Malignancies

    PubMed Central

    Sauter, Craig S.; Chou, Joanne F.; Papadopoulos, Esperanza B.; Perales, Miguel-Angel; Jakubowski, Ann A.; Young, James W.; Scordo, Michael; Giralt, Sergio; Castro-Malaspina, Hugo

    2015-01-01

    Reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT) have used alemtuzumab to abrogate the risk of graft-versus-host disease (GVHD). Thirty-eight advanced lymphoma patients underwent a prospective phase II study of melphalan, fludarabine and alemtuzumab containing RIC allo-SCT from 20 matched related and 18 unrelated donors with cyclosporin-A as GVHD prophylaxis. The cumulative incidence of grade II-IV acute GVHD at 3 months was 10.5% and three evaluable patients experienced chronic GVHD. Progression-free (PFS) and overall (OS) survival at 5 years is 25% (95% CI: 13-40) and 44% (95% CI: 28-59%) respectively. Previous high-dose therapy and autologous stem cell transplantation (HDT-ASCT) and elevated LDH at the time of allo-SCT resulted in inferior OS. Within this cohort of high-risk lymphoma patients, alemtuzumab containing RIC resulted in a low risk of GVHD and a high incidence of POD, especially in those with poor-risk features defined by elevated LDH pre-allo-SCT and previous HDT-ASCT. PMID:24528216

  19. Phase I Trial of 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (17-DMAG), a Heat Shock Protein Inhibitor, Administered Twice Weekly in Patients with Advanced Malignancies

    PubMed Central

    Kummar, Shivaani; Gutierrez, Martin E.; Gardner, Erin R.; Chen, Xiaohong; Figg, William D.; Zajac-Kaye, Maria; Chen, Min; Steinberg, Seth M.; Muir, Christine A.; Yancey, Mary Ann; Horneffer, Yvonne R.; Juwara, Lamin; Melillo, Giovanni; Ivy, S. Percy; Merino, Maria; Neckers, Len; Steeg, Patricia S.; Conley, Barbara A.; Giaccone, Giuseppe; Doroshow, James H.; Murgo, Anthony J.

    2009-01-01

    Purpose Phase I dose-escalation study to determine the toxicity and maximum tolerated dose (MTD) of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, administered on a twice weekly schedule in patients with advanced cancer. Experimental Design 17-DMAG was administered as a 1- to 2-h infusion twice weekly in 4-week cycles. An accelerated titration design was followed until toxicity was observed, at which point standard dose escalation proceeded. MTD was defined as the dose at which no more than one of six patients experienced a dose-limiting toxicity (DLT). Pharmacokinetics were assessed, and Hsp70 mRNA, whose gene product is a chaperone previously shown to be upregulated following inhibition of Hsp90, was measured in peripheral blood mononuclear cells (PBMCs). Results A total of 31 patients received 92 courses of treatment. The MTD was 21 mg/m2/d; 20 patients were enrolled at this dose level. Nine patients had stable disease for a median of 4 (range 2-22) months. Both Cmax and AUC increased proportionally with dose. The most common toxicities were grade 1 or 2 fatigue, anorexia, nausea, blurred vision, and musculoskeletal pain. DLTs were peripheral neuropathy and renal dysfunction. Expression of Hsp70 mRNA in PBMCs was highly variable. Conclusion Twice-weekly i.v. infusion of 17-DMAG is well tolerated, and combination phase I studies are warranted. PMID:19945858

  20. A rare and sinister variant of a common ailment: Fungal malignant otitis externa

    PubMed Central

    Lilic, N; Mowjood, MT; Wong, MHW

    2012-01-01

    A recent case report in this journal highlighted the pathophysiology and management of bacterial malignant otitis externa (MOE) (1). We describe the case of an elderly gentleman who had a delayed diagnosis of fungal MOE with advanced diseased at time of diagnosis. This case highlights the changing microbiology of this serious disease and the difficulty in diagnosis given the rarity of this form of otitis externa relative to its uncomplicated form. PMID:24960790

  1. Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease

    PubMed Central

    Grove, J; Daly, A; Bassendine, M; Gilvarry, E; Day, C

    2000-01-01

    BACKGROUND—The factors determining why less than 10% of heavy drinkers develop advanced alcoholic liver disease (ALD) remain elusive, although genetic factors may be important. Interleukin 10 (IL-10) is an important cytokine with anti-inflammatory, anti-immune, and antifibrotic functions. Several polymorphisms have been identified in the IL-10 promoter and recent evidence suggests that some of these may have functional effects on IL-10 secretion.
AIMS—To test the hypothesis that IL-10 promoter region polymorphisms are associated with susceptibility to ALD.
METHODS—The allele frequencies for the two single base pair substitutions at positions −627 (C→A) and −1117 (A→G) in the IL-10 promoter were determined in 287 heavy drinkers with biopsy proved advanced ALD, 107 heavy drinkers with no evidence of liver disease or steatosis only on biopsy, and 227 local healthy volunteers.
RESULTS—At position −627, 50% of patients with advanced ALD had a least one A allele compared with 33% of controls (p<0.0001) and 34% of drinkers with no or mild disease (p=0.017). At position −1117, the slight excess of the A allele in drinkers with advanced disease was because of linkage disequilibrium between the A alleles at the two sites.
CONCLUSIONS—Among heavy drinkers, possession of the A allele at position −627 in the IL-10 promoter is associated with an increased risk of advanced liver disease. This is consistent with recent functional data that the −627*A allele is associated with low IL-10 expression which will favour inflammatory, immune mediated, and profibrotic mechanisms of alcohol related liver injury.


Keywords: ethyl alcohol; cirrhosis; interleukin 10; genetic polymorphism PMID:10716685

  2. Immunoglobulin G4+ B‐cell receptor clones distinguish immunoglobulin G 4‐related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies

    PubMed Central

    Doorenspleet, Marieke E.; Hubers, Lowiek M.; Culver, Emma L.; Maillette de Buy Wenniger, Lucas J.; Klarenbeek, Paul L.; Chapman, Roger W.; Baas, Frank; van de Graaf, Stan F.; Verheij, Joanne; van Gulik, Thomas M.; Barnes, Eleanor; de Vries, Niek

    2016-01-01

    Immunoglobulin G4 (IgG4)‐related disease (IgG4‐RD) of the biliary tree and pancreas is difficult to distinguish from sclerosing cholangitis and biliary/pancreatic malignancies (CA). An accurate noninvasive test for diagnosis and monitoring of disease activity is lacking. We demonstrate that dominant IgG4+ B‐cell receptor (BCR) clones determined by next‐generation sequencing accurately distinguish patients with IgG4‐associated cholangitis/autoimmune pancreatitis (n = 34) from those with primary sclerosing cholangitis (n = 17) and CA (n = 17). A novel, more affordable, and widely applicable quantitative polymerase chain reaction (qPCR) protocol analyzing the IgG4/IgG RNA ratio in blood also achieves excellent diagnostic accuracy (n = 125). Moreover, this qPCR test performed better than serum IgG4 levels in sensitivity (94% vs. 86%) and specificity (99% vs. 73%) and correlates with treatment response (n = 20). Conclusions: IgG4+ BCR clones and IgG4/IgG RNA ratio markedly improve delineation, early diagnosis, and monitoring of IgG4‐RD of the biliary tree and pancreas. (Hepatology 2016;64:501‐507) PMID:27015613

  3. Advances in understanding and treating liver diseases during pregnancy: A review

    PubMed Central

    Kamimura, Kenya; Abe, Hiroyuki; Kawai, Hirokazu; Kamimura, Hiroteru; Kobayashi, Yuji; Nomoto, Minoru; Aoyagi, Yutaka; Terai, Shuji

    2015-01-01

    Liver disease in pregnancy is rare but pregnancy-related liver diseases may cause threat to fetal and maternal survival. It includes pre-eclampsia; eclampsia; haemolysis, elevated liver enzymes, and low platelets syndrome; acute fatty liver of pregnancy; hyperemesis gravidarum; and intrahepatic cholestasis of pregnancy. Recent basic researches have shown the various etiologies involved in this disease entity. With these advances, rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival. The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention. Therefore, correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis. Therefore, here we review and summarized recent advances in understanding the etiologies, clinical courses and management of liver disease in pregnancy. This information will contribute to physicians for diagnosis of disease and optimum management of patients. PMID:25954092

  4. Recent advances in molecular medicine techniques for the diagnosis, prevention, and control of infectious diseases.

    PubMed

    França, R F O; da Silva, C C; De Paula, S O

    2013-06-01

    In recent years we have observed great advances in our ability to combat infectious diseases. Through the development of novel genetic methodologies, including a better understanding of pathogen biology, pathogenic mechanisms, advances in vaccine development, designing new therapeutic drugs, and optimization of diagnostic tools, significant infectious diseases are now better controlled. Here, we briefly describe recent reports in the literature concentrating on infectious disease control. The focus of this review is to describe the molecular methods widely used in the diagnosis, prevention, and control of infectious diseases with regard to the innovation of molecular techniques. Since the list of pathogenic microorganisms is extensive, we emphasize some of the major human infectious diseases (AIDS, tuberculosis, malaria, rotavirus, herpes virus, viral hepatitis, and dengue fever). As a consequence of these developments, infectious diseases will be more accurately and effectively treated; safe and effective vaccines are being developed and rapid detection of infectious agents now permits countermeasures to avoid potential outbreaks and epidemics. But, despite considerable progress, infectious diseases remain a strong challenge to human survival. PMID:23339016

  5. Recent advances in molecular medicine techniques for the diagnosis, prevention, and control of infectious diseases.

    PubMed

    França, R F O; da Silva, C C; De Paula, S O

    2013-06-01

    In recent years we have observed great advances in our ability to combat infectious diseases. Through the development of novel genetic methodologies, including a better understanding of pathogen biology, pathogenic mechanisms, advances in vaccine development, designing new therapeutic drugs, and optimization of diagnostic tools, significant infectious diseases are now better controlled. Here, we briefly describe recent reports in the literature concentrating on infectious disease control. The focus of this review is to describe the molecular methods widely used in the diagnosis, prevention, and control of infectious diseases with regard to the innovation of molecular techniques. Since the list of pathogenic microorganisms is extensive, we emphasize some of the major human infectious diseases (AIDS, tuberculosis, malaria, rotavirus, herpes virus, viral hepatitis, and dengue fever). As a consequence of these developments, infectious diseases will be more accurately and effectively treated; safe and effective vaccines are being developed and rapid detection of infectious agents now permits countermeasures to avoid potential outbreaks and epidemics. But, despite considerable progress, infectious diseases remain a strong challenge to human survival.

  6. How have advances in our understanding of the molecular genetics of paediatric leukaemia led to improved targeted therapies for these diseases?

    PubMed

    Szychot, Elwira; Brodkiewicz, Andrzej; Peregud-Pogorzelski, Jarosław

    2014-01-01

    The term "leukaemia" refers to a large and heterogenous group of diseases, with treatment response and outcome dependent on the specific type of malignancy. New molecular methods allow us to specifically evaluate the type of disorder, and provide treatment of necessary intensity. The aim of this review is to provide insight into the progress in leukaemia treatment that had been possible due to advances in molecular genetics over the last few decades. Those new sophisticated diagnostic methods have allowed us not only to predict patients' prognosis but also to provide a specific therapy depending on the molecular and genetic characteristics of patients. Our review is based on 25 articles regarding novel diagnostic and therapeutic methods as well as prognostic factors, released between 1992 and 2011. Those articles focus mostly on molecular and cytogenetic testing allowing revolutionary methods of patient classification and individual therapy for this highly heterogeneous group of disorders. Implementation of molecular genetic testing to evaluate the type of leukaemia allowed paediatric oncologists and haematologists to adjust the intensity of treatment, improve outcome, minimize toxicity of therapies and considerably lower the risk of side effects. In the last few decades there has been a great improvement in survival among children suffering from haematopoietic malignancies. Progress made in molecular genetics allowed the creation of new treatment protocols that are designed to maintain a high cure rate for children with leukaemia while reducing toxicity.

  7. Human epidemiology: A review of fiber type and characteristics in the development of malignant and nonmalignant disease

    SciTech Connect

    Merchant, J.A. )

    1990-08-01

    Consideration of the human epidemiology of diseases arising from exposure to naturally occurring and man-made mineral fibers encompasses the several forms of asbestos, other naturally occurring silicates, and man-made mineral fibers. The diseases arising from exposures to some of these fibers include pleural thickening, pulmonary fibrosis, lung cancers, mesothelioma of the pleura and peritoneum, and other cancers. Risk factors important in assessing these diseases include assessment of latency, duration of exposure, cumulative exposure, fiber origin and characteristics, other possible confounding occupational or environmental exposures, and smoking. Methodological issues commonly presenting problems in evaluation of these data include assessment of the adequacy of environmental exposures, particularly in regard to fiber identification, distribution, and concentration over the duration of exposure, and the adequacy of study design to detect health effects. Research priorities include further assessment and standardization of pleural thickening relative to fiber exposure, uniform mesothelioma surveillance, further epidemiological assessment of certain silicate and man-made mineral fiber cohorts with emphasis given to assessment of tremolite and small diameter glass and ceramic fibers. Further assessment of possible health risks of the general public should await improved definition of relevant fiber exposure in ambient air.

  8. The significance of HER-2/neu/c-erbB-2 gene amplification in benign and malignant breast disease.

    PubMed

    Supanaranond, K; Sukarayodhin, S; Tanyakaset, M; Balachandra, K; Jullaksorn, D; Rienkijkarn, M; Hoisanka, N; Tantivanich, S

    1997-09-01

    This study was carried out to investigate the amplification of HER-2/neu oncogene in 66 patients with primary breast cancer and 90 samples from benign breast disease (BBD). The amplification of HER-2/neu oncogene in the DNA of paraffin-embedded specimens was determined by differential PCR. Nineteen out of 66 (28.8%) breast cancer patients showed amplification of the gene. No gene amplification was found in benign breast disease. There was no significant correlation of HER-2/neu amplification with, age, menopausal status, the number of positive nodes, tumor size, estrogen receptor, however, amplification of HER-2/neu gene was strongly correlated with nodal status (p = 0.0049). In node positive patients, the incidence of HER-2/neu amplification was high (43%). These findings indicate that the amplification of HER-2/neu gene may be of pathogenetic significance in breast cancer and may have a poor prognosis in node positive breast cancer patients while no gene amplification in benign breast disease suggests that HER-2/neu amplification is a late molecular alteration event in the pathogenesis of breast cancer.

  9. A review of advances in the study of diseases of fish: 1954-1964

    USGS Publications Warehouse

    Post, G.

    1965-01-01

    STUDY OF DISEASE IN ANIMALS, INCLUDING MAN, has progressed rapidly in the past decade. Looking back, we find amazing success in the study of man's diseases and possibly only a little less success in studies of diseases of domesticated homeothermic animals. We who are interested in the poikilothermic animals may feel at times that we have not advanced so rapidly in our field. The reason for this may be closely associated with economics. The market for drugs and therapeutic agents is greater for domestic livestock than for cultured fishes. A larger income is derived from rearing domestic livestock. Therefore, more public funds are available for study of diseases of man and domestic livestock, while such funds are limited for the study of diseases of fish. The Federal and State fish-cultural systems, as well as colleges and universities, have been most active in research on fish disease and probably will continue to be so.

  10. Aspirin-Exacerbated Diseases: Advances in Asthma with Nasal Polyposis, Urticaria, Angioedema, and Anaphylaxis.

    PubMed

    Stevens, Whitney; Buchheit, Kathleen; Cahill, Katherine N

    2015-12-01

    Aspirin-exacerbated diseases are important examples of drug hypersensitivities and include aspirin-exacerbated respiratory disease (AERD), aspirin- or non-steroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema, and aspirin- or NSAID-induced anaphylaxis. While each disease subtype may be distinguished by unique clinical features, the underlying mechanisms that contribute to these phenotypes are not fully understood. However, the inhibition of the cyclooxygenase-1 enzyme is thought to play a significant role. Additionally, eosinophils, mast cells, and their products, prostaglandins and leukotrienes, have been identified in the pathogenesis of AERD. Current diagnostic and treatment strategies for aspirin-exacerbated diseases remain limited, and continued research focusing on each of the unique hypersensitivity reactions to aspirin is essential. This will not only advance the understanding of these disease processes, but also lead to the subsequent development of novel therapeutics that patients who suffer from aspirin-induced reactions desperately need.

  11. Unrelated donor hematopoietic stem cell transplantation for the treatment of non-malignant genetic diseases: An alemtuzumab based regimen is associated with cure of clinical disease; earlier clearance of alemtuzumab may be associated with graft rejection.

    PubMed

    Abdel-Azim, Hisham; Mahadeo, Kris Michael; Zhao, Quan; Khazal, Sajad; Kohn, Donald B; Crooks, Gay M; Shah, Ami J; Kapoor, Neena

    2015-11-01

    Hematopoietic stem cell transplantation (HSCT) with matched unrelated donors (MUD), offers potentially curative therapy for patients with non-malignant genetic diseases. In this pilot study conducted from 2006 to 2014, we report the outcomes of 15 patients with non-malignant genetic diseases who received a myeloablative regimen with a reduced cyclophosphamide dose, adjunctive serotherapy and MUD HSCT [intravenous alemtuzumab (52 mg/m(2) ), busulfan (16 mg/kg), fludarabine (140mg/m(2) ), and cyclophosphamide (105 mg/kg)]. Graft-versus-host-disease (GVHD) prophylaxis consisted of tacrolimus/cyclosporine and methylprednisolone. Median (range) time to neutrophil engraftment (>500 cells/µL) and platelet engraftment (>20,000/mm(3) ) were 15 (12-28) and 25 (17-30) days, respectively. At a median follow-up of 2 (0.2-5.4) years, the overall survival (OS) was 93.3% (95% CI: 0.61-0.99) and disease-free survival (DFS) was 73.3% (95% CI: 0.44-0.89). Among this small sample, earlier alemtuzumab clearance was significantly associated with graft rejection (P = 0.047), earlier PHA response (P = 0.009) and a trend toward earlier recovery of recent thymic emigrants (RTE) (P = 0.06). This regimen was associated with durable donor engraftment and relatively low rates of regimen related toxicity (RRT); future alemtuzumab pharmacokinetic studies may improve outcomes, by allowing targeted alemtuzumab clearance to reduce graft rejection and promote more rapid immune reconstitution.

  12. [Malignant hyperthermia].

    PubMed

    Metterlein, T; Schuster, F; Graf, B M; Anetseder, M

    2014-12-01

    Malignant hyperthermia (MH) is a rare hereditary, mostly subclinical myopathy. Trigger substances, such as volatile anesthetic agents and the depolarizing muscle relaxant succinylcholine can induce a potentially fatal metabolic increase in predisposed patients caused by a dysregulation of the myoplasmic calcium (Ca) concentration. Mutations in the dihydropyridine ryanodine receptor complex in combination with the trigger substances are responsible for an uncontrolled release of Ca from the sarcoplasmic reticulum. This leads to activation of the contractile apparatus and a massive increase in cellular energy production. Exhaustion of the cellular energy reserves ultimately results in local muscle cell destruction and subsequent cardiovascular failure. The clinical picture of MH episodes is very variable. Early symptoms are hypoxia, hypercapnia and cardiac arrhythmia whereas the body temperature rise, after which MH is named, often occurs later. Decisive for the course of MH episodes is a timely targeted therapy. Following introduction of the hydantoin derivative dantrolene, the previously high mortality of fulminant MH episodes could be reduced to well under 10 %. An MH predisposition can be detected using the invasive in vitro contracture test (IVCT) or mutation analysis. Few elaborate diagnostic procedures are in the developmental stage. PMID:25384957

  13. Malignant hyperthermia

    MedlinePlus

    ... a disease that causes a fast rise in body temperature and severe muscle contractions when someone with the ... is passed down through families. Hyperthermia means high body temperature. This condition is not the same as hyperthermia ...

  14. Nonalcoholic Lipid Accumulation and Hepatocyte Malignant Transformation

    PubMed Central

    Gu, Juanjuan; Yao, Min; Yao, Dengbing; Wang, Li; Yang, Xuli; Yao, Dengfu

    2016-01-01

    Abstract Worldwide incidence of hepatocellular carcinoma (HCC) is steadily increasing, highlighting its status as a public health concern, particularly due to its significant association with other comorbidities, such as diabetes. However, nonalcoholic fatty liver disease (NAFLD) has emerged as a primary risk factor, with its own prevalence increasing in recent years, and it has gradually caught up with the historical primary etiological factors of infection with hepatitis B virus and hepatitis C virus, exposure to aflatoxin, or alcohol liver disease. The deeply worrisome aspects of all of these high risk factors, however, are their remarkable presence within populations. Systemic and genetic mechanisms involved in the malignant transformation of liver cells, as well as useful biomarkers of early stage HCC are being investigated. However, the exact mechanisms underlying the interrelation of NAFLD and HCC remain largely unknown. In this review, some of the recent advances in our understanding of liver lipid accumulation are summarized and discussed to provide insights into the relationship between NAFLD and hepatocyte malignant transformation. PMID:27350942

  15. Advances in Cell and Gene-based Therapies for Cystic Fibrosis Lung Disease

    PubMed Central

    Oakland, Mayumi; Sinn, Patrick L; McCray Jr, Paul B

    2012-01-01

    Cystic fibrosis (CF) is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Yet, physical and host immune barriers in the lung present challenges for successful gene transfer to the respiratory tract. Advances in gene transfer approaches, tissue engineering, and novel animal models are generating excitement within the CF research field. This review discusses current challenges and advancements in viral and nonviral vectors, cell-based therapies, and CF animal models. PMID:22371844

  16. A retrospective study on malignant neoplasms of bladder, lung and liver in blackfoot disease endemic area in Taiwan.

    PubMed

    Chen, C J; Chuang, Y C; You, S L; Lin, T M; Wu, H Y

    1986-03-01

    A total of 69 bladder cancer, 76 lung cancer and 59 liver cancer deceased cases and 368 alive community controls group-matched on age and sex were studied to evaluate the association between high-arsenic artesian well water and cancers in the endemic area of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous arsenic exposure. According to a standardized structured questionnaire, information on risk factors was obtained through proxy interview of the cases and personal interview of the controls. A positive dose-response relationship was observed between the exposure to artesian well water and cancers of bladder, lung and liver. The age-sex-adjusted odds ratios of developing bladder, lung and liver cancers for those who had used artesian well water for 40 or more years were 3.90, 3.39, and 2.67, respectively, as compared with those who never used artesian well water. Multiple binary logistic regression analyses showed that the dose-response relationships and odds ratios remained much the same while other risk factors were further adjusted.

  17. Advanced therapeutic endoscopist and inflammatory bowel disease: Dawn of a new role

    PubMed Central

    Modha, Kunjam; Navaneethan, Udayakumar

    2014-01-01

    Endoscopy plays a key role in the diagnosis and treatment of patients with inflammatory bowel disease (IBD). Colonoscopy has been traditionally used in the diagnosis of IBD and helps in determination of an important end point in patient management, “mucosal healing”. However, the involvement of an advanced endoscopist has expanded with innovations in therapeutic and newer imaging techniques. Endoscopists are increasingly being involved in the management of anastomotic and small bowel strictures in these patients. The advent of balloon enteroscopy has helped us access areas not deemed possible in the past for dilations. An advanced endoscopist also plays an integral part in managing ileal pouch-anal anastomosis complications including management of pouch strictures and sinuses. The use of rectal endoscopic ultrasound has been expanded for imaging of perianal fistulae in patients with Crohn’s disease and appears much more sensitive than magnetic resonance imaging and exam under anesthesia. Advanced endoscopists also play an integral part in detection of dysplasia by employing advanced imaging techniques. In fact the paradigm for neoplasia surveillance in IBD is rapidly evolving with advancements in endoscopic imaging technology with pancolonic chromoendoscopy becoming the main imaging modality for neoplasia surveillance in IBD patients in most institutions. Advanced endoscopists are also called upon to diagnose primary sclerosing cholangitis (PSC) and also offer options for endoscopic management of strictures through endoscopic retrograde cholangiopancreatography (ERCP). In addition, PSC patients are at increased risk of developing cholangiocarcinoma with a 20% lifetime risk. Brush cytology obtained during ERCP and use of fluorescence in situ hybridization which assesses the presence of chromosomal aneuploidy (abnormality in chromosome number) are established initial diagnostic techniques in the investigation of patients with biliary strictures. Thus advanced

  18. A Phase I Study of a Combination of Yttrium-90 labeled Anti-CEA Antibody and Gemcitabine in Patients with CEA Producing Advanced Malignancies

    PubMed Central

    Shibata, Stephen; Raubitschek, Andrew; Leong, Lucille; Koczywas, Marianna; Williams, Lawrence; Zhan, Jiping; Wong, Jeffrey Y.C.

    2011-01-01

    Purpose To determine the maximum tolerated dose of combined therapy using an yttrium-90 labeled anti-CEA antibody with gemcitabine in patients with advanced CEA producing solid tumors. Experimental Design The chimeric human/murine cT84.66 is an anti-CEA intact IgG1, with high affinity and specificity to CEA. This was given at a fixed yttrium-90 labeled dose of 16.6 mCi/m2 to subjects who had and an elevated CEA in serum or in tumor by immunohistochemistry. Also required was a tumor that imaged with an 111In labeled cT84.66 antibody. Patients were treated with escalating doses of gemcitabine given intravenously over 30 minutes on day 1 and 3 after the infusion of the yttrium-90 labeled antibody. Patients were treated in cohorts of 3. The maximum tolerated dose was determined as the highest level at which no more than 1 of 6 patients experienced a dose limiting toxicity. Results A total of 36 patients were enrolled, and all but one had prior systemic therapy. The maximum tolerated dose of gemcitabine in this combination was 150mg/m2. Dose limiting toxicities at a gemcitabine dose of 165mg/m2 included a grade 3 rash and grade 4 neutropenia. One partial response was seen in a patient with colorectal cancer, and 4 patients had a > 50% decrease in baseline CEA levels associated with stable disease. Human antichimeric antibody responses were the primary reason for stopping treatment in 12 patients. Conclusions feasibility of combining gemcitabine with an yttrium-90 labeled anti-CEA antibody is demonstrated with preliminary evidence of clinical response. PMID:19351765

  19. Leuloplakia - Review of A Potentially Malignant Disorder

    PubMed Central

    Abidullah, Mohammed; Gaddikeri, Kavitha; Raghoji, Swetha; Ravishankar T, Shilpa

    2014-01-01

    Leukoplakias are oral white lesions that have not been diagnosed as any other specific disease. They are grouped under premalignant lesions, now redesignated as potentially malignant disorders. Their significance lies in the fact that they have propensity for malignant transformation at a higher rate when compared to other oral lesions. This article reviews aetiology, epidemiology, clinical characteristics, histopathologic features, malignant potential and treatment of oral leukoplakia. PMID:25302287

  20. Asbestos-related malignancy.

    PubMed

    Talcott, J A; Antman, K H

    1988-01-01

    Asbestos-associated malignancies have received significant attention in the lay and medical literature because of the increasing frequency of two asbestos-associated tumors, lung carcinoma and mesothelioma; the wide distribution of asbestos; its status as a prototype environmental carcinogen; and the many recent legal compensation proceedings, for which medical testimony has been required. The understanding of asbestos-associated carcinogenesis has increased through study of animal models, human epidemiology, and, recently, the application of modern molecular biological techniques. However, the detailed mechanisms of carcinogenesis remain unknown. A wide variety of malignancies have been associated with asbestos, although the strongest evidence for a causal association is confined to lung cancer and mesothelioma. Epidemiological studies have provided evidence that both the type of asbestos fiber and the industry in which the exposure occurs may affect the rates of asbestos-associated cancers. It has been shown that asbestos exerts a carcinogenic effect independent of exposure to cigarette smoking that, for lung cancers, is synergistically enhanced by smoking. Other questions remain controversial, such as whether pulmonary fibrosis necessarily precedes asbestos-associated lung cancer and whether some threshold level of exposure to asbestos (including low-dose exposures that may occur in asbestos-associated public buildings) may be safe. Mesothelioma, the most closely asbestos-associated malignancy, has a dismal natural history and has been highly resistant to therapy. However, investigational multi-modality therapy may offer benefit to some patients. A description of the processes through which compensation claims for asbestos-associated malignancies are evaluated illustrates for physicians the legal system's approach to possible injury from toxic substances. The differences between scientific and legal reasoning about the causes of diseases with long latency

  1. Congenital heart disease and rheumatic heart disease in Africa: recent advances and current priorities

    PubMed Central

    Zühlke, Liesl; Mirabel, Mariana; Marijon, Eloi

    2013-01-01

    Africa has one of the highest prevalence of heart diseases in children and young adults, including congenital heart disease (CHD) and rheumatic heart disease (RHD). We present here an extensive review of recent data from the African continent highlighting key studies and information regarding progress in CHD and RHD since 2005. Main findings include evidence that the CHD burden is underestimated mainly due to the poor outcome of African children with CHD. The interest in primary prevention for RHD has been recently re-emphasised, and new data are available regarding echocardiographic screening for subclinical RHD and initiation of secondary prevention. There is an urgent need for comprehensive service frameworks to improve access and level of care and services for patients, educational programmes to reinforce the importance of prevention and early diagnosis and a relevant research agenda focusing on the African context. PMID:23680886

  2. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria.

    PubMed

    Dubois, Bruno; Feldman, Howard H; Jacova, Claudia; Hampel, Harald; Molinuevo, José Luis; Blennow, Kaj; DeKosky, Steven T; Gauthier, Serge; Selkoe, Dennis; Bateman, Randall; Cappa, Stefano; Crutch, Sebastian; Engelborghs, Sebastiaan; Frisoni, Giovanni B; Fox, Nick C; Galasko, Douglas; Habert, Marie-Odile; Jicha, Gregory A; Nordberg, Agneta; Pasquier, Florence; Rabinovici, Gil; Robert, Philippe; Rowe, Christopher; Salloway, Stephen; Sarazin, Marie; Epelbaum, Stéphane; de Souza, Leonardo C; Vellas, Bruno; Visser, Pieter J; Schneider, Lon; Stern, Yaakov; Scheltens, Philip; Cummings, Jeffrey L

    2014-06-01

    In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD. PMID:24849862

  3. Post-Thaw Viable CD45+ Cells and Clonogenic Efficiency are Associated with Better Engraftment and Outcomes after Single Cord Blood Transplantation in Adult Patients with Malignant Diseases.

    PubMed

    Castillo, Nerea; García-Cadenas, Irene; Barba, Pere; Martino, Rodrigo; Azqueta, Carmen; Ferrà, Christelle; Canals, Carme; Sierra, Jorge; Valcárcel, David; Querol, Sergio

    2015-12-01

    The quantity of cells is widely accepted as the main factor influencing the outcome after umbilical cord blood transplantation (UCBT) however, the quality of the cord blood units (CBUs) has been less studied. In order to determine the impact of qualitative variables in UCBT outcomes, we conducted a multicenter retrospective study in adult patients with hematological malignancies who underwent single UCBT after a common myeloablative conditioning regimen. One hundred and ten patients from 3 institutions [median age, 35 years (range 18-55)] were included. Quantitative (TNC and total CD34+cells) and qualitative variables [viable CD45+ (vCD45+), vCD34+ and clonogenic efficiency [(CLONE), quotient of post-thaw colony-forming units (CFU)] and pre-freeze CD34+ cells predicted engraftment in univariate analysis however, only 2 qualitative variables remained significant in the multivariate analysis. Infusion of more than 2 × 10(7) post-thaw vCD45+ cells per kilogram was significantly associated with faster neutrophil (P = .01), platelet engraftment (P = .01), higher disease-free (P = .01) and overall survival (0.02). In addition, CLONE ≥ 20% predicted a faster neutrophil (P = .005), platelet engraftment (P = .01) and contributed to decrease the non-relapse mortality (P = .02). Our study suggests that the vCD45+ cells dose and CLONE are powerful surrogate markers of graft quality and can potentially help on CBUs selection if tested with representative reference samples.

  4. Respiratory Cancer and Non-Malignant Respiratory Disease-Related Mortality among Older Construction Workers-Findings from the Health and Retirement Study

    PubMed Central

    Wang, Xuanwen; Dong, Xiuwen Sue; Welch, Laura; Largay, Julie

    2016-01-01

    Objective This study explored the risk of respiratory cancer and non-malignant respiratory disease (NMRD)-related mortality among older construction workers. Methods Analyzed data from the 1992–2010 RAND Health and Retirement Study (HRS) and the HRS National Death Index – Cause of Death file. About 25,183 workers aged 50 years and older were examined, including 5,447 decedents and 19,736 survivors, of which 1,460 reported their longest job was in construction. Multinomial logistic regression assessed the differences in mortality between workers’ longest occupations, controlling for confounders. Results After adjusting for smoking and demographics, construction workers were almost twice as likely to die from respiratory cancer (OR = 1.65; CI: 1.10–2.47) or NMRD (OR = 1.73; CI: 1.16–2.58) compared to white-collar workers. Conclusions This study adds to the growing evidence that respiratory cancer and NMRD are frequently associated with construction exposure. PMID:27500180

  5. Advances in the prevention of oral disease; the role of the International Association for Dental Research

    PubMed Central

    2015-01-01

    Abstract Background Since its foundation in 1920, prevention of oral disease has been a priority for the International Association for Dental Research (IADR) and the commitment of the organisation to the subject area is clearly expressed in its mission to improve oral health worldwide. The IADR has a current global membership of almost 11,000 people who share an interest in oral and craniofacial research. Contribution of IADR This paper provides an overview of the contribution of IADR to supporting research and associated activities in disease prevention, in disseminating knowledge and in advocating for better oral health for all citizens of the world. It looks back over time and summarises current supports. Two more recent initiatives in disease prevention are described in more detail, the Global Oral Health Inequalities Research Agenda (GOHIRA) and the proceedings at the 2013 World Conference on Preventive Dentistry (WCPD, 2013), a joint initiative between IADR and WHO. Through organisational structure, meetings, publications, scientific groups and networks and external relations, IADR has been at the forefront of advancing research for the prevention of oral diseases. Conclusions IADR is committed to ensuring research advances get disseminated and implemented and at the same time encourages and advocates for basic, clinical and translational research across disciplines so that we may uncover the major breakthrough in prevention of oral disease. PMID:26391001

  6. Dynamic tension EMG to characterize the effects of DBS treatment of advanced Parkinson's disease.

    PubMed

    Ruonala, V; Pekkonen, E; Rissanen, S; Airaksinen, O; Miroshnichenko, G; Kankaanpää, M; Karjalainen, P

    2014-01-01

    Deep brain stimulation (DBS) is an effective treatment method for motor symptoms of advanced Parkinson's disease. DBS-electrode is implanted to subthalamic nucleus to give precisely allocated electrical stimuli to brain. The optimal stimulus type has to be adjusted individually. Disease severity, main symptoms and biological factors play a role in correctly setting up the device. Currently there are no objective methods to assess the efficacy of DBS, hence the adjustment is based solely on clinical assessment. In optimal case an objectively measurable feature would point the right settings of DBS. Surface electromyographic and kinematic measurements have been used in Parkinson's disease research. As Parkinson's disease symptoms are known to change the EMG signal properties, these methods could be helpful aid in the clinical adjustment of DBS. In this study, 13 patients with advanced Parkinson's disease who received DBS treatment were measured. The patients were measured with seven different settings of the DBS in clinical range including changes in stimulation amplitude, frequency and pulse width. The EMG analysis was based on parameters that characterize EMG signal morphology. Correlation dimension and recurrence rate made the most significant difference in relation to optimal settings. In conclusion, EMG analysis is able to detect differences between the DBS setups, and can help in finding the correct parameters. PMID:25570683

  7. Prospects in cancer immunotherapy: treating advanced stage disease or preventing tumor recurrence?

    PubMed

    Manjili, Masoud H; Payne, Kyle K

    2015-06-01

    Human vaccines against infectious agents are often effective in a prophylactic setting. However, they are usually not effective when used post-exposure. Rabies vaccine is one of the exceptions, which can be used post-exposure, but is effective only when used in combination with other treatments. Similar results have been obtained with cancer vaccines and immunotherapies. Cancer immunotherapies generally prolong patients' survival when they are used during advanced stage disease. The potential of immunotherapy to cure cancer could be revealed when it is applied in a prophylactic setting. This article provides a brief overview of cancer immunotherapeutics and suggests that immunotherapy can cure cancer if used at the right time against the right target; we suggest that targeting cancer during dormancy in order to prevent tumor recurrence as advanced stage disease is potentially curative.

  8. Cryptococcus neoformans infection in malignancy.

    PubMed

    Schmalzle, Sarah A; Buchwald, Ulrike K; Gilliam, Bruce L; Riedel, David J

    2016-09-01

    Cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in HIV-infected persons. Malignancy and its treatment may also confer a higher risk of infection with Cryptococcus neoformans, but this association has not been as well described. A case of cryptococcosis in a cancer patient is presented, and all cases of coincident C. neoformans infection and malignancy in adults published in the literature in English between 1970 and 2014 are reviewed. Data from these cases were aggregated in order to describe the demographics, type of malignancy, site of infection, clinical manifestations, treatment and outcomes of cryptococcosis in patients with cancer. Haematologic malignancies accounted for 82% of cases, with lymphomas over-represented compared to US population data (66% vs. 53% respectively). Cryptococcosis was reported rarely in patients with solid tumours. Haematologic malignancy patients were more likely to have central nervous system (P < 0.001) or disseminated disease (P < 0.001), receive Amphotericin B as part of initial therapy (P = 0.023), and had higher reported mortality rates than those with solid tumours (P = 0.222). Providers should have heightened awareness of the possibility of cryptococcosis in patients with haematologic malignancy presenting with infection. PMID:26932366

  9. Extra-intestinal malignancies in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (III).

    PubMed

    Magro, Fernando; Peyrin-Biroulet, Laurent; Sokol, Harry; Aldeger, Xavier; Costa, Antonia; Higgins, Peter D; Joyce, Joel C; Katsanos, Konstantinos H; Lopez, Anthony; de Xaxars, Teresa Mas; Toader, Elena; Beaugerie, Laurent

    2014-01-01

    The incidence of lymphoproliferative disorders (LD) is increasing in developed countries. Patients with inflammatory bowel disease (IBD) exposed to thiopurines are at additional risk of three specific forms of LD: Epstein-Barr-Virus-related post-transplant like LD, hepato-splenic T-cell lymphoma and post-mononucleosis lymphoproliferation. The risk of the two latter forms of LD can be reduced when considering specific immunosuppressive strategies in young males. It is still unclear whether the risk of uterine cervix abnormalities is increased in IBD women, irrespective of the use of immunosuppressants. Given the excess risk demonstrated in various other contexts of immunosuppression, it is currently recommended that all women with IBD, particularly those receiving immunosuppressants, strictly adhere to a screening program of cervical surveillance and undergo vaccination against HPV, when appropriate. Patients with IBD receiving immunosuppressants are at increased risk of skin cancers. The risk of non-melanoma skin cancer is notably increased in patients receiving thiopurines. Recent data suggest that the risk of melanoma is mildly increased in patients exposed to anti-TNF therapy. All IBD patients should adhere to a program of sun protection and dermatological surveillance, whose details should take into account the other non-IBD-related risk factors.

  10. Extra-intestinal malignancies in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (III).

    PubMed

    Magro, Fernando; Peyrin-Biroulet, Laurent; Sokol, Harry; Aldeger, Xavier; Costa, Antonia; Higgins, Peter D; Joyce, Joel C; Katsanos, Konstantinos H; Lopez, Anthony; de Xaxars, Teresa Mas; Toader, Elena; Beaugerie, Laurent

    2014-01-01

    The incidence of lymphoproliferative disorders (LD) is increasing in developed countries. Patients with inflammatory bowel disease (IBD) exposed to thiopurines are at additional risk of three specific forms of LD: Epstein-Barr-Virus-related post-transplant like LD, hepato-splenic T-cell lymphoma and post-mononucleosis lymphoproliferation. The risk of the two latter forms of LD can be reduced when considering specific immunosuppressive strategies in young males. It is still unclear whether the risk of uterine cervix abnormalities is increased in IBD women, irrespective of the use of immunosuppressants. Given the excess risk demonstrated in various other contexts of immunosuppression, it is currently recommended that all women with IBD, particularly those receiving immunosuppressants, strictly adhere to a screening program of cervical surveillance and undergo vaccination against HPV, when appropriate. Patients with IBD receiving immunosuppressants are at increased risk of skin cancers. The risk of non-melanoma skin cancer is notably increased in patients receiving thiopurines. Recent data suggest that the risk of melanoma is mildly increased in patients exposed to anti-TNF therapy. All IBD patients should adhere to a program of sun protection and dermatological surveillance, whose details should take into account the other non-IBD-related risk factors. PMID:23721759

  11. Malignant T cells express lymphotoxin α and drive endothelial activation in cutaneous T cell lymphoma

    PubMed Central

    Lauenborg, Britt; Christensen, Louise; Ralfkiaer, Ulrik; Kopp, Katharina L.; Jønson, Lars; Dabelsteen, Sally; Bonefeld, Charlotte M.; Geisler, Carsten; Gjerdrum, Lise Mette R.; Zhang, Qian; Wasik, Mariusz A.; Ralfkiaer, Elisabeth; Ødum, Niels; Woetmann, Anders

    2015-01-01

    Lymphotoxin α (LTα) plays a key role in the formation of lymphatic vasculature and secondary lymphoid structures. Cutaneous T cell lymphoma (CTCL) is the most common primary lymphoma of the skin and in advanced stages, malignant T cells spreads through the lymphatic to regional lymph nodes to internal organs and blood. Yet, little is known about the mechanism of the CTCL dissemination. Here, we show that CTCL cells express LTα in situ and that LTα expression is driven by aberrantly activated JAK3/STAT5 pathway. Importantly, via TNF receptor 2, LTα functions as an autocrine factor by stimulating expression of IL-6 in the malignant cells. LTα and IL-6, together with VEGF promote angiogenesis by inducing endothelial cell sprouting and tube formation. Thus, we propose that LTα plays a role in malignant angiogenesis and disease progression in CTCL and may serve as a therapeutic target in this disease. PMID:25915535

  12. Managing uncertainty in advanced liver disease: a qualitative, multiperspective, serial interview study

    PubMed Central

    Kimbell, Barbara; Boyd, Kirsty; Kendall, Marilyn; Iredale, John; Murray, Scott A

    2015-01-01

    Objective To understand the experiences and support needs of people with advanced liver disease and those of their lay and professional carers to inform improvements in the supportive and palliative care of this rapidly growing but currently neglected patient group. Design Multiperspective, serial interviews. We conducted up to three qualitative in-depth interviews with each patient and lay carer over 12 months and single interviews with case-linked healthcare professionals. Data were analysed using grounded theory techniques. Participants Patients with advanced liver disease of diverse aetiologies recruited from an inpatient hepatology ward, and their lay carers and case-linked healthcare professionals nominated by the patients. Setting Primary and secondary care in South-East Scotland. Results 37 participants (15 patients, 11 lay and 11 professional carers) completed 51 individual and 13 joint patient-carer interviews. Nine patients died during the study. Uncertainty dominated experiences throughout the course of the illness, across patients’ considerable physical, psychological, social and existential needs and affected patients, lay carers and professionals. This related to the nature of the condition, the unpredictability of physical deterioration and prognosis, poor communication and information-sharing, and complexities of care. The pervasive uncertainty also shaped patients’ and lay carers’ strategies for coping and impeded care planning. While patients’ acute medical care was usually well coordinated, their ongoing care lacked structure and focus. Conclusions Living, dying and caring in advanced liver disease is dominated by pervasive, enduring and universally shared uncertainty. In the face of high levels of multidimensional patient distress, professionals must acknowledge this uncertainty in constructive ways that value its contribution to the person's coping approach. Pervasive uncertainty makes anticipatory care planning in advanced liver

  13. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    PubMed

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  14. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms

    PubMed Central

    Mooney, Michael A.; Simon, Elias D.; Little, Andrew S.

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  15. Advances in huntington disease drug discovery: novel approaches to model disease phenotypes.

    PubMed

    Bard, Jonathan; Wall, Michael D; Lazari, Ovadia; Arjomand, Jamshid; Munoz-Sanjuan, Ignacio

    2014-02-01

    Huntington disease is a monogenic, autosomal dominant, progressive neurodegenerative disorder caused by a trinucleotide CAG repeat expansion in exon 1 of the huntingtin (HTT) gene; age of onset of clinical symptoms inversely correlates with expanded CAG repeat length. HD leads to extensive degeneration of the basal ganglia, hypothalamic nuclei, and selected cortical areas, and a wide range of molecular mechanisms have been implicated in disease pathology in animal or cellular models expressing mutated HTT (mHTT) proteins, either full-length or amino-terminal fragments. However, HD cellular models that recapitulate the slow progression of the disease have not been available due to the toxicity of overexpressed exogenous mHTT or to limitations with using primary cells for long-term studies. Most investigations of the effects of mHTT relied on cytotoxicity or aggregation end points in heterologous systems or in primary embryonic neuroglial cultures derived from HD mouse models. More innovative approaches are currently under active investigation, including screening using electrophysiological endpoints, as well as the recent use of primary blood mononuclear cells and of human embryonic stem cells derived from a variety of HD research participants. Here we describe how these cellular systems are being used to investigate HD biology as well as to identify mechanisms with therapeutic potential.

  16. Wildebeest-associated malignant catarrhal fever: perspectives for integrated control of a lymphoproliferative disease of cattle in sub-Saharan Africa.

    PubMed

    Wambua, Lillian; Wambua, Peninah Nduku; Ramogo, Allan Maurice; Mijele, Domnic; Otiende, Moses Yongo

    2016-01-01

    Wildebeest-associated malignant catarrhal fever (WA-MCF), an acute lymphoproliferative disease of cattle caused by alcelaphine herpesvirus 1 (AlHV-1), remains a significant constraint to cattle production in nomadic pastoralist systems in eastern and southern Africa. The transmission of WA-MCF is dependent on the presence of the wildlife reservoir, i.e. wildebeest, belonging to the species Connochaetes taurinus and Connochaetes gnou; hence, the distribution of WA-MCF is largely restricted to Kenya, Tanzania and the Republic of South Africa, where wildebeest are present. WA-MCF is analogous to sheep-associated MCF (SA-MCF) in many aspects, with the latter having sheep as its reservoir host and a more global distribution, mainly in developed countries with intensive livestock production systems. However, unlike SA-MCF, the geographic seclusion of WA-MCF may have contributed to an apparent neglect in research efforts aimed at increased biological understanding and control of the disease. This review aims to highlight the importance of WA-MCF and the need for intensified research towards measures for its integrated control. We discuss current knowledge on transmission and geographical distribution in eastern and southern Africa and the burden of WA-MCF in affected vulnerable pastoral communities in Africa. Recent findings towards vaccine development and pertinent knowledge gaps for future research efforts on WA-MCF are also considered. Finally, integrated control of WA-MCF based on a logical three-pronged framework is proposed, contextualizing vaccine development, next-generation diagnostics, and diversity studies targeted to the viral pathogen and cattle hosts. PMID:26446889

  17. Deep Assessment: A Novel Framework for Improving the Care of People with Very Advanced Alzheimer's Disease

    PubMed Central

    Lyons, Gordon; Arthur-Kelly, Michael; Eidels, Ami; Mavratzakis, Aimee

    2015-01-01

    Best practice in understanding and caring for people with advanced Alzheimer's disease presents extraordinary challenges. Their severe and deteriorating cognitive impairments are such that carers find progressive difficulty in authentically ascertaining and responding to interests, preferences, and needs. Deep assessment, a novel multifaceted framework drawn from research into the experiences of others with severe cognitive impairments, has potential to empower carers and other support professionals to develop an enhanced understanding of people with advanced Alzheimer's disease and so deliver better calibrated care in attempts to maximize quality of life. Deep assessment uses a combination of techniques, namely, Behaviour State Observation, Triangulated Proxy Reporting, and Startle Reflex Modulation Measurement, to deliver a comprehensive and deep assessment of the inner states (awareness, preferences, likes, and dislikes) of people who cannot reliably self-report. This paper explains deep assessment and its current applications. It then suggests how it can be applied to people with advanced Alzheimer's disease to develop others' understanding of their inner states and to help improve their quality of life. An illustrative hypothetical vignette is used to amplify this framework. We discuss the potential utility and efficacy of this technique for this population and we also propose other human conditions that may benefit from research using a deep assessment approach. PMID:26688817

  18. Deep Assessment: A Novel Framework for Improving the Care of People with Very Advanced Alzheimer's Disease.

    PubMed

    Lyons, Gordon; Arthur-Kelly, Michael; Eidels, Ami; Mavratzakis, Aimee

    2015-01-01

    Best practice in understanding and caring for people with advanced Alzheimer's disease presents extraordinary challenges. Their severe and deteriorating cognitive impairments are such that carers find progressive difficulty in authentically ascertaining and responding to interests, preferences, and needs. Deep assessment, a novel multifaceted framework drawn from research into the experiences of others with severe cognitive impairments, has potential to empower carers and other support professionals to develop an enhanced understanding of people with advanced Alzheimer's disease and so deliver better calibrated care in attempts to maximize quality of life. Deep assessment uses a combination of techniques, namely, Behaviour State Observation, Triangulated Proxy Reporting, and Startle Reflex Modulation Measurement, to deliver a comprehensive and deep assessment of the inner states (awareness, preferences, likes, and dislikes) of people who cannot reliably self-report. This paper explains deep assessment and its current applications. It then suggests how it can be applied to people with advanced Alzheimer's disease to develop others' understanding of their inner states and to help improve their quality of life. An illustrative hypothetical vignette is used to amplify this framework. We discuss the potential utility and efficacy of this technique for this population and we also propose other human conditions that may benefit from research using a deep assessment approach. PMID:26688817

  19. ‘Reality and desire’ in the care of advanced chronic kidney disease

    PubMed Central

    Marrón, Belén; Craver, Lourdes; Remón, César; Prieto, Mario; Gutiérrez, Josep Mª; Ortiz, Alberto

    2010-01-01

    There is a long distance between the actual worldwide reality in advanced chronic kidney disease care and the desire of how these patients should be managed to decrease cardiovascular and general morbidity and mortality. Implementation of adequate infrastructures may improve clinical outcomes and increase the use of home renal replacement therapies (RRT). Current pitfalls should be addressed to optimise care: inadequate medical training for nephrological referral and RRT selection, late referral to nephrologists, inadequate patient education for choice of RRT modality, lack of multidisciplinary advanced kidney disease clinics and lack of programmed RRT initiation. These deficiencies generate unintended consequences, such as inequality of care and limitations in patient education and selection-choice for RRT technique with limited use of peritoneal dialysis. Multidisciplinary advanced kidney disease clinics may have a direct impact on patient survival, morbidity and quality of life. There is a common need to reduce health care costs and scenarios increasing PD incidence show better efficiency. The following proposals may help to improve the current situation: defining the scope of the problem, disseminating guidelines with specific targets and quality indicators, optimising medical speciality training, providing adequate patient education, specially through the use of general decision making tools that will allow patients to choose the best possible RRT in accordance with their values, preferences and medical advice, increasing planned dialysis starts and involving all stakeholders in the process. PMID:25984045

  20. 'Reality and desire' in the care of advanced chronic kidney disease.

    PubMed

    Marrón, Belén; Craver, Lourdes; Remón, César; Prieto, Mario; Gutiérrez, Josep M; Ortiz, Alberto

    2010-10-01

    There is a long distance between the actual worldwide reality in advanced chronic kidney disease care and the desire of how these patients should be managed to decrease cardiovascular and general morbidity and mortality. Implementation of adequate infrastructures may improve clinical outcomes and increase the use of home renal replacement therapies (RRT). Current pitfalls should be addressed to optimise care: inadequate medical training for nephrological referral and RRT selection, late referral to nephrologists, inadequate patient education for choice of RRT modality, lack of multidisciplinary advanced kidney disease clinics and lack of programmed RRT initiation. These deficiencies generate unintended consequences, such as inequality of care and limitations in patient education and selection-choice for RRT technique with limited use of peritoneal dialysis. Multidisciplinary advanced kidney disease clinics may have a direct impact on patient survival, morbidity and quality of life. There is a common need to reduce health care costs and scenarios increasing PD incidence show better efficiency. The following proposals may help to improve the current situation: defining the scope of the problem, disseminating guidelines with specific targets and quality indicators, optimising medical speciality training, providing adequate patient education, specially through the use of general decision making tools that will allow patients to choose the best possible RRT in accordance with their values, preferences and medical advice, increasing planned dialysis starts and involving all stakeholders in the process.

  1. The Origin of Malignant Malaria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasmodium falciparum is the causative agent of malignant malaria, which is among the most severe human infectious diseases. Despite its overwhelming significance to human health, the parasite’s origins remain unclear. The favored origin hypothesis holds that P. falciparum and its closest known rel...

  2. Obesity: The Metabolic Disease, Advances on Drug Discovery and Natural Product Research.

    PubMed

    Castro, Mafalda; Preto, Marco; Vasconcelos, Vitor; Urbatzka, Ralph

    2016-01-01

    Obesity is a global health threat. OECD reported that more than half (52%) of the adult population in the European Union is overweight or obese. Obesity and obesity-related co-morbidities have deep negative effects on morbidity, mortality, professional and personal quality of life. Healthcare costs represent a negative impact of this disease, with an associated economic cost of 100 billion US$ per year in the United States. The most prescribed drugs for obesity treatment worldwide are orlistat, and phentermine/topiramate extended release, while the major prescribed drug for the same disease in the US are exenatide and dapagliflozin. The so far developed drugs, targeting weight loss, have a long history of malignant secondary effects. There is still a lack of efficient and safe drugs to treat obesity and related metabolic complications since in many cases cure cannot be reached by bariatric surgery or healthy lifestyle habits. Terrestrial and aquatic organisms are a promising source of valuable, bioactive compounds, often with interest for human health. Some of the natural compounds or organisms have been used for centuries by humans as traditional medicine foods. In this review, we give insights into the adipose tissue function and development, and the progress in traditional anti-obesity pharmacotherapy. A major focus is to highlight the state of the art of natural compounds with anti-obesity properties and their potential as candidates for drug development; an overview is given about natural compounds derived from different marine animal sources, cyanobacteria, marine phytoplankton, fungus or plants. PMID:27086785

  3. Obesity: The Metabolic Disease, Advances on Drug Discovery and Natural Product Research.

    PubMed

    Castro, Mafalda; Preto, Marco; Vasconcelos, Vitor; Urbatzka, Ralph

    2016-01-01

    Obesity is a global health threat. OECD reported that more than half (52%) of the adult population in the European Union is overweight or obese. Obesity and obesity-related co-morbidities have deep negative effects on morbidity, mortality, professional and personal quality of life. Healthcare costs represent a negative impact of this disease, with an associated economic cost of 100 billion US$ per year in the United States. The most prescribed drugs for obesity treatment worldwide are orlistat, and phentermine/topiramate extended release, while the major prescribed drug for the same disease in the US are exenatide and dapagliflozin. The so far developed drugs, targeting weight loss, have a long history of malignant secondary effects. There is still a lack of efficient and safe drugs to treat obesity and related metabolic complications since in many cases cure cannot be reached by bariatric surgery or healthy lifestyle habits. Terrestrial and aquatic organisms are a promising source of valuable, bioactive compounds, often with interest for human health. Some of the natural compounds or organisms have been used for centuries by humans as traditional medicine foods. In this review, we give insights into the adipose tissue function and development, and the progress in traditional anti-obesity pharmacotherapy. A major focus is to highlight the state of the art of natural compounds with anti-obesity properties and their potential as candidates for drug development; an overview is given about natural compounds derived from different marine animal sources, cyanobacteria, marine phytoplankton, fungus or plants.

  4. Role of laparoscopy in hepatobiliary malignancies.

    PubMed

    Arumugam, Prabhu; Balarajah, Vickna; Watt, Jennifer; Abraham, Ajit T; Bhattacharya, Satyajit; Kocher, Hemant M

    2016-04-01

    The many benefits of laparoscopy, including smaller incision, reduced length of hospital stay and more rapid return to normal function, have seen its popularity grow in recent years. With concurrent improvements in non-surgical cancer management the importance of accurate staging is becoming increasingly important. There are two main applications of laparoscopic surgery in managing hepato-pancreatico-biliary (HPB) malignancy: accurate staging of disease and resection. We aim to summarize the use of laparoscopy in these contexts. The role of staging laparoscopy has become routine in certain cancers, in particular T[2] staged, locally advanced gastric cancer, hilar cholangiocarcinoma and non-Hodgkin's lymphoma. For other cancers, in particular colorectal, laparoscopy has now become the gold standard management for resection such that there is no role for stand-alone staging laparoscopy. In HPB cancers, although staging laparoscopy may play a role, with ever improving radiology, its role remains controversial. PMID:27377496

  5. [Malignant lymphoma].

    PubMed

    Asano, Naoko; Nakamura, Shigeo

    2014-06-01

    The WHO classification, considered as a bible for lymphoma diagnosis, is a list of disease units. It is expected that it will fully classify all diseases based on indicators with objectivity of constants, even in the present state, in which it cannot be said that the source, causes, and tumorigenesis mechanisms have been identified for all neoplasms. The indicators are the histology, phenotype, genotype, and clinical picture. In the current WHO classification, these indicators are described for each diseases unit, and considered as diagnostic items. While the importance of items which serve as indicators differ depending on each illness, the pathologic centering on a morphological finding does not change for lymphoma diagnosis in accordance with this WHO classification. An indispensable factor in order to evaluate this objective of pathologic diagnosis is phenotypic and genotype assessment. A phenotype is analyzed by immunohistochemistry techniques, and a genotype is clarified by various gene chromosome tests. Diagnostic applications using these test results are developed as follows: 1. Histological diagnosis based on the immunohistochemical features of lymphoma cells, 2. Identification of oncogene products, 3. Evaluation of biological prognostic factors, 4. Analysis of the inflammatory microenvironment of tumor cells. This paper describes all items. PMID:25151780

  6. Treatment of Parkinson disease: a 64-year-old man with motor complications of advanced Parkinson disease.

    PubMed

    Tarsy, Daniel

    2012-06-01

    In early stages, Parkinson disease typically begins with asymmetric or unilateral motor symptoms due to combinations of mild bradykinesia, rigidity, and tremor. In most cases, with progression, signs of more generalized bradykinesia appear, which include facial masking, reduced voice volume, and slowing of activities of daily living. In more advanced Parkinson disease, other disabling manifestations may follow, such as impaired balance, gait freezing, falls, speech disturbance, and cognitive impairment. Levodopa is the most effective medical treatment for Parkinson disease. However, motor complications uniquely related to levodopa treatment may emerge that may be difficult to manage. These include fluctuating levodopa responses and involuntary movements and postures known as dyskinesia and dystonia. Medication adjustments are usually effective, but in some cases surgical intervention with deep brain stimulation becomes necessary to alleviate motor complications. The case of Mr L, a man with an 11-year history of Parkinson disease, illustrates these emerging motor complications and the manner in which they may be managed both medically and surgically.

  7. Endoscopic transnasal management of sinonasal malignancies – our initial experience

    PubMed Central

    Osuch-Wójcikiewicz, Ewa; Held-Ziółkowska, Marta; Kużmińska, Magdalena; Niemczyk, Kazimierz

    2014-01-01

    Introduction Malignant tumors of the paranasal sinuses are traditionally managed through external approaches. Advances in endoscopic transnasal surgery have allowed for the endoscopic treatment of some of these tumors. Aim To present the results of treatment of a series of patients with paranasal sinus malignancies treated with an endoscopic approach at a single institution. Material and methods The data on tumor type, operative technique, perioperative complications and postoperative course were analyzed. Results Eleven patients meeting the inclusion criteria were identified. The histopathology was as follows: malignant melanoma in 3 patients, squamous cell carcinoma in 2, adenocarcinoma in 2, poorly differentiated carcinoma in 1, hemangiopericytoma in 1, adenoid cystic carcinoma in 1 and fibrosarcoma in 1. There were no severe perioperative complications with the exception of 1 case of cerebrospinal fluid leak, which was successfully closed. The mean observation period was 13.5 months. One of the patients died of disease, another was lost to follow-up, and one was reoperated on due to recurrence. The remaining 8 patients are alive with no signs of recurrence. Conclusions Our initial experience seems to confirm results obtained by other authors indicating that in selected cases endoscopic surgery of sinonasal malignancies is similarly effective as external approach surgery. PMID:25097677

  8. Malignant hyperthermia and the general dentist: current recommendations.

    PubMed

    Haas, D A; Young, E R; Harper, D G

    1992-01-01

    Malignant hyperthermia is a potentially fatal disease that may be triggered by the administration of specific drugs or by stress. Although most often associated with general anesthesia, stress can be a significant stimulus and is therefore of concern to the general dentist. The decision as to how and where to treat these patients is complicated by conflicting recommendations from various sources. The aim of this article is to propose a protocol for the dentist to use in the treatment of patients with a history of malignant hyperthermia. The dentist must assess the patient for both their susceptibility to a crisis and the degree of stress of the planned procedure. For non-stressful treatment, it is reasonable to assume that the general dental practitioner can treat these patients in his office. For stressful treatment, advanced preparation is advised. PMID:1531939

  9. Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies.

    PubMed

    Kidane, Biniam; Hirpara, Dhruvin; Yasufuku, Kazuhiro

    2016-01-21

    Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve.

  10. Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies

    PubMed Central

    Kidane, Biniam; Hirpara, Dhruvin; Yasufuku, Kazuhiro

    2016-01-01

    Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve. PMID:26805818

  11. GPs’ views on managing advanced chronic kidney disease in primary care: a qualitative study

    PubMed Central

    Tonkin-Crine, Sarah; Santer, Miriam; Leydon, Geraldine M; Murtagh, Fliss EM; Farrington, Ken; Caskey, Fergus; Rayner, Hugh; Roderick, Paul

    2015-01-01

    Background Chronic kidney disease (CKD) has become a significant part of the GP’s workload since the introduction of the National Institute for Health and Care Excellence guidelines in 2008. Patients with advanced CKD (stages G4 and G5) often have comorbidities, varied disease progression, and are likely to be older. GPs may experience difficulties with management decisions for patients with advanced CKD, including when to refer to nephrology. Aim To explore GPs’ views of managing patients with advanced CKD and referral to secondary care. Design and setting Qualitative study with GPs in four areas of England: London, Bristol, Birmingham, and Stevenage. Method Semi-structured interviews with 19 GPs. Transcribed interviews were thematically analysed. Results GPs had little experience of managing patients with advanced CKD, including those on dialysis or having conservative care (treatment without dialysis or a transplant), and welcomed guidance. Some GPs referred patients based on renal function alone and some used wider criteria including age and multimorbidity. GPs reported a tension between national guidance and local advice, and some had learnt from experience that patients were discharged back to primary care. GPs with more experience of managing CKD referred patients later, or sometimes not at all, if there were no additional problems and if dialysis was seen as not in the patient’s interests. Conclusion GPs want guidance on managing older patients with advanced CKD and comorbidities, which better incorporates agreement between local and national recommendations to clarify referral criteria. GPs are not generally aware of conservative care programmes provided by renal units, however, they appear happy to contribute to such care or alternatively, lead conservative management with input from renal teams. PMID:26120137

  12. Predictive and preventive strategies to advance the treatments of cardiovascular and cerebrovascular diseases: the Ukrainian context

    PubMed Central

    2012-01-01

    Despite great efforts in treatments of cardiovascular diseases, the field requires innovative strategies because of high rates of morbidity, mortality and disability, indicating evident deficits in predictive vascular diagnosis and individualized treatment approaches. Talking about the vascular system, currently, physicians are not provided with integrated medical approaches to diagnose and treat vascular diseases. Only an individual global approach to the analysis of all segments in the vascular system of a patient allows finding the optimal way for vascular disease treatment. As for the existing methodology, there is a dominance of static methods such as X-ray contrast angiography and magnetic resonance imaging in angiomode. Taking into account the world experience, this article deals with innovative strategies, aiming at predictive diagnosis in vascular system, personalization of the biomedical treatment approaches, and targeted prevention of individual patient cohorts. Clinical examples illustrate the advances in corresponding healthcare sectors. Recommendations are provided to promote the field. PMID:23083430

  13. [Research advances on role of microRNAs in congenital heart diseases].

    PubMed

    Yan, Hua-Lin; Hua, Yi-Min

    2014-10-01

    MicroRNAs (miRNAs) are a class of small non-coding RNAs, which mainly regulate gene expression through post-transcriptional process. They are highly conserved, tissue-specific and highly specific in miRNA-binding on 3'-untranslated regions. MicroRNAs have been identified as crucial regulators in myocardial cell proliferation, differentiation and apoptosis, migration of cardiac neural crest cells, cardiac morphogenesis and cardiac patterning processes, which may provide a new insight into the research on developmental mechanism of congenital heart diseases. The research on miRNAs in congenital heart diseases includes clinical research and animal experiments. This article reviews two types of research advances, the mechanism of congenital heart diseases, and the current status and limitation of the domestic reports.

  14. Nonsurgical Management of Cervical Cancer: Locally Advanced, Recurrent, and Metastatic Disease, Survivorship, and Beyond

    PubMed Central

    Mackay, Helen J.; Wenzel, Lari; Mileshkin, Linda

    2016-01-01

    Overview Despite the declining incidence of cervical cancer as a result of the introduction of screening programs, globally it remains a leading cause of cancer-related death in women. Outcomes for patients who are diagnosed with anything but early-stage disease remain poor. Here we examine emerging strategies to improve the treatment of locally advanced disease. We discuss emerging biologic data, which are informing our investigation of new therapeutic interventions in persistent, recurrent, and metastatic cervical cancer. We recognize the importance of interventions to improve quality of life and to prevent long-term sequelae in women undergoing treatment. Finally, and perhaps most importantly, we recognize the need for global collaboration and advocacy to improve the outcome for all women at risk of and diagnosed with this disease. PMID:25993189

  15. Update on celiac disease – etiology, differential diagnosis, drug targets, and management advances

    PubMed Central

    Scanlon, Samantha A; Murray, Joseph A

    2011-01-01

    Celiac disease (CD) is an immune-mediated enteropathy triggered by exposure to wheat gluten and similar proteins found in rye and barley that affects genetically susceptible persons. This immune-mediated enteropathy is characterized by villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia. Once thought a disease that largely presented with malnourished children, the wide spectrum of disease activity is now better recognized and this has resulted in a shift in the presenting symptoms of most patients with CD. New advances in testing, both serologic and endoscopic, have dramatically increased the detection and diagnosis of CD. While the gluten-free diet is still the only treatment for CD, recent investigations have explored alternative approaches, including the use of altered nonimmunogenic wheat variants, enzymatic degradation of gluten, tissue transglutaminase inhibitors, induction of tolerance, and peptides to restore integrity to intestinal tight junctions. PMID:22235174

  16. Survival of childhood polycystic kidney disease following renal transplantation: the impact of advanced hepatobiliary disease.

    PubMed

    Davis, Ira D; Ho, Martin; Hupertz, Vera; Avner, Ellis D

    2003-10-01

    Childhood PKD encompasses the diagnoses of AR and ADPKD, glomerulocystic disease, and syndromes such as tuberous sclerosis or Jeune's syndrome. Given the fact that a majority of PKD children with ESRD carry the diagnosis of ARPKD, natural history studies assessing the long-term prognosis of PKD patients following renal transplantation must focus on morbidity and mortality issues related to complications from congenital hepatic fibrosis. Using the NAPRTCS registry, we analyzed the patient and graft survival rates of 203 PKD patients and 7044 non-PKD patients undergoing renal transplantation between 1987 and 2001. Deceased PKD patients, all with a diagnosis of ARPKD, were further identified and characterized using a special questionnaire submitted to the principal investigators. Overall graft and patient survival rates were not significantly different between PKD and non-PKD patients. No differences in rates of acute rejection or time to first rejection were noted between PKD and non-PKD patients. The relative risk of living longer than 3 yr in the PKD patients was not significantly different from non-PKD patients (RR = 0.70, p = 0.28). Sepsis was identified as a likely factor in the cause of death in nine (64%) ARPKD patients and was comfirmed with a positive blood culture in four patients. Despite similar graft and patient survival rates among PKD and non-PKD children following renal transplantation, our results suggest that ARPKD transplant recipients appear to be at increased risk for sepsis that may be related to hepatic fibrosis and ascending cholangitis. The utility of early liver transplantation in ARPKD patients with significant hepatobiliary disease is discussed.

  17. Chronic Chagas disease with advanced cardiac complications in Japan: Case report and literature review.

    PubMed

    Imai, Kazuo; Maeda, Takuya; Sayama, Yusuke; Osa, Morichika; Mikita, Kei; Kurane, Ichiro; Miyahira, Yasushi; Kawana, Akihiko; Miura, Sachio

    2015-10-01

    Due to the unprecedented recent increases in global migration, Chagas disease has become a global health threat and its epidemiology has drastically changed. Here we describe the first case in Japan of benznidazole treatment for chronic Chagas disease characterized by advanced cardiac complications. A 55-year-old Japanese-Brazilian woman who had previously presented with chronic heart failure was diagnosed as having Chagas disease and treated with benznidazole to prevent aggravation of her cardiac complications. However, benznidazole administration was stopped on day 56 due to severe drug-induced peripheral neuritis. Sixteen months later, her serologic test for Trypanosoma cruzi is still positive and she is being followed regularly by cardiology. Despite an estimated prevalence of over 4000 cases in Japan, only a few cases of Chagas disease have been reported. A Medline search revealed only 7 cases identified between 1995 and 2014 in Japan: in 6 cases, complications of chronic Chagas disease were apparent at the time of presentation, and sudden death occurred in 2 of these cases due to cardiac complications. This clinical case and literature review re-emphasize the urgent need to establish a surveillance network and improve the diagnostic methods and treatment framework for Chagas disease in Japan.

  18. Genetic polymorphism of N-acetyltransferases, glutathione S-transferase M1 and NAD(P)H:quinone oxidoreductase in relation to malignant and benign pancreatic disease risk. The International Pancreatic Disease Study Group.

    PubMed

    Bartsch, H; Malaveille, C; Lowenfels, A B; Maisonneuve, P; Hautefeuille, A; Boyle, P

    1998-06-01

    Carcinogens present in cigarette smoke and diet have been associated with pancreatic cancer. We hypothesized that heterocyclic and aromatic amines implicated in these exposures could be involved as causative agents and that therefore genetic variation in enzymes metabolizing these carcinogens could modify the risk of developing malignant and benign pancreatic disease. The effect of the genetic polymorphism of acetyltransferases (NAT1) and NAT2), glutathione S-transferase M1 (GSTM1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) on the risk of pancreatic diseases (cancer, pancreatitis) was examined in a case-control study. PCR-based assays were used for genotype analysis of genomic DNA from whole blood cells. Samples collected from Caucasian patients with diagnosed pancreatic cancer (n = 81), with non-alcoholic (n = 41) and alcoholic pancreatitis (n = 73) and from asymptomatic control subjects (n = 78) were analysed. The prevalence of GSTM1 null genotype and of NAT2 fast and slow acetylator genotypes and the distribution of frequencies for NQO1 genotypes did not differ in subjects with pancreatic diseases vs controls. For NAT1 slow acetylators a non-significant excess (P = 0.18) was found among pancreatic cancer cases vs controls. There was a significant over-representation of the GSTM1 AB or B genotype in all pancreatic disease cases combined (OR = 2.6; P < 0.05). When concurrent controls were pooled with literature controls (n = 1427), OR was 1.4 (P = 0.08). The results of this study, requiring confirmation, suggest that the polymorphism of GSTM1 and NAT1 enzymes may be associated with a modest increase in susceptibility to pancreatic diseases.

  19. Management of conjunctival malignant melanoma: a review and update

    PubMed Central

    Wong, James R.; Nanji, Afshan A.; Galor, Anat; Karp, Carol L.

    2014-01-01

    Conjunctival malignant melanoma is a pigmented lesion of the ocular surface. It is an uncommon but potentially devastating tumor that may invade the local tissues of the eye, spread systemically through lymphatic drainage and hematogenous spread, and recur in spite of treatment. Despite its severity, the rarity of available cases has limited the evidence for diagnosis and management. This review will provide an overview of the epidemiology, presentation, diagnosis, management, and surveillance of conjunctival melanoma, with an emphasis on recent advances in biological therapies to treat this disease. PMID:25580155

  20. [Current treatment strategy in malignant pleural effusion].

    PubMed

    Türler, A; Walter, M; Schmitz-Rixen, T

    1996-01-01

    Malignant pleural effusions are a grave consequence of advanced cancer disease. The successful suppression of pleural fluid reaccumulation can make a major contribution to the management and palliative care of patients with disseminated cancer. Many treatment concepts have been reported in the literature. The recommended therapy in malignant pleural effusions consists of intrapleural instillation of a sclerotic agent to produce pleurodesis. Different substances have been used, including tetracyclines, cytostatic agents, fibrin, talc, Corynebacterium parvum, cytokines and others. We reviewed the most frequently used techniques of pleurodesis in order to define the most effective treatment concept. In 15 prospective randomized trials the success rates varied from 13% with bleomycin to 100% with talc or Corynebacterium parvum. Talc was superior to other agents in 6 of 6, Corynebacterium parvum in 3 of 4 and bleomycin or tetracycline only in 3 of 8 studies. Adverse effects were frequently observed with cytostatic agents, but were very rare in the case of talc or fibrin instillation. Comparing the recently published data pleurodesis with talc appears to be the most effective treatment strategy, followed by Corynebacterium parvum, bleomycin and tetracycline. PMID:8686317

  1. The melanocortin 1 receptor (Mc1r) variants do not account for the co-occurrence of Parkinson's disease and malignant melanoma.

    PubMed

    Elincx-Benizri, Sandra; Inzelberg, Rivka; Greenbaum, Lior; Cohen, Oren S; Yahalom, Gilad; Laitman, Yael; Djaldetti, Ruth; Orlev, Yael; Scope, Alon; Azizi, Esther; Friedman, Eitan; Hassin-Baer, Sharon

    2014-12-01

    Parkinson's disease (PD) is characterized by loss of melanin-positive dopaminergic neurons in the substantia nigra. Malignant melanoma (MM), a melanocyte-derived neoplasm, occurs with higher than expected frequency among PD patients. Red-haired individuals exhibit a threefold risk for developing MM than dark-haired people; PD risk also increases with lighter hair color. One plausible explanation for the associations between MM, hair color, and PD is the melanocortin-1 receptor (MC1R) gene that plays a key role in hair and skin pigmentation as well as in MM predisposition. We hypothesized that specific MC1R variants may predispose to both MM and PD. Genotyping of the MC1R gene was performed for 16 PD patients with MM (PD+ MM+) and for three sets of age, sex, and ethnically matched controls, including 36 patients with PD (PD+ MM-), 37 with MM (PD- MM+) and 37 with neither diagnosis (PD- MM-). No association was found between MC1R variants and the co-occurrence of PD and MM. The risk for MM was higher in carriers of two MC1R variants versus with no MC1R variant (odds ratio (OR)=5.0, 95% confidence interval (CI) 1.7-14.4, p=0.003). The risk for PD in carriers of two MC1R variants was markedly lower (OR=0.213, 95% CI 0.063-0.725) compared with individuals with no MC1R variant (p=0.013). In this study, MC1R variants were not associated with both MM and PD. Further studies in larger cohorts are necessary to confirm these preliminary results. PMID:25284244

  2. Long-Term Stable Mixed Chimerism after Hematopoietic Stem Cell Transplantation in Patients with Non-Malignant Disease, Shall We Be Tolerant?

    PubMed Central

    Stikvoort, Arwen; Sundin, Mikael; Uzunel, Mehmet; Gertow, Jens; Sundberg, Berit; Schaffer, Marie; Mattsson, Jonas; Uhlin, Michael

    2016-01-01

    Long-term stable mixed chimerism is a rare and poorly understood phenomenon post hematopoietic stem cell transplantation. This study aims to shed light on whether the two hematopoietic systems in patients with mixed chimerism remain functional. Additionally, we investigate possible immunologic differences in these individuals compared to patients with only donor derived immune cells. Patients with donor and mixed chimerism, at median 10 (5–16) years post-HSCT for non-malignant diseases, were assessed regarding clinical situation and immune system (phenotypical and functional). No difference in long-term outcome was seen in terms of general wellbeing, central phenotypic immune system features (e.g., differentiation status, CD4/CD8 ratio, B and NK-cell frequency) and antibody responses to immunizations. At a median of 10 years post transplantation, patients with mixed chimerism had significantly higher IgG3 and platelet levels. Additionally, these patients had higher NKT-cell levels (CD94+CD8+ and CD56+CD8+) than patients with donor chimerism. In depth phenotypic analysis of patients with mixed chimerism demonstrated recipient-derived fractions in most immune cell lineages (e.g., T-cell, B-cell and NK-cell subsets). Recipient cells were also capable of responding to mitogenic stimulation with production of several cytokines. In conclusion, long-term mixed chimerism did not negatively affect patient wellbeing and long-term outcome. Moreover, recipient-derived immunity may still be functional in these patients, suggesting an active state of tolerance and immunologic dependence on both hematopoietic systems. PMID:27152621

  3. Immunotherapy of malignant disease with tumor antigen (TA)-specific monoclonal antibodies: does its therapeutic efficacy require cooperation with TA-specific CTL?

    PubMed Central

    Campoli, Michael; Ferris, Robert; Ferrone, Soldano; Wang, Xinhui

    2009-01-01

    A few tumor antigen (TA)-specific monoclonal antibodies (mAb) have been approved by FDA for the treatment of several major malignant diseases and are commercially available. Once in the clinic, mAb have an average success rate of ~30% and are well tolerated. These results have changed the face of cancer therapy, bringing us closer to more specific and more effective biologic therapy of cancer. The challenge facing tumor immunologists at present is represented by the identification of the mechanism(s) underlying patients’ differential clinical response to mAb-based immunotherapy. This information is expected to lead to the development of criteria to select patients to be treated with mAb-based immunotherapy. In the past in vitro and in vivo evidence has shown that TA-specific mAb can mediate their therapeutic effect by inducing tumor cell apoptosis, inhibiting the targeted antigen function, blocking tumor cell signaling and/or mediating complement-or cell-dependent lysis of tumor cells. More recent evidence suggests that TA-specific mAb can induce TA-specific cytotoxic T cell responses by enhancing TA uptake by dendritic cells (DC) and cross-priming of T cells. In this manuscript, we briefly summarize the TA-specific mAb that have received FDA approval. Next we review the potential mechanisms underlying the therapeutic efficacy of TA-specific mAb with emphasis on the induction of TA-specific cellular immune responses and their potential to contribute to the clinical efficacy of TA-specific mAb-based immunotherapy. Lastly, we discuss the potential negative impact of immune escape mechanisms on the clinical efficacy of TA-specific mAb-based immunotherapy. PMID:20028761

  4. Long-Term Stable Mixed Chimerism after Hematopoietic Stem Cell Transplantation in Patients with Non-Malignant Disease, Shall We Be Tolerant?

    PubMed

    Stikvoort, Arwen; Sundin, Mikael; Uzunel, Mehmet; Gertow, Jens; Sundberg, Berit; Schaffer, Marie; Mattsson, Jonas; Uhlin, Michael

    2016-01-01

    Long-term stable mixed chimerism is a rare and poorly understood phenomenon post hematopoietic stem cell transplantation. This study aims to shed light on whether the two hematopoietic systems in patients with mixed chimerism remain functional. Additionally, we investigate possible immunologic differences in these individuals compared to patients with only donor derived immune cells. Patients with donor and mixed chimerism, at median 10 (5-16) years post-HSCT for non-malignant diseases, were assessed regarding clinical situation and immune system (phenotypical and functional). No difference in long-term outcome was seen in terms of general wellbeing, central phenotypic immune system features (e.g., differentiation status, CD4/CD8 ratio, B and NK-cell frequency) and antibody responses to immunizations. At a median of 10 years post transplantation, patients with mixed chimerism had significantly higher IgG3 and platelet levels. Additionally, these patients had higher NKT-cell levels (CD94+CD8+ and CD56+CD8+) than patients with donor chimerism. In depth phenotypic analysis of patients with mixed chimerism demonstrated recipient-derived fractions in most immune cell lineages (e.g., T-cell, B-cell and NK-cell subsets). Recipient cells were also capable of responding to mitogenic stimulation with production of several cytokines. In conclusion, long-term mixed chimerism did not negatively affect patient wellbeing and long-term outcome. Moreover, recipient-derived immunity may still be functional in these patients, suggesting an active state of tolerance and immunologic dependence on both hematopoietic systems.

  5. Long-Term Stable Mixed Chimerism after Hematopoietic Stem Cell Transplantation in Patients with Non-Malignant Disease, Shall We Be Tolerant?

    PubMed

    Stikvoort, Arwen; Sundin, Mikael; Uzunel, Mehmet; Gertow, Jens; Sundberg, Berit; Schaffer, Marie; Mattsson, Jonas; Uhlin, Michael

    2016-01-01

    Long-term stable mixed chimerism is a rare and poorly understood phenomenon post hematopoietic stem cell transplantation. This study aims to shed light on whether the two hematopoietic systems in patients with mixed chimerism remain functional. Additionally, we investigate possible immunologic differences in these individuals compared to patients with only donor derived immune cells. Patients with donor and mixed chimerism, at median 10 (5-16) years post-HSCT for non-malignant diseases, were assessed regarding clinical situation and immune system (phenotypical and functional). No difference in long-term outcome was seen in terms of general wellbeing, central phenotypic immune system features (e.g., differentiation status, CD4/CD8 ratio, B and NK-cell frequency) and antibody responses to immunizations. At a median of 10 years post transplantation, patients with mixed chimerism had significantly higher IgG3 and platelet levels. Additionally, these patients had higher NKT-cell levels (CD94+CD8+ and CD56+CD8+) than patients with donor chimerism. In depth phenotypic analysis of patients with mixed chimerism demonstrated recipient-derived fractions in most immune cell lineages (e.g., T-cell, B-cell and NK-cell subsets). Recipient cells were also capable of responding to mitogenic stimulation with production of several cytokines. In conclusion, long-term mixed chimerism did not negatively affect patient wellbeing and long-term outcome. Moreover, recipient-derived immunity may still be functional in these patients, suggesting an active state of tolerance and immunologic dependence on both hematopoietic systems. PMID:27152621

  6. Strategies to Circumvent Testosterone Surge and Disease Flare in Advanced Prostate Cancer: Emerging Treatment Paradigms.

    PubMed

    Pokuri, Venkata K; Nourkeyhani, Houman; Betsy, Bodie; Herbst, Laurie; Sikorski, Marcus; Spangenthal, Edward; Fabiano, Andrew; George, Saby

    2015-07-01

    The testosterone surge and disease flare is a feared complication from initiation of gonadotropin-releasing hormone (GnRH) agonist treatment in advanced prostate adenocarcinoma. It is a common practice to start an average 7-day pretreatment regimen with an antiandrogen agent before initiating GnRH agonist therapy, to circumvent disease flare from testosterone surge. However, this might not be the best strategy and can be harmful, especially in patients at high risk of imminent organ damage from minimal testosterone surge. Surgical castration is a simple and cost-effective method that should be considered in these scenarios. But most patients refuse this procedure because of the permanent and psychologic impact of surgery. Novel GnRH antagonists, such as degarelix, and cytochrome P450 17 (CYP17) enzyme inhibitors, such as ketoconazole, achieve castrate-equivalent serum testosterone levels much faster than traditional GnRH agonists without the need for coadministration of antiandrogens. This article reports on 3 cases of impending oncologic emergencies in advanced prostate adenocarcinoma treated promptly with degarelix and ketoconazole without any disease flare related to testosterone surge. In the setting of symptomatic hormone-naïve metastatic prostate cancer, the authors suggest clinical trials using abiraterone, orteronel, and other newer agents that target the CYP17 axis (eg, ketoconazole) for fine-tuning the emergent medical castration methods and avoiding the dangers from the flare phenomenon.

  7. Advances and challenges in biosensor-based diagnosis of infectious diseases

    PubMed Central

    Sin, Mandy LY; Mach, Kathleen E; Wong, Pak Kin; Liao, Joseph C

    2014-01-01

    Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings. PMID:24524681

  8. [Efficacy and safety of selective estrogen receptor modulators in patients with advanced chronic kidney disease].

    PubMed

    Nakai, Kentaro

    2016-09-01

    Selective estrogen receptor modulators(SERMs)have beneficial effects on the improvement of bone mineral density of the spine and hip, and decrease the vertebral fracture in postmenopausal women. Similar to patients with advanced chronic kidney disease, including dialysis patients, however, SERMs cannot decrease the risk of hip fracture, which is extremely high in Japanese dialysis patients. One of the most important disadvantages of SERMs is an increase in the risk of venous thromboembolic events and fatal stroke in high-risk groups of the Framingham Stroke Risk Score. On the other hand, SERMs may be used in unique osteoporosis drugs for reducing the incidence and progression of breast cancer. Moreover, SERMs attenuate oxidative stress and may lessen the deterioration of kidney function in patients with chronic kidney disease. The evidences for the efficacy and safety of SERMs in patients with advanced chronic kidney disease are insufficient, and knowledge concerning the selection and indication of osteoporosis drugs for those patients need to be developed. PMID:27561348

  9. Glycated albumin is the preferred marker for assessing glycaemic control in advanced chronic kidney disease.

    PubMed

    Vos, Frederiek E; Schollum, John B; Walker, Robert J

    2011-12-01

    Diabetic nephropathy is the most common aetiology of end-stage kidney disease (ESKD). Strict glycaemic control reduces the development and progression of diabetes-related complications, and there is evidence that improved metabolic control improves outcomes in diabetic subjects with advanced chronic kidney disease (CKD). Glycaemic control in people with kidney disease is complex. Changes in glucose and insulin homeostasis may occur as a consequence of loss of kidney function and dialysis. The reliability of measures of long-term glycaemic control is affected by CKD and the accuracy of glycated haemoglobin (HbA1c) in the setting of CKD and ESKD is questioned. Despite the altered character of diabetes in CKD, current guidelines for diabetes management are not specifically adjusted to this patient group. The validity of indicators of longer term glycaemic control has been the focus of increased recent research. This review discusses the current understanding of commonly used indicators of metabolic control (HbA1c, fructosamine, glycated albumin) in the setting of advanced CKD (Stages 4 and 5, glomerular filtration rate <30 mL/min/1.73m(2)).

  10. Is gardening a stimulating activity for people with advanced Huntington's disease?

    PubMed

    Spring, Josephine A; Viera, Marc; Bowen, Ceri; Marsh, Nicola

    2014-11-01

    This study evaluated adapted gardening as an activity for people with advanced Huntington's disease (HD) and explored its therapeutic aspects. Visitors and staff completed a questionnaire and participated in structured interviews to capture further information, whereas a pictorial questionnaire was designed for residents with communication difficulties. Staff reported that gardening was a constructive, outdoor activity that promoted social interaction, physical activity including functional movement and posed cognitive challenges. Half the staff thought the activity was problem free and a third used the garden for therapy. Visitors used the garden to meet with residents socially. Despite their disabilities, HD clients enjoyed growing flourishing flowers and vegetables, labelling plants, being outside in the sun and the quiet of the garden. The garden is valued by all three groups. The study demonstrates the adapted method of gardening is a stimulating and enjoyable activity for people with advanced HD.

  11. Inflammation Biomarkers of Advanced Disease in Nongingival Tissues of Chronic Periodontitis Patients

    PubMed Central

    da Costa, Thiago Alvares; Silva, Marcelo José Barbosa; Alves, Polyanna Miranda; Chica, Javier Emílio Lazo; Barcelos, Emilio Zorzo; Giani, Max Antonio Alves; Garlet, Gustavo Pompermaier; da Silva, João Santana; Rodrigues Júnior, Virmondes; Rodrigues, Denise Bertulucci Rocha; Cardoso, Cristina Ribeiro de Barros

    2015-01-01

    Chronic periodontitis is a multifactorial inflammatory disease that affects supporting structures of the teeth. Although the gingival response is largely described, little is known about the immune changes in the alveolar bone and neighboring tissues that could indicate periodontal disease (PD) activity. Then, in this study we identified the ongoing inflammatory changes and novel biomarkers for periodontitis in the tissues directly affected by the destructive disease in PD patients. Samples were collected by osteotomy in 17 control subjects during extraction of third molars and 18 patients with advanced PD, in which alveoloplasty was necessary after extraction of teeth with previous extensive periodontal damage. Patients presented mononuclear cells infiltration in the connective tissue next to the bone and higher fibrosis area, along with increased accumulation of IL-17+ and TRAP+ cells. The levels of TNF-α and MMP-2 mRNA were also elevated compared to controls and a positive and significant correlation was observed between TNF-α and MMP-2 mRNA expression, considering all samples evaluated. In conclusion, nongingival tissues neighboring large periodontal pockets present inflammatory markers that could predict ongoing bone resorption and disease spreading. Therefore, we suggested that the detailed evaluation of these regions could be of great importance to the assessment of disease progression. PMID:26063981

  12. Long-term levodopa/carbidopa intestinal gel in advanced Parkinson's disease.

    PubMed

    Cáceres-Redondo, María T; Carrillo, Fátima; Lama, María J; Huertas-Fernández, Ismael; Vargas-González, Laura; Carballo, Manuel; Mir, Pablo

    2014-03-01

    The short-term benefits of levodopa/carbidopa intestinal gel (LCIG) in patients with advanced Parkinson's disease (PD) are well documented, but the long-term benefits are still uncertain. The aim of this study was to investigate the motor and cognitive outcome of LCIG treatment in advanced PD after a follow-up period of at least 24 months. We assessed 29 patients with advanced PD who started LCIG infusion at our centre between 2007 and 2013. Motor fluctuations, parkinsonian symptoms, activities of daily living and impact on quality of life were evaluated. We also investigated the cognitive outcome using a battery of neuropsychological tests. All adverse events were recorded. Of the 29 PD patients who initiated LCIG, 16 patients reached the follow-up evaluation (24 months), after a mean time period of 32.2 ± 12.4 months. Six patients did not fulfil the 24-month follow-up visit and were evaluated after a mean time period of 8.6 ± 5.4 months. Seven patients discontinued the treatment before the scheduled visit. "Off" time and "On" dyskinesia duration were significantly reduced. LCIG improved quality of life and non motor symptoms, despite overall unchanged total levodopa doses prior to LCIG beginning. Motor and cognitive decline were detected. A relatively high number of adverse events occurred during the follow-up, above all, technical problems with the infusion device and mild problems related with gastrostomy. There were four cases of peripheral neuropathy (PN), 2 of which were considered serious. Our data confirm that LCIG is beneficial in the long-term treatment of advanced PD patients despite a decline in cognitive functions in a subgroup of patients, probably due to disease progression. PN in patients with LCIG may be more frequent than the published date suggest. PMID:24477490

  13. Pleural malignancies including mesothelioma.

    PubMed

    Hillerdal, G

    1995-07-01

    Malignant mesothelioma is caused almost exclusively by occupational exposure to asbestos. During the past few years, however, increasing evidence has mounted that background exposure to asbestos could be sufficient to cause mesothelioma. Treatment of malignant mesothelioma remains a big problem. Some new approaches are on their way, and the most exciting ones are local immunotherapy in very early cases. Some success has been reported with local interferon treatment. As for treatment of metastatic pleural disease, the main purpose is symptomatic relief of dyspnea caused by fluid accumulation. The best way to achieve a lasting palliation is pleurodesis, and the most common way to do this, is by chemical means. The drug of choice in the United States has for many years been tetracycline, but since injectable tetracycline is no longer available, some substitute must be found. The substance that will "win" is not yet clear, but the two leading contestants are talc and doxycycline. Bleomycin also has its supporters, and a dark horse is quinacrine, which although not easily available in the United States, has been used in many European centers for decades. PMID:9363074

  14. Unified Huntington's disease rating scale for advanced patients: validation and follow-up study.

    PubMed

    Youssov, Katia; Dolbeau, Guillaume; Maison, Patrick; Boissé, Marie-Françoise; Cleret de Langavant, Laurent; Roos, Raymund A C; Bachoud-Lévi, Anne-Catherine

    2013-10-01

    The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In advanced patients, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP), in order to improve longitudinal assessment of patients at advanced disease stage. Sixty-nine patients with a Total Functional Capacity (TFC)  ≤  5 were recruited in France and in the Netherlands. Among them, 45 patients were followed longitudinally (mean 1.6  ±  1.2 years) with the UHDRS-FAP; 30 were also assessed with the UHDRS. Cross-sectional analyses evaluated psychometric properties and interrater reliability of the scale. Longitudinal analyses evaluated the sensitivity to decline compared to the UHDRS. Internal consistency was higher for motor and cognitive scores than for somatic and behavioral scores (0.84, 0.91, 0.70, and 0.49, respectively). Interrater reliability was  ≥  0.88 in all scores. The somatic score, specific to the UHDRS-FAP, declined over time, as well as motor and cognitive performance with both scales. Although performance with the 2 scales correlated, the UHDRS-FAP appeared more sensitive to change and was the only scale that detected decline in patients with a TFC  ≤  1. Neither scale detected a significant decline in behavioral scores. The UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items relevant for daily care. Behavioral scores tended to decline but this may reflect the decline in the communicative abilities of the patients.

  15. The unified Huntington's Disease Rating Scale for advanced patients: validation and follow-up study.

    PubMed

    Youssov, Katia; Dolbeau, Guillaume; Maison, Patrick; Boissé, Marie-Françoise; Cleret de Langavant, Laurent; Roos, Raymund A C; Bachoud-Lévi, Anne-Catherine

    2013-12-01

    The Unified Huntington's Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntington's disease (HD). In patients with advanced HD, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS-For Advanced Patients (UHDRS-FAP) to improve longitudinal assessment of patients at the advanced disease stage. Sixty-nine patients with a Total Functional Capacity score ≤ 5 were recruited in France and the Netherlands. Among them, 45 patients were followed longitudinally (mean ± standard deviation, 1.6 ± 1.2 years) with the UHDRS-FAP; 30 patients also were assessed with the UHDRS. In cross-sectional analyses, the psychometric properties and inter-rater reliability of the scale were evaluated. Longitudinal analyses were used to evaluate the sensitivity to decline of the UHDRS-FAP compared with the UHDRS. Internal consistency was higher for motor (0.84) and cognitive (0.91) scores than for somatic (0.70) and behavioral (0.49) scores. Inter-rater reliability was ≥ 0.88 for all scores. The somatic score, which was specific to the UHDRS-FAP, declined over time along with motor and cognitive performance on both scales. Although performance with the two scales was correlated, the UHDRS-FAP appeared to be more sensitive to change and was the only scale that detected decline in patients with a Total Functional Capacity score ≤ 1. Neither scale detected a significant decline in behavioral scores. The results indicate that the UHDRS-FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items that are relevant for daily care. Behavioral scores tended to decline, but this may reflect the decline in patients' communicative abilities.

  16. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD. PMID:25786448

  17. Advancing Alzheimer's disease diagnosis, treatment, and care: recommendations from the Ware Invitational Summit.

    PubMed

    Naylor, Mary D; Karlawish, Jason H; Arnold, Steven E; Khachaturian, Ara S; Khachaturian, Zaven S; Lee, Virginia M-Y; Baumgart, Matthew; Banerjee, Sube; Beck, Cornelia; Blennow, Kaj; Brookmeyer, Ron; Brunden, Kurt R; Buckwalter, Kathleen C; Comer, Meryl; Covinsky, Kenneth; Feinberg, Lynn Friss; Frisoni, Giovanni; Green, Colin; Guimaraes, Renato Maia; Gwyther, Lisa P; Hefti, Franz F; Hutton, Michael; Kawas, Claudia; Kent, David M; Kuller, Lewis; Langa, Kenneth M; Mahley, Robert W; Maslow, Katie; Masters, Colin L; Meier, Diane E; Neumann, Peter J; Paul, Steven M; Petersen, Ronald C; Sager, Mark A; Sano, Mary; Schenk, Dale; Soares, Holly; Sperling, Reisa A; Stahl, Sidney M; van Deerlin, Vivianna; Stern, Yaakov; Weir, David; Wolk, David A; Trojanowski, John Q

    2012-09-01

    To address the pending public health crisis due to Alzheimer's disease (AD) and related neurodegenerative disorders, the Marian S. Ware Alzheimer Program at the University of Pennsylvania held a meeting entitled "State of the Science Conference on the Advancement of Alzheimer's Diagnosis, Treatment and Care," on June 21-22, 2012. The meeting comprised four workgroups focusing on Biomarkers; Clinical Care and Health Services Research; Drug Development; and Health Economics, Policy, and Ethics. The workgroups shared, discussed, and compiled an integrated set of priorities, recommendations, and action plans, which are presented in this article. PMID:22959699

  18. Advances in methodology and current prospects for primary drug therapies for Alzheimer's disease.

    PubMed

    Knopman, D S

    2000-01-01

    There has been gratifying progress in the development of drugs for Alzheimer's disease (AD). Even though the current generation of medications, the cholinesterase inhibitors (CEIs), has produced only modest benefits, our concept of an "effective" therapy has matured considerably over this time. A less visible but equally important advance has been a quantum leap in expertise in clinical trial methodology. This chapter reviews the methodological underpinnings of clinical trials in AD: patient selection issues, key design issues, and an overview of currently available agents and the prospects for drugs of the future.

  19. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD.

  20. Percutaneous minimally invasive treatment of malignant biliary strictures: current status.