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Sample records for advanced malignant disease

  1. Chemotherapy in advanced malignant diseases in Iraq

    PubMed Central

    Talib, Hussein

    1971-01-01

    This work discusses the experience of one surgical team in the Third Surgical Unit at the Republican Teaching Hospital, Baghdad, from 1967 to 1970. 112 patients with advanced malignant lesions in various parts of the body were dealt with. In 84, the intra-arterial route was adopted; in the remaining, systemic administration of cytotoxic agents either singly or in combination was employed. The results are reported in terms of subjective and objective response, and the various complications are discussed. ImagesFig. 1Fig. 2 PMID:5137574

  2. [Phase-II-study with vindesine (desacetyl-vinblastine-amide-sulfate) in advanced malignant diseases].

    PubMed

    Goldhirsch, A; Beer, M; Sonntag, R W; Tschopp, L; Cavalli, F; Ryssel, H J; Brunner, K W

    1980-07-08

    53 patients with advanced and measurable cancerr were treated with vindesine in doses of 3 mg/m2 (pretreated) and 4 mg/m2 (non pretreated) i.v. once weekly. 48 patients are evaluable for response: of 14 patients with squamous cell carcinoma of the lung, 1 partial remission (PR), 1 minor response (MR) and 1 no change (NC) were observed. In 5 patients with large cell carcinoma of the lung: 1 NC. In 3 with adenocarcinoma of the lung: 1 MR. One patient with nasopharyngeal carcinoma had progressive disease. Stable disease was observed in a patient with carcinoma of the tongue and in a patient with adenocarcinoma of the esophagus. Four patients with colorectal carcinoma had progressive disease. One MR was observed in a patient with breast cancer, while all of the other 3 patients had progressive disease. One carcinoma of the penis was stable. One MR was observed in a patient with Hodgkin's disease. One PR was observed in a case with no-Hodgkin's lymphoma. A patient with acute leukemia had progressive disease. Among 9 patients with malignant melanoma, 3 had an MR and 1 patient had stable disease. A patient with fibrosarcoma had progressive disease. Observed toxicity included leukopenia, thrombocytopenia, anemia, paresthesias, constipation, jaw pain, nausea, stomatitis, alopecia, loss of taste, pruritus and skin rash, weakness and fatigue.

  3. 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

  4. Phase I evaluation of recombinant interleukin-2 in patients with advanced malignant disease.

    PubMed

    Atkins, M B; Gould, J A; Allegretta, M; Li, J J; Dempsey, R A; Rudders, R A; Parkinson, D R; Reichlin, S; Mier, J W

    1986-09-01

    Seventeen patients with refractory malignant tumors were treated with recombinant human interleukin-2 (IL-2) administered by weekly bolus intravenous (IV) injection in a phase I dose escalation trial. Patients received 10,000 to 1,000,000 U/m2 per injection over a course of 3 to 33 weeks. Toxicity was dose related and consisted primarily of fever, chills, nausea, and vomiting. Hypotension was observed at doses of 500,000 U/m2 or higher and in one instance was sufficiently severe to require pressors. No tumor regression was seen and all patients eventually developed progressive disease. Blood levels of cortisol, ACTH, prolactin, and growth hormone as well as the acute phase reactant C-reactive protein (CRP) increased after the administration of IL-2 in most patients. Serum IL-2 levels in excess of 250 U/mL were detected five minutes after an IV injection of 1,000,000 U/m2, after which the levels declined with a half-life of approximately 25 minutes. No alteration in lymphocyte surface phenotype or enhancement in natural cell-mediated cytotoxicity against natural killer (NK)-sensitive and resistant tumor cell lines was observed when these parameters were measured weekly just before the IL-2 injections. However, a dramatic but transient decline in circulating lymphocytes and NK activity was noted within hours of receiving IL-2. This effect was independent of fever and was not abrogated by pretreatment with ibuprofen or metyrapone. The majority of patients developed serum IgG antibodies of IL-2 detectable with a sensitive enzyme-linked immunosorbent assay (ELISA) and a nitrocellulose dot blot assay. The development of anti-IL-2 antibodies was not associated with symptoms suggestive of serum sickness, reductions in serum complement levels, or deterioration in lymphocyte tumoricidal activity. This investigation provides insight into the in vivo actions of this potent biological response modifier and will assist in the design of future studies with IL-2 administered alone

  5. Advances in the management of malignant mesothelioma.

    PubMed

    Khalil, Mazen Y; Mapa, Marissa; Shin, Hyung Ju C; Shin, Dong M

    2003-07-01

    Malignant mesotheliomas are very aggressive tumors that originate from mesothelial cells, which form the serosal lining of the pleura, pericardial, and peritoneal cavities. Finding effective chemotherapeutic treatment for malignant mesothelioma is a challenge. There is no standard treatment because this tumor is relatively resistant to therapy. A resurgence of interest has been expressed in novel therapies and conventional treatments used in different ways. Several treatment modalities have been studied, including chemotherapy, radiotherapy, surgery, and immunotherapy. Chemotherapy can be administered systemically or directly into the pleura. This review presents the results of the most recent trials and highlights the most promising advances in the battle against this aggressive disease.

  6. 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

  7. 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

  8. Endoscopic laser palliation for advanced malignant dysphagia.

    PubMed Central

    Bown, S G; Hawes, R; Matthewson, K; Swain, C P; Barr, H; Boulos, P B; Clark, C G

    1987-01-01

    Palliative treatment of malignant dysphagia aims to optimise swallowing for the maximum time possible with the minimum of general distress to these seriously ill patients. Thirty four patients considered unsuitable for surgery because of advanced malignancy, other major pathology or in whom previous surgery had been unsuccessful were treated endoscopically with the Nd YAG laser. Significant improvement was achieved in 29 (85%). On a scale of 0-4 (0 = normal swallowing; 4 = dysphagia for all fluids), mean improvement was 1.7, with 25 patients (74%) able to swallow most, or all solids after treatment. With increasing experience, the average number of treatment sessions required for each patient became less; initial time in hospital became comparable to that needed for intubation. Failures were caused by inappropriate patient selection (3), or laser related perforation (2). The mean survival in the whole group was 19 weeks (range 2-44). Eighteen patients needed further treatment for recurrent dysphagia, a mean of six weeks (range 2-15) after initial therapy. Ten of these responded, but eight eventually required insertion of a prosthetic tube. The duration of good palliation was very variable after initial laser therapy. Images Fig. 3 PMID:2443431

  9. 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

  10. Palliation of advanced pelvic malignant disease with large fraction pelvic radiation and misonidazole: final report of RTOG phase I/II study

    SciTech Connect

    Spanos, W.J. Jr.; Wasserman, T.; Meoz, R.; Sala, J.; Kong, J.; Stetz, J.

    1987-10-01

    Between October 1979 and June 1982 forty-six patients were entered on a non-randomized Phase I-II protocol for the evaluation of Misonidazole combined with high dose per fraction radiation for the treatment of advanced pelvic malignancies. Pelvic radiation consisted of 1000 cGy in one fraction repeated at 4-week intervals for a total of three treatments. Oral Misonidazole at a dose of 4 gm/m2 was administered 4-6 hr prior to radiation (total dose 12 g/m2). The distribution of histology consisted of 20 gynecologic, 24 bowel, and 2 prostate malignancies. Of the thirty-seven patients completing the three treatments; there were 6 complete responses (14% CR), 10 partial responses (27% PR) 19 minimal or no response (32% NR), and 4 unevaluable. One patient remains NED 5.5 years following radiation. Toxicity directly related to Misonidazole was minimal and consisted primarily of transcient Grade 1, 2 peripheral neuropathy (20% Grade 1, 4% Grade 2) and Grade 2 ototoxicity (4%). Radiation toxicity was significant for late bowel damage. There were 4 (11%) Grade 3 and 7 (19%) Grade 4 gastro-intestinal (GI) toxicities. Kaplan-Meier plot of GI toxicity showed a progressive increase in incidence with time for projected rate of 49% Grade 3, 4 by 12-month. GI toxicity (Grade 3, 4) was also related to tumor response. The complication rate was 80% (4/6) for CR, 30% (3/10) for PR and 26% (5/19) for NR or progression. Because of the GI complication rate, this protocol for palliation of advanced pelvic malignancies has been replaced by a protocol that uses 4 fractions over 2 days (b.i.d.) of 370 cGy per fraction repeated at 3-week intervals for a total of 3 courses.

  11. [Advances in cellular immunotherapy for malignant melanoma].

    PubMed

    López, Mercedes; Escobar, Alejandro; Alfaro, Jorge; Fodor, Miguel; Larrondo, Milton; Ferrada, Carlos; Salazar-Onfray, Flavio

    2004-09-01

    An alternative strategy for cancer treatment is the manipulation of the immune system, denominated cancer immunotherapy. The immunotherapeutical use of cells of the immune system, like dendritic cells (DC), is being explored in different clinical protocols. Recently, we finalized a clinical phase I protocol, for the treatment of malignant melanoma, using DCs loaded with tumor lysates. Our results indicate that the subcutaneous application of DCs do not produce adverse effects. We also observed an increase of tumor specific T lymphocytes precursors in the blood, associated to hypersensitivity reactions (DTH) in 60% of the treated patients. In most cases, an stability in the disease was observed, although without a significant association between vaccination and survival. Additionally, therapies based on Interleukin-2 (IL-2) have been used with relative success in the treatment of some kind of tumors since 1985. However, problems associated to the toxicity of IL-2 still restrict its massive use. Our direct experience with the use of IL-2, indicates that low doses and its subcutaneous application, maintains the beneficial effects for patients, eliminating the adverse effects. Based on the accumulated evidence during last the five years, we decided to implement an optimized clinical protocol, which alternatively combines dendritic cells vaccines with the use of low doses of IL-2 for the reinforcement of the immunological system.

  12. Advances in the treatment of hematologic malignancies using immunoconjugates

    PubMed Central

    Palanca-Wessels, Maria Corinna

    2014-01-01

    Monoclonal antibody therapy has revolutionized cancer treatment by significantly improving patient survival both in solid tumors and hematologic malignancies. Recent technological advances have increased the effectiveness of immunotherapy leading to its broader application in diverse treatment settings. Immunoconjugates (ICs) consist of a cytotoxic effector covalently linked to a monoclonal antibody that enables the targeted delivery of its therapeutic payload to tumors based on cell-surface receptor recognition. ICs are classified into 3 groups based on their effector type: immunotoxins (protein toxin), radioimmunoconjugates (radionuclide), and antibody drug conjugates (small-molecule drug). Optimization of each individual component of an IC (antibody, linker, and effector) is essential for therapeutic efficacy. Clinical trials have been conducted to investigate the effectiveness of ICs in hematologic malignancies both as monotherapy and in multiagent regimens in relapsed/refractory disease as well as frontline settings. These studies have yielded encouraging results particularly in lymphoma. ICs comprise an exciting group of therapeutics that promise to play an increasingly important role in the management of hematologic malignancies. PMID:24578502

  13. Systemic sarcoidosis mimicking malignant metastatic disease

    PubMed Central

    Hammen, Irena; Sherson, David Lee; Davidsen, Jesper Roemhild

    2015-01-01

    We present a case of systemic sarcoidosis involving the liver, pancreas, lungs, mediastinal and intraabdominal lymph nodes and bones. Multiple organ system manifestations mimicked malignant metastatic disease. The diagnosis was established with clinical, radiological, and pathological findings after neoplasm was ruled out by pathological tests. The patient showed rapid symptom remission with systemic steroid treatment. PMID:26672956

  14. Cutaneous Manifestations of Internal Malignant Disease

    PubMed Central

    McLean, David I.

    1987-01-01

    The skin can provide clues to the well-being of our patients. Some skin changes, such as hypertrichosis lanuginosa acquisita or erythema gyratum repens, are so specific that there is a virtual certainty of internal malignancy. Other changes, such as severe pruritus, are significant management problems in late-stage lymphoma and leukemia. Still others, such as herpes zoster in a cancer patient in remission, may be a marker for recurrent malignant disease. This review will discuss many of the skin changes associated with systemic cancer. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:21263960

  15. Plastic biliary stents for malignant biliary diseases.

    PubMed

    Huibregtse, Inge; Fockens, Paul

    2011-07-01

    Plastic biliary endoprostheses have not changed much since their introduction more than 3 decades ago. Although their use has been challenged by the introduction of metal stents, plastic stents still remain commonly used. Much work has been done to improve the problem of stent obstruction but without substantial clinical success. In this review, the authors discuss the history of plastic biliary stent development and the current use of plastic stents for malignant biliary diseases.

  16. 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

  17. Pigmented mammary paget disease misdiagnosed as malignant melanoma.

    PubMed

    Lee, Ji Hye; Kim, Tae Hyung; Kim, Soo-Chan; Kim, You Chan; Roh, Mi Ryung

    2014-12-01

    Pigmented mammary Paget disease is a very rare clinicopathologic variant of mammary Paget disease. Diagnosis is often difficult because its clinical and histological features are very similar to those of malignant melanoma. Herein, we report a case of pigmented mammary Paget disease misdiagnosed as malignant melanoma.

  18. Serum fucose level in malignant diseases.

    PubMed

    Sawke, N G; Sawke, G K

    2010-01-01

    We review the present knowledge of serum fucose with special attention to its relation with various malignant diseases. We summarize the role of serum fucose as a useful diagnostic and prognostic marker when used singly or in combination. The purpose of this review is to provide an expert opinion on the practical and applied aspect of serum fucose level in clinical practice and research settings. Our review is based on information from published research studies, library books, and electronic searches through Medline and PubMed. The available published data were used as the basis for recommendations. Each of the subsections concludes to provide information to assist the clinicians and the research scientists make informed decisions.

  19. Antisense oligonucleotides as therapeutics for malignant diseases.

    PubMed

    Ho, P T; Parkinson, D R

    1997-04-01

    The continued progress in our understanding of the biology of neoplasia and in the identification, cloning, and sequencing of genes critical to tumor cell function permits the exploitation of this information to develop specific agents that may directly modulate the function of these genes or their protein products. Antisense oligonucleotides are being investigated as a potential therapeutic modality that takes direct advantage of molecular sequencing. The antisense approach uses short oligonucleotides designed to hybridize to a target mRNA transcript through Watson-Crick base pairing. The formation of this oligonucleotide: RNA heteroduplex results in mRNA inactivation and consequent inhibition of synthesis of the protein product. A fundamental attraction of the antisense approach is that this method potentially may be applied to any gene product, in theory, for the treatment of malignant and non-malignant diseases. However, this simple and attractive model has proven to be much more complex in practice. A number of important challenges in the preclinical development of antisense oligonucleotides have been identified, including stability, sequence length, cellular uptake, target sequence selection, appropriate negative controls, oligonucleotide: protein interactions, and cost of manufacture. Although the biological activity of an oligonucleotide against its molecular target is theoretically sequence-dependent, the animal pharmacokinetics and toxicology of phosphorothioate analogues directed against vastly disparate gene products appear relatively non-sequence-specific. In oncology, a number of clinical trials have been initiated with antisense oligonucleotides directed against molecular targets including: p53; bcl-2; raf kinase; protein kinase C-alpha; c-myb. The experience gained from these early clinical trials will be applicable to the next generation of antisense agents in development. These may include molecules with novel backbones or other structural

  20. Oncolytic virotherapy for human malignant mesothelioma: recent advances.

    PubMed

    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.

  1. 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

  2. Advanced Cytologic Techniques for the Detection of Malignant Pancreatobiliary Strictures

    PubMed Central

    Moreno Luna, Laura E.; Kipp, Benjamin; Halling, Kevin C.; Sebo, Thomas J.; Kremers., Walter K.; Roberts, Lewis R.; Barr Fritcher, Emily G.; Levy, Michael J.; Gores, Gregory J.

    2006-01-01

    Background & Aims Two advanced cytologic techniques for detecting aneuploidy, digital image analysis (DIA) and fluorescence in situ hybridization (FISH) have recently been developed to help identify malignant pancreatobiliary strictures. The aim of this study was to assess the clinical utility of cytology, DIA, and FISH for the identification of malignant pancreatobiliary strictures. Methods Brush cytologic specimens from 233 consecutive patients undergoing ERCP for pancreatobiliary strictures were examined by all three techniques. Strictures were stratified as proximal (n=33) or distal (n=114) based on whether they occurred above or below the cystic duct, respectively. Strictures in patients with PSC (n=86) were analyzed separately. Results Despite the stratification, the performances of the tests were similar. Routine cytology has a low sensitivity (5–20%) but 100% specificity. Because of the high specificity for cytology, we assessed the performance of the other tests when routine cytology was negative. In this clinical context, FISH had an increased sensitivity (35–60%) when assessing for chromosomal gains (polysomy) while preserving the specificity of cytology. The sensitivity and specificity of DIA was intermediate as compared to routine cytology and FISH, but was additive to FISH values demonstrating only trisomy of chromosome 7 or chromosome 3. Conclusions These findings suggest that FISH and DIA increase the sensitivity for the diagnosis of malignant pancreatobiliary tract strictures over that obtained by conventional cytology while maintaining an acceptable specificity. PMID:17030177

  3. Recent advances in T-cell immunotherapy for haematological malignancies.

    PubMed

    Rouce, Rayne H; Sharma, Sandhya; Huynh, Mai; Heslop, Helen E

    2017-03-01

    In vitro discoveries have paved the way for bench-to-bedside translation in adoptive T cell immunotherapy, resulting in remarkable clinical responses in a variety of haematological malignancies. Adoptively transferred T cells genetically modified to express CD19 CARs have shown great promise, although many unanswered questions regarding how to optimize T-cell therapies for both safety and efficacy remain. Similarly, T cells that recognize viral or tumour antigens though their native receptors have produced encouraging clinical responses. Honing manufacturing processes will increase the availability of T-cell products, while combining T-cell therapies has the ability to increase complete response rates. Lastly, innovative mechanisms to control these therapies may improve safety profiles while genome editing offers the prospect of modulating T-cell function. This review will focus on recent advances in T-cell immunotherapy, highlighting both clinical and pre-clinical advances, as well as exploring what the future holds.

  4. 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

  5. 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

  6. Malignancies in autoimmune rheumatic diseases - a mini-review.

    PubMed

    Szekanecz, Zoltán; Szekanecz, Eva; Bakó, Gyula; Shoenfeld, Yehuda

    2011-01-01

    Paraneoplastic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases, are the result of a wide variety of tumor-derived biologic mediators like hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Systemic inflammatory rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma or dermatomyositis, may increase the risk for the development of malignancies, predominantly lymphoproliferative disorders. Immunosuppressive drugs and biological agents may also be carcinogenic. However, sustained inflammatory activity seems to be the primary risk factor for malignancies in autoimmune diseases. Tumor-associated antigens may be produced by inflammatory cells and their production may be increased in rheumatoid arthritis and other autoimmune diseases.

  7. Association Between Coeliac Disease and Risk of Any Malignancy and Gastrointestinal Malignancy

    PubMed Central

    Han, Yuehua; Chen, Wuzhen; Li, Peiwei; Ye, Jun

    2015-01-01

    Abstract Coeliac disease (CD) is reported to be associated with risk of malignancy; however, this association remains unclear. We aimed to systematically evaluate the association between CD and risk of all malignancies as well as gastrointestinal (GI) malignancy specifically. The PUBMED and EMBASE databases were searched to identify eligible studies from 1960 to March 2015, without restriction. Two reviewers independently performed the study inclusion and data extraction methods. Odds ratios (ORs), risk ratios, or standardized incidence ratios were pooled using either a fixed- or a random-effects model. Sensitivity and subgroup analyses were used to explore sources of heterogeneity. A total of 17 studies were included in this meta-analysis. The pooled OR for risk of all malignancies was 1.25 (95% confidence interval [CI] 1.09–1.44), whereas the pooled OR for risk of GI malignancy was 1.60 (95% CI 1.39–1.84) and suggested an inverse association with CD. Moreover, patients with CD were at a higher risk of esophageal cancer (pooled OR = 3.72, 95% CI 1.90–7.28) and small intestinal carcinoma (pooled OR = 14.41, 95% CI 5.53–37.60), whereas no significant associations were observed for other GI cancers, including gastric, colorectal, liver, and pancreatic cancers. Subgroup analyses also indicated that the results were influenced by the CD diagnostic method, as well as the follow-up time after CD diagnosis. CD was associated with increased risk of all malignancies as well as GI malignancies, including esophageal cancer and small intestinal carcinoma. PMID:26402826

  8. 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

  9. 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

  10. 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

  11. 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.

  12. What we learned from difficult hepatectomies in patients with advanced hepatic malignancy

    PubMed Central

    Jung, Bo Hyun; Lee, Jae Hoon; Lee, Sang Yeup; Song, Dae Keun; Hwang, Ji Woong; Hwang, Dae Wook; Lee, Young-Joo

    2011-01-01

    Backgrounds/Aims By reviewing difficult resections for advanced hepatic malignancies, we discuss the effectiveness and extended indications for hepatectomy in such patients. Methods We reviewed 7 patients who underwent extensive surgery between July 2008 and March 2011 for advanced hepatic malignancies. They had stage IV disease, except for in one case that was a stage IIIC (T4N0M0) hepatocellular carcinoma (HCC). Results Patient 1 with intrahepatic cholangiocarcinoma (IHCC) underwent right hemihepatectomy and resection of the bile duct and left portal vein. At 39 months after surgery, she had no recurrence or metastasis. Patient 2 with HCC underwent palliative right trisectionectomy. At 38 months after surgery, he is alive despite residual pulmonary metastases. Patient 3 with HCC invading the hepatic vein and diaphragm underwent right trisectionectomy and caval venoplasty. At 12 months after surgery, he had no recurrence or metastasis. Patient 4, who had 2 large HCCs and pulmonary thromboembolism, underwent a right trisectionectomy. At 7 months after surgery, he had no evidence of recurred HCC. Patient 5, who had IHCC invading her inferior vena cava and main portal vein, underwent preoperative radiotherapy, left hemihepatectomy, and caval resection. At 20 months after surgery, she is well despite a caval thrombus. Patient 6 and 7 underwent repeated surgery due to a recurred IHCC and metastatic colon cancer, respectively. In addition, they are alive during each 20 and 17 months after surgery. Conclusions Despite macroscopic extrahepatic metastases or major vessel involvement, extensive surgery for advanced hepatic malignancy may result in relatively favorable outcomes and be important modality for improving of survival in such patients. PMID:26421042

  13. Advanced MRI applications and findings of malignant phyllodes tumour: review of two cases.

    PubMed

    Alhabshi, Sharifah Majedah Idrus; Rahmat, Kartini; Abu Hassan, Hasyma; Westerhout, Caroline Judy; Chandran, Patricia Ann

    2013-05-01

    Phyllodes tumour or cystosarcoma phyllodes is a rare stromal breast tumour that is usually benign but on rare occasions can turn malignant. Non-specificity of the imaging features on sonography and mammography makes it difficult to distinguish malignant from benign counterparts solely based on imaging. The final diagnosis is still highly dependent on histopathological assessment. Herein, we describe two cases of malignant phyllodes tumour with emphasis on magnetic resonance (MR) imaging features using advanced MR applications.

  14. Helicobacter pylori and non-malignant diseases.

    PubMed

    Furuta, Takahisa; Delchier, Jean-Charles

    2009-09-01

    It is well known that Helicobacter pylori infection is associated with many nonmalignant disorders such as gastritis, peptic ulcer, gastroesophageal reflux disease (GERD), gastric polyp, nonsteroidal anti-inflammatory drug (NSAID)/aspirin-induced gastric injury, and functional dyspepsia. In 2008, interesting articles on the association of H. pylori infection with these disorders were presented, some of which intended to reveal the mechanisms of inter-individual differences in response to H. pylori infection, and have demonstrated that genetic differences in host and bacterial factors as well as environmental factors account for these differences. A decline in the occurrence of peptic ulcer related to H. pylori was confirmed. An inverse relationship between H. pylori infection and GERD was also confirmed but the impact of gastric atrophy on the prevention of GERD remained debatable. For NSAID-induced gastric injury, eradication of H. pylori infection has been recommended. During this year, eradication of H. pylori infection was recommended for patients treated with antiplatelet therapy as well as aspirin and NSAID. It was also reported that for patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit.

  15. Infectious and Inflammatory Diseases Masquerading as Head and Neck Malignancy.

    PubMed

    Greene; Sandin; Hiemenz; Toney

    1994-01-01

    Lesions of the head and neck and upper respiratory tract can be quite difficult to diagnose at times when presenting symptoms and signs appear out of character or biopsy of affected tissue reveals nonspecific results. A heightened awareness of important historical facts such as place of birth and residence, travel and occupation may provide important clues to narrow the differential diagnosis. Not all destructive ulcers and tumors of the head and neck are malignant. Inflammatory and infectious diseases that mimic cancer are presented.

  16. 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

  17. Advances in the systemic therapy of malignant pleural mesothelioma.

    PubMed

    Fennell, Dean A; Gaudino, Giovanni; O'Byrne, Kenneth J; Mutti, Luciano; van Meerbeeck, Jan

    2008-03-01

    Malignant pleural mesothelioma is an aggressive thoracic malignancy associated with exposure to asbestos, and its incidence is anticipated to increase during the first half of this century. Chemotherapy is the mainstay of treatment, yet sufficiently robust evidence to substantiate the current standard of care has emerged only in the past 5 years. This Review summarizes the evidence supporting the clinical activity of chemotherapy, discusses the use of end points for its assessment and examines the influence of clinical and biochemical prognostic factors on the natural history of malignant pleural mesothelioma. Early-phase clinical trials of second-line and novel agents are emerging from an increased understanding of mesothelioma cell biology. Coupled with high-quality translational research, such developments have real potential to improve the outlook of patients at a time of increasing incidence.

  18. Imaging of the thyroid in benign and malignant disease.

    PubMed

    Intenzo, Charles M; Dam, Hung Q; Manzone, Timothy A; Kim, Sung M

    2012-01-01

    The thyroid gland was one of the first organs imaged in nuclear medicine, beginning in the 1940s. Thyroid scintigraphy is based on a specific phase or prelude to thyroid hormone synthesis, namely trapping of iodide or iodide analogues (ie, Tc99m pertechnetate), and in the case of radioactive iodine, eventual incorporation into thyroid hormone synthesis within the thyroid follicle. Moreover, thyroid scintigraphy is a reflection of the functional state of the gland, as well as the physiological state of any structure (ie, nodule) within the gland. Scintigraphy, therefore, provides information that anatomical imaging (ie, ultrasound, computed tomography [CT], magnetic resonance imaging) lacks. Thyroid scintigraphy plays an essential role in the management of patients with benign or malignant thyroid disease. In the former, the structure or architecture of the gland is best demonstrated by anatomical or cross-sectional imaging, such as ultrasound, CT, or even magnetic resonance imaging. The role of scintigraphy, however, is to display the functional state of the thyroid gland or that of a clinically palpable nodule within the gland. Such information is most useful in (1) patients with thyrotoxicosis, and (2) those patients whose thyroid nodules would not require tissue sampling if their nodules are hyperfunctioning. In neoplastic thyroid disease, thyroid scintigraphy is often standard of care for postthyroidectomy remnant evaluation and in subsequent thyroid cancer surveillance. Planar radioiodine imaging, in the form of the whole-body scan (WBS) and posttherapy scan (PTS), is a fundamental tool in differentiated thyroid cancer management. Continued controversy remains over the utility of WBS in a variety of patient risk groups and clinical scenarios. Proponents on both sides of the arguments compare WBS with PTS, thyroglobulin, and other imaging modalities with differing results. The paucity of large, randomized, prospective studies results in dependence on consensus

  19. [Ectopic pancreas mimicking advanced gastric malignancy--case report].

    PubMed

    Zawada, Iwona; Lewosiuk, Agnieszka; Hnatyszyn, Krzysztof; Patalan, Michał; Woyke, Stanisław; Kostyrka, Roman; Marlicz, Krzysztof; Starzyńska, Teresa

    2012-04-01

    Ectopic pancreas is the most common type of ectopic tissue in gastrointestinal tract. It is typically asymptomatic, presenting as a small submucosal lesion in prepyloric region of stomach. The diagnosis is usually incidental, during gastroscopy. The patient with symptomatic heterotropic pancreas, mimicking gastric malignancy was described.

  20. Malignant tumors of the larynx: Clinicopathologic profile and implication for late disease presentation

    PubMed Central

    Fasunla, Ayotunde James; Ogundoyin, Oluwole Agboola; Onakoya, Paul Adekunle; Nwaorgu, Onyekwere George

    2016-01-01

    Background: Malignant laryngeal tumors are uncommon. Late presentation of the disease may worsen management outcomes. We described the epidemiologic, clinicopathologic profile, and management outcomes of laryngeal tumors in a tertiary health institution in Nigeria. Materials and Methods: An 11-year retrospective review of medical records of patients managed for malignant laryngeal tumor at the University College Hospital, Ibadan, Nigeria, was performed. Results: There were 97 patients comprising 74 (76.3%) males and 23 (23.7%) females with a mean age of 60.48 ± 12.15 years. The mean duration of illness was 7.3 ± 3.8 months. History of cigarette smoking and alcohol consumption was in 2.1% and 14.4% patients, respectively. The most common clinical presentations were hoarseness, cough, and dyspnea. Transglottis (91.8%) was the most common anatomic tumor location and 92.8% patients presented in advanced disease stage. Four histologic types were identified with squamous cell carcinoma accounting for 96.9%. About 92% patients had emergency tracheostomy and 56 (57.7%) patients had total laryngectomy. The postoperative complications were pharyngocutaneous fistula (5.2%) and peristomal recurrence (3.1%). The 5-year survival rate was 52.5%. Conclusions: Malignant laryngeal tumors are uncommon, but more females are getting the disease. Squamous cell carcinoma is the most common histologic variant. Late stage disease presentation and initial wrong diagnosis contributed to the poor management outcome. PMID:27833247

  1. Role of laparoscopy in the staging of malignant disease.

    PubMed

    Pratt, B L; Greene, F L

    2000-08-01

    Although diagnostic laparoscopy has been used by surgeons and gastroenterologists since the early 1900s, today's surgical oncologists have been relatively slow to embrace this technology. Together with the fervor and benefits afforded by laparoscopic therapeutic interventions in the management of patients with benign disease and the diagnostic usefulness in blunt trauma and abdominal pain, awareness has been rekindled regarding the advantages of laparoscopy for the staging of abdominal malignancy. As surgeons begin to realize that extirpative procedures are doomed to failure in curing patients with diffuse abdominal metastases disclosed on laparoscopic assessment, palliative measures, such as stent placement, ablative procedures, balloon dilatation, intraluminal high-dose radiation, and laser techniques will be used commonly by surgical endoscopists and gastroenterologists. Similarly, it is hoped that the use of systemic chemotherapy will achieve better specificity in cell destruction in patients identified laparoscopically to have uncontained disease in the abdominal cavity. The sensitivity of sonography combined with laparoscopy has been shown to approach that of celiotomy in the evaluation of solid organs, thereby avoiding unnecessary laparotomy and its associated morbidities. Using sonography as a complement to laparoscopy will extend the usefulness of both techniques. The application of laparoscopy and the advent of miniaturized laparoscopic instrumentation (Fig. 7), both diagnostic and therapeutic, in the management of patients with abdominal malignancy will be limited only by the creativity and expertise of physicians and instrument makers.

  2. Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

    PubMed

    Yuji, Koichiro; Miyakoshi, Shigesaburo; Kato, Daisuke; Miura, Yuji; Myojo, Tomohiro; Murashige, Naoko; Kishi, Yukiko; Kobayashi, Kazuhiro; Kusumi, Eiji; Narimatsu, Hiroto; Hamaki, Tamae; Matsumura, Tomoko; Kami, Masahiro; Fukuda, Takahiro; Masuo, Shigeru; Masuoka, Kazuhiro; Wake, Atsushi; Ueyama, Junichi; Yoneyama, Akiko; Miyamoto, Ko; Nagoshi, Haruhisa; Matsuzaki, Michio; Morinaga, Shinichi; Muto, Yoshitomo; Takeue, Yoichi; Taniguchi, Shuichi

    2005-04-01

    We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.

  3. Cancer Genome Sequencing: Understanding Malignancy as a Disease of the Genome, its Conformation, and its Evolution

    PubMed Central

    Patel, Lalit R.; Nykter, Matti; Chen, Kexin; Zhang, Wei

    2013-01-01

    Advances in cancer genomics have been propelled by the steady evolution of molecular profiling technologies. Over the past decade, high-throughput sequencing technologies have matured to the point necessary to support disease-specific shotgun sequencing. This has compelled whole-genome sequencing studies across a broad panel of malignancies. The emergence of high-throughput sequencing technologies has inspired new chemical and computational techniques enabling interrogation of cancer-specific genomic and transcriptomic variants, previously unannotated genes, and chromatin structure. Finally, recent progress in single-cell sequencing holds great promise for studies interrogating the consequences of tumor evolution in cancers presenting with genomic heterogeneity. PMID:23111104

  4. 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.

  5. Intra-Abdominal Actinomycosis Mimicking Malignant Abdominal Disease

    PubMed Central

    Oguejiofor, Njideka; Al-Abayechi, Sarah; Njoku, Emmanuel

    2017-01-01

    Abdominal actinomycosis is a rare infectious disease, caused by gram positive anaerobic bacteria, that may appear as an abdominal mass and/or abscess (Wagenlehner et al. 2003). This paper presents an unusual case of a hemodynamically stable 80-year-old man who presented to the emergency department with 4 weeks of worsening abdominal pain and swelling. He also complains of a 20-bound weight loss in 2 months. A large tender palpable mass in the right upper quadrant was noted on physical exam. Laboratory studies showed a normal white blood cell count, slightly decreased hemoglobin and hematocrit, and mildly elevated total bilirubin and alkaline phosphatase. A CT with contrast was done and showed a liver mass. Radiology and general surgery suspected malignancy and recommended CT guided biopsy. The sample revealed abundant neutrophils and gram positive rods. Cytology was negative for malignancy and cultures eventually grew actinomyces. High dose IV penicillin therapy was given for 4 weeks and with appropriate response transitioned to oral antibiotic for 9 months with complete resolution of symptoms. PMID:28299215

  6. Oral mucocutaneous diseases: clinicopathologic analysis and malignant transformation.

    PubMed

    Jaafari-Ashkavandi, Zohreh; Mardani, Maryam; Pardis, Soheil; Amanpour, Sara

    2011-05-01

    Oral mucocutaneous diseases (MCDs) are a heterogeneous group of disorders that could involve oral mucous membrane frequently. The purpose of this study was analysis of clinicopathologic features and relative frequency of MCDs with emphasize on malignant transformation of oral lichen planus (OLP). In this retrospective study, clinical data regarding to site of involvement, patient's age and sex, and accompanied symptoms were noted, and pathologic slides of OLP were reviewed for the detection of dysplastic changes. Among 309 patients, OLP and pemphigus vulgaris were the first and second most common MCDs. Buccal mucosa was the most frequent affected site. Female predominance (70.23%) and mean age of 45.3 years were seen. Approximately 12.4% of OLPs showed dysplastic and neoplastic changes. In conclusion, MCD with oral manifestation is most probably to be OLP and pemphigus vulgaris rather than other rare disorders. Malignant transformation may occur in all forms of OLP, and hence, regular, exact follow-up of the patient is necessary for enhancing quality of life.

  7. 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.

  8. Management of growth failure in the treatment of malignant disease

    SciTech Connect

    Leiper, A.D. )

    1990-01-01

    Growth failure due to endocrine dysfunction as a result of treatment for malignant disease is becoming increasingly common. It may occur after cranial or craniospinal irradiation given in the treatment of acute lymphoblastic leukemia and brain tumors, and is often coupled with early or precocious puberty. It also occurs after neck and gonadal radiation and is particularly severe after total body irradiation where multiple endocrine deficiencies frequently occur. Failure to appreciate its occurrence or failure to institute therapy early enough may lead to short stature in adult life. Accurate and regular monitoring of standing and sitting height, bone age, and endocrine data should be undertaken by the oncologist in close collaboration with an endocrinologist, to ensure appropriate management of the patient. 17 references.

  9. 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.

  10. Second malignancies after Hodgkin's disease: the Munich experience.

    PubMed

    Munker, R; Grützner, S; Hiller, E; Aydemir, U; Enne, W; Dietzfelbinger, H; Busch, M; Haas, R; Emmerich, B; Schmidt, M; Dühmke, E; Hölzel, D; Wilmanns, W

    1999-12-01

    The occurrence of second malignancies (SM) is an important late event following the treatment of Hodgkin's disease (HD). We sought to determine the incidence, the risk factors, and the prognosis of SM in our population of patients with HD. A total of 1120 patients diagnosed with HD were registered at six participating institutions in Munich (calendar period 1974-1994). The mean follow-up for the development of SM was 9.1 years. A cumulative treatment score was calculated for both radio- and chemotherapy. The relative and absolute risks of SM were established. All SM were investigated for response to treatment and outcome. We observed 85 SM [eight leukemias, 22 non-Hodgkin's lymphomas (NHL), two plasma cell neoplasias, and 53 solid tumors]. Five patients developed third malignancies. The relative risk of developing a second neoplasm was compared with that within the normal population and was 3.1-fold. The risk varied according to the category of SM. Higher relative risks (20.5 and 25.9-fold), but lower absolute risks were observed for leukemias and non-Hodgkin's lymphomas. Solid tumors had lower relative risks (1.8-fold). Splenectomy increased the risk of SM (relative risk 4.4-fold versus 2.7-fold). The risk of SM did not correlate with the initial treatment (radio- or chemotherapy) and did not decrease with prolonged follow-up. The cumulative intensity of radiotherapy, chemotherapy, or the two modalities combined correlated with the risk of SM. Since some cases occurred early after diagnosis, not all second neoplasms can be considered treatment-associated. After 15 years, an actuarial risk of 11.7% was calculated for all SM, of 1.0% for leukemias, of 3.0% for NHL, and of 7.7% for solid tumors. The prognosis of SM varied between good (thyroid cancer, melanoma: median survival 5+ years), average (breast cancer, NHL), and poor (acute myeloid leukemias, lung cancers: median survival 9 months). With the exception of NHL, second cancers often occurred in topographic

  11. Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma.

    PubMed

    Huse, Jason T; Holland, Eric C

    2010-05-01

    Malignant brain tumours continue to be the cause of a disproportionate level of morbidity and mortality across a wide range of individuals. The most common variants in the adult and paediatric populations - malignant glioma and medulloblastoma, respectively - have been the subject of increasingly intensive research over the past two decades that has led to considerable advances in the understanding of their basic biology and pathogenesis. This Review summarizes these developments in the context of the evolving notion of molecular pathology and discusses the implications that this work has on the design of new treatment regimens.

  12. Recent advances in heartworm disease.

    PubMed

    Guerrero, J; McCall, J W; Genchi, C; Bazzocchi, C; Kramer, L; Simòn, F; Martarino, M

    2004-10-28

    This compilation of articles consists of four papers presented at the 19th International Conference of the World Association for the Advancement of Veterinary Parasitology (WAAVP) (held in New Orleans, LA, USA, on 10–14 August 2003) in a symposium session titled “ Recent Advances in Heartworm Disease,” organized and chaired by JohnW. McCall and Jorge Guerrero. The first paper(Guerrero) covered the American Heartworm Society’s most recent revision of their guidelines for the diagnosis, prevention, and management of heartworm infection in dogs, based on new research and clinical experience, particularly in the areas of heartworm chemoprophylaxis, adulticide therapy,and serologic testing and retesting. The entire updated 2003 “Guidelines” are presented herein.One paper (McCall) reviewed the “soft-kill” adulticidal and “safety-net” (reach-back, retroactive,clinical prophylactic) activity of prolonged dosing of prophylactic doses of macrocyclic lactones,concluding that ivermectin is the most effective in this way, milbemycin oxime is the least effective,and the activity of injectable moxidectin and selamectin lies between that of ivermectin and milbemycin oxime. The two remaining papers provided an overview of the discovery, rediscovery,phylogeny, and biological association between Wolbachia endosymbionts and filarial nematodes(Genchi and co-authors) and compelling evidence that Wolbachia may play a major role in the immunopathogenesis of filarial diseases of man and animals (Kramer and co-authors).

  13. The appendix: a spectrum of benign and malignant disease.

    PubMed

    Lord, Christopher; Broadhurst, Jack; Sleight, Simon; McGee, Shaun; Wills, Mark

    2017-02-02

    This article discusses the radiological appearances and subsequent management of a diverse spectrum of benign and malignant appendiceal pathologies, including those masquerading as acute appendicitis.

  14. Advances in Alcoholic Liver Disease

    PubMed Central

    Beier, Juliane I.; Arteel, Gavin E.

    2013-01-01

    Alcoholic liver disease (ALD) remains a leading cause of death from liver disease in the United States. In studies from the Veterans Administration, patients with cirrhosis and superimposed alcoholic hepatitis had greater than 60% mortality over a 4-year period, with most of those deaths occurring in the first month. Thus, the prognosis for this disease is more ominous than for many common types of cancer (eg, breast, prostate, and colon). Moreover, ALD imposes a significant economic burden from lost wages, health care costs, and lost productivity. Unfortunately, there is still no Food and Drug Administration–approved or widely accepted drug therapy for any stage of ALD. Thus, a pressing need exists for a more detailed understanding of mechanisms of liver injury. This article reviews recent advances in mechanisms and therapy related to five major areas of direct relevance to ALD: oxidative stress; gut-liver axis and cytokine signaling; malnutrition; fibrin/clotting; and stellate cell activation/fibrosis. We also review why therapies related to these mechanisms have performed well in experimental animals and in vitro systems, but have not necessarily translated into effective therapy for humans with ALD. PMID:21088999

  15. Improvement of Liver Function, Quality of Life and Survival after Insertion of Endoprosthesis in Advance Malignant Biliary Obstruction.

    PubMed

    Ullah, A A; Rahman, A; Chowdhury, L H; Bhuiya, A H

    2017-01-01

    Obstructive jaundice due to advance malignancy is a fatal problem. It most commonly occurs at the distal common bile duct or at the hilum of liver. Magnetic Resonance Cholangio Pancreatography (MRCP) and Computed Tomography (CT) are most useful in identifying the underlying cause as well as localize the position of the stricture. For those patients with unresectable disease, progressive jaundice constitutes an immediate threat to their survival, in addition to significant loss to their quality of life secondary to pruritus, malaise and cholangitis. Effective and lasting decompression of the biliary tree is a priority and consists of positioning of a biliary endoprosthesis (stent). To observe the improvement of liver function, quality of life and survival after successful insertion of endoprosthesis (stenting) in malignant biliary obstruction, a study was performed in the department of surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from September 2013 to August 2014, in 50 patients with clinically visible jaundice and unresectable disease. There were significant (p<0.001) reductions in the levels of serum bilirubin, serum alkaline phosphatase, serum SGPT and Prothrombin time from the time of admission to 2 weeks and 3 weeks after stenting. Physical and functional quality of life was greatly improved 2-4 weeks after stenting, where emotional quality remained the same throughout the study period. Successful palliation by stenting of malignant biliary obstruction is a priority to achieve improvements in liver function, quality of life and prolong survival. Endoscopic stent placement appears to be safe, well tolerated and can be offered without delay as a primary treatment option for all patients with unresectable malignant biliary lesion.

  16. Mitochondrial diseases: advances and issues

    PubMed Central

    Scarpelli, Mauro; Todeschini, Alice; Volonghi, Irene; Padovani, Alessandro; Filosto, Massimiliano

    2017-01-01

    Mitochondrial diseases (MDs) are a clinically heterogeneous group of disorders caused by a dysfunction of the mitochondrial respiratory chain. They can be related to mutation of genes encoded using either nuclear DNA or mitochondrial DNA. The advent of next generation sequencing and whole exome sequencing in studying the molecular bases of MDs will bring about a revolution in the field of mitochondrial medicine, also opening the possibility of better defining pathogenic mechanisms and developing novel therapeutic approaches for these devastating disorders. The canonical rules of mitochondrial medicine remain milestones, but novel issues have been raised following the use of advanced diagnostic technologies. Rigorous validation of the novel mutations detected using deep sequencing in patients with suspected MD, and a clear definition of the natural history, outcome measures, and biomarkers that could be usefully adopted in clinical trials, are mandatory goals for the scientific community. Today, therapy is often inadequate and mostly palliative. However, important advances have been made in treating some clinical entities, eg, mitochondrial neuro-gastrointestinal encephalomyopathy, for which approaches using allogeneic hematopoietic stem cell transplantation, orthotopic liver transplantation, and carrier erythrocyte entrapped thymidine phosphorylase enzyme therapy have recently been developed. Promising new treatment methods are being identified so that researchers, clinicians, and patients can join forces to change the history of these untreatable disorders. PMID:28243136

  17. Recent Advances in Celiac Disease.

    PubMed

    Murch, Simon

    2016-11-01

    Recent diagnostic advances have demonstrated that celiac disease is relatively common although most patients have less florid symptoms than previously recognised. The mucosal lesion of this autoimmune disorder depends on both adaptive and innate immune responses. The characteristic antibodies to tissue transglutaminase-2 (tTG-2) and deamidated gliadin peptides may be produced in persons possessing the relevant HLA-DQ genotypes if intact gliadin peptides can penetrate the epithelial barrier to reach antigen presenting cells. Progression from celiac autoimmunity to overt disease may depend on innate immune mechanisms, not HLA-restricted, where IL-15 is generated within the epithelial compartment. A specific innate immune response previously thought restricted to invertebrates, the encapsulation reaction, may contribute to mucosal volume expansion through recruitment of syndecan-expressing leukocytes and stimulated matrix production. It is notable that tissue transglutaminase is critical in this reaction in insects, and that the very few insects that can predate wheat, possess specific salivary or intestinal enzymes that degrade gluten. Animal models in HLA-DQ transgenic mice suggest that the microbial flora of the intestine may play a role in host responses and modulate the evolution of the disease. This suggests that therapeutic modulation of the microbiome may contribute to management of celiac disease. In developing world countries, there is a potential difficulty in histological diagnosis because of the widespread incidence of environmental enteropathy amongst apparently healthy children. Thus, recognition of local patterns of enteropathy will be important for histopathologists, and high titre tTG-2 autoantibody titres may hold considerable diagnostic significance.

  18. Advances in motor neurone disease.

    PubMed

    Bäumer, Dirk; Talbot, Kevin; Turner, Martin R

    2014-01-01

    Motor neurone disease (MND), the commonest clinical presentation of which is amyotrophic lateral sclerosis (ALS), is regarded as the most devastating of adult-onset neurodegenerative disorders. The last decade has seen major improvements in patient care, but also rapid scientific advances, so that rational therapies based on key pathogenic mechanisms now seem plausible. ALS is strikingly heterogeneous in both its presentation, with an average one-year delay from first symptoms to diagnosis, and subsequent rate of clinical progression. Although half of patients succumb within 3-4 years of symptom onset, typically through respiratory failure, a significant minority survives into a second decade. Although an apparently sporadic disorder for most patients, without clear environmental triggers, recent genetic studies have identified disease-causing mutations in genes in several seemingly disparate functional pathways, so that motor neuron degeneration may need to be understood as a common final pathway with a number of upstream causes. This apparent aetiological and clinical heterogeneity suggests that therapeutic studies should include detailed biomarker profiling, and consider genetic as well as clinical stratification. The most common mutation, accounting for 10% of all Western hemisphere ALS, is a hexanucleotide repeat expansion in C9orf72. This and several other genes implicate altered RNA processing and protein degradation pathways in the core of ALS pathogenesis. A major gap remains in understanding how such fundamental processes appear to function without obvious deficit in the decades prior to symptom emergence, and the study of pre-symptomatic gene carriers is an important new initiative.

  19. Second Malignant Neoplasms and Cardiovascular Disease Following Radiotherapy

    PubMed Central

    Ng, Andrea K.; Allan, James M.; Pui, Ching-Hon; Kennedy, Ann R.; Xu, X. George; Purdy, James A.; Applegate, Kimberly; Yahalom, Joachim; Constine, Louis S.; Gilbert, Ethel S.; Boice, John D.

    2012-01-01

    Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose–response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose–response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies. PMID:22312134

  20. 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.

  1. Positron Emission Tomography (PET) for benign and malignant disease

    PubMed Central

    Visioni, Anthony; Kim, Julian

    2011-01-01

    Synopsis Functional imaging using radiolabeled probes which specifically bind and accumulate in target tissues has improved the sensitivity and specificity of conventional imaging. Positron Emission Tomography using modified glucose probes (FDG-PET) has demonstrated improved diagnostic accuracy in differentiating benign from malignant lesions in the setting of solitary pulmonary nodules. In addition, FDG-PET has become a useful modality in pre-operative staging of patients with lung cancer and is being tested with many other malignancies for its ability to change patient management. This article provides an overview of the current status of FDG-PET and presents the challenges of moving towards routine use. PMID:21184913

  2. Bilateral dissemination of malignant pleural mesothelioma via iatrogenic buffalo chest: a rare route of disease progression.

    PubMed

    Ikezoe, Kohei; Tanaka, Eisaku; Tanizawa, Kiminobu; Hashimoto, Seishu; Shindo, Toru; Noma, Satoshi; Kobashi, Yoichiro; Taguchi, Yoshio

    2012-09-01

    Buffalo chest refers to the pleuro-pleural communication that results in a single pleural cavity. Iatrogenic buffalo chest can occur following heart or heart-lung transplantation and other major thoracic surgeries. We present the case of malignant pleural mesothelioma in which iatrogenic buffalo chest after extended thymectomy caused bilateral pneumothoraces and contralateral dissemination of the disease. The free communication between bilateral pleural cavities had facilitated the rapid progression of tumor and the consequent bilateral malignant pleural effusions had made the management of disease much more difficult, leading to the early fatal outcome. To our knowledge, this is the first case of buffalo chest that was associated with bilateral malignant pleural effusions.

  3. 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

  4. 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

  5. Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases.

    PubMed

    Tucunduva, Luciana; Volt, Fernanda; Cunha, Renato; Locatelli, Franco; Zecca, Marco; Yesilipek, Akif; Caniglia, Maurizio; Güngör, Tayfun; Aksoylar, Serap; Fagioli, Franca; Bertrand, Yves; Addari, Maria Carmen; de la Fuente, Josu; Winiarski, Jacek; Biondi, Andrea; Sengeloev, Henrik; Badell, Isabel; Mellgren, Karin; de Heredia, Cristina Díaz; Sedlacek, Petr; Vora, Ajay; Rocha, Vanderson; Ruggeri, Annalisa; Gluckman, Eliane

    2015-04-01

    Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD.

  6. 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.

  7. Radiographic Differentiation of Advanced Fibrocystic Lung Diseases.

    PubMed

    Akira, Masanori

    2017-03-01

    The concept of end-stage lung disease suggests a final common pathway for most diffuse parenchymal lung diseases. In accordance with this concept, end-stage disease is characterized radiographically and pathologically by the presence of extensive honeycombing. However, sequential computed tomographic (CT) scans obtained from patients with chronic diffuse lung disease evolve over time to show various advanced lung disease patterns other than honeycombing. In addition, several radiographically distinct honeycomb patterns, including microcystic, macrocystic, mixed, and combined emphysema and honeycombing, differentiate one advanced lung disease from another. For example, usual interstitial pneumonia (IP) usually shows mixed microcystic and macrocystic honeycombing. In contrast, CT images of long-standing fibrotic nonspecific IP typically show only small, scattered foci of honeycombing; instead, most enlarged airspaces observed in the advanced stage of this disease represent dilatation of bronchioles. In desquamative IP and pulmonary Langerhans cell histiocytosis, focal opacities typically evolve into emphysema-like lesions seen on CT imaging. In combined pulmonary fibrosis and emphysema and sarcoidosis, the cysts tend to be larger than those observed in usual IP. Sequential CT scans in other chronic, diffuse lung diseases also show various distinctive changes. This article highlights radiographic patterns of lung destruction that belie a single common pathway to end-stage lung disease. Recognition of distinct radiographic patterns of lung destruction can help differentiate diffuse parenchymal lung diseases, even in advanced stages of disease evolution.

  8. 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

  9. Asbestos-related pleuropulmonary diseases: benign and malignant.

    PubMed

    Lazarus, Angeline; Massoumi, Ali; Hostler, Jordanna; Hostler, David C

    2012-05-01

    Asbestos is known for its desirable properties of thermal and heat resistance along with excellent strength and durability. It was widely used in many industries since the late 19th century, until its adverse effects on health were recognized. The occurrence of pleuropulmonary changes from exposure to asbestos often has a latency period of 20 to 30 years. The use of asbestos has been banned, regulated, and minimized in many countries, but in several developing countries, the use of asbestos in industries is still a common practice. In this article, the benign and malignant clinical manifestations of asbestos exposure are discussed.

  10. 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.

  11. The Pathophysiologic Basis of Anaemia in Patients with Malignant Diseases.

    PubMed

    Ibrahim, Umma A; Yusuf, Aminu A; Ahmed, Sagir G

    2016-09-01

    Cancer patients frequently present with anaemia that may result from the direct or indirect effects of the tumor or its treatment. Anaemia is an independent adverse prognostic factor that exerts negative influence on quality of life and survival of cancer patients. Anaemia in malignant disorders often arises from an interplay of multiple aetiological and pathophysiologic mechanisms. Understanding these mechanisms will help the oncologist identify and treat specific causes of the anaemia thereby minimizing the use of blood transfusion, which is associated with many adverse effects. This paper reviewed the various aetiological and pathophysiologic mechanisms of anaemia in cancer patients including direct and indirect tumour effects that lead to reduced red cell production or increased red cell destruction via a myriad of mechanisms ranging from marrow infiltration and cancer-associated acute myelonecrosis to chronic inflammation, blood loss, iron, folate, vitamin B12 and other nutrients deficiencies, malignancy related renal injury, pure red cell aplasia, hypersplenism, haemophagocytic syndrome, red cell autoantibody production, non-immune red cell fragmentation and cytotoxic therapy-induced erythroid cell apoptosis and eryptosis. Hence anaemia in cancer patients is attributable to a wide spectrum of aetiological factors with multiple and sometimes overlapping pathophysiologic mechanisms. It is therefore necessary for the oncologists to thoroughly investigate all cases of anaemia with the aim of identifying the actual causative factors in order to offer more sustainable cause-specific treatment modalities that will minimize the use of blood transfusion with its attendant adverse effects.

  12. Evaluation of intrathecal drug delivery system for intractable pain in advanced malignancies

    PubMed Central

    Zheng, Shuyue; He, Liangliang; Yang, Xiaohui; Li, Xiuhua; Yang, Zhanmin

    2017-01-01

    Abstract Pain is prevalent in advanced malignancies; however, some patients cannot get adequate pain relief by conservative routes of analgesic administration or experience serious side effects related to high dose of opioids. For those who have exhausted multimodal conservative analgesic, intrathecal drug delivery is an alternative intervention for truly effective pain management. The objective of this study was to evaluate the clinical efficacy and safety of intrathecal drug delivery system (IDDS) for the treatment of intractable pain in advanced cancer patients. A prospective cohort study was performed between July 2015 and October 2016. Fifty-three patients undergoing intractable cancer-related pain or intolerable drug-related adverse effects were recruited and received IDDS therapy with a patient-controlled intrathecal analgesia pump. The assessment was conducted during admission, in titration period, and followed up monthly to death by scheduled refill visits. Pain numeric rating scale scores, comprehensive toxicity scores, quality of life scores, systemic opioid use (basal and breakthrough dose), intrathecal morphine use (basal and patient-controlled intrathecal analgesia dose), and complications were recorded to evaluate the curative effect and safety. Between baseline and all subsequent follow-ups, statistically significant decreases in pain numeric rating scale scores and comprehensive toxicity scores were verified. A statistical improvement in quality of life scores was found after starting IDDS therapy. Both basal and breakthrough doses of systemic opioid showed a significant decrease during the follow-up period. And there was a modest escalation in the intrathecal morphine dose throughout the duration of study. No infective, device-related, and catheter-related complications were observed. The findings showed that IDDS therapy allowed for rapid and highly effective pain relief with less toxicity in comparison to conservative medications. Patients with

  13. Parkinson's Disease: The Newest Advances

    MedlinePlus

    ... on genetic findings, investigators have already developed improved animal models, so essential for our understanding of what causes the disease and for testing new treatments, and have made breakthroughs in cell ...

  14. Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma.

    PubMed

    Okano, Yudai; Satoh, Tetsurou; Horiguchi, Kazuhiko; Toyoda, Minoru; Osaki, Aya; Matsumoto, Shunichi; Tomaru, Takuya; Nakajima, Yasuyo; Ishii, Sumiyasu; Ozawa, Atsushi; Shibusawa, Nobuyuki; Shimada, Takehiro; Higuchi, Tetsuya; Chikamatsu, Kazuaki; Yamada, Masanobu

    2016-10-29

    The anti-programmed cell death-1 monoclonal antibody (mab), nivolumab has recently been approved for the treatment of unresectable or metastatic malignant melanoma and non-small-cell lung cancers in Japan. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 mab for malignant melanoma that was approved earlier than nivolumab in Western countries, is known to frequently cause endocrine immune-related adverse events such as hypophysitis and thyroid dysfunction. We herein report a patient with advanced melanoma who appeared to develop hypophysitis as a consequence of the inhibition of PD-1 by nivolumab. One week after the 6(th) administration of nivolumab, the patient developed progressive fatigue and appetite loss. Laboratory data on admission for the 7(th) administration of nivolumab showed eosinophilia and hyponatremia. Since ACTH and cortisol levels were low, nivolumab was discontinued and a large dose of hydrocortisone (100 mg/d) was promptly administered intravenously. A magnetic resonance imaging scan revealed the mild enlargement of the anterior pituitary gland and thickening of the stalk with homogenous contrast. A detailed assessment of anterior pituitary functions with hypothalamic hormone challenges showed that hormonal secretions other than ACTH and TSH were normal. With a replacement dose of hydrocortisone (20 mg/d), the 7(th) administration of nivolumab was completed without exacerbating the patient's general condition. The present report provides the first detailed endocrinological presentation of nivolumab-induced hypophysitis showing the enlargement of the pituitary gland and stalk in a malignant melanoma patient in Japan. Oncologists and endocrinologists need to be familiar with potentially life-threatening hypophysitis induced by immune-checkpoint inhibitors.

  15. Updates in adult-onset Still disease: Atypical cutaneous manifestations and associations with delayed malignancy.

    PubMed

    Sun, Natalie Z; Brezinski, Elizabeth A; Berliner, Jacqueline; Haemel, Anna; Connolly, M Kari; Gensler, Lianne; McCalmont, Timothy H; Shinkai, Kanade

    2015-08-01

    Adult-onset Still disease (AOSD) is a systemic inflammatory disorder that is clinically characterized by a heterogeneous constellation of symptoms and signs. Though an evanescent eruption is the classic cutaneous finding, recent literature has highlighted atypical rashes associated with Still disease. A second emerging concept in presentations of AOSD is its association with malignancy. This review focuses on these concepts: the clinical spectrum of atypical skin manifestations and AOSD as a paraneoplastic phenomenon. PubMed-MEDLINE was screened for peer-reviewed articles describing atypical presentations of AOSD and cases associated with malignancy. Erythematous, brown or violaceous, persistent papules and plaques were the most common cutaneous finding (28/30 [93%]). Linear configurations were also rarely described. Of these patients, 81% concurrently had the typical evanescent skin eruption. There were 31 patients with associated malignancies, most commonly breast cancer and lymphoma. The diagnosis of malignancy did not precede or immediately follow a clinical presentation otherwise consistent with AOSD in a considerable subset of patients (42%). Understanding the cutaneous spectrum of AOSD and heightened awareness for its delayed association with malignancy may lead to improved recognition of cutaneous variants and reinforce the need for diagnostic evaluation and long-term follow-up for malignancy in patients with this clinical presentation.

  16. 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.

  17. 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

  18. 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

  19. [Advances in sickle cell disease].

    PubMed

    de Montalembert, Mariane

    2008-10-01

    Generation of transgenic mice have identified new pathophysiological mechanisms in sickle disease, including a permanent proinflammatory state and dysregulation of vascular tone. Treatment is no longer solely symptomatic. New agents target red cell hydration and the kinetics of deoxyhemoglobin S polymerization. Hydroxyurea, which reactivates fetal hemoglobin synthesis, is now widely used. Anti-adhesion molecules and agents modulating vascular tone are being tried in sickle mice. Bone marrow transplantation is widely used to cure patients with HLA-identical siblings, and gene therapy looks promising for those without a donor.

  20. 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.

  1. Pulmonary talc granulomatosis mimicking malignant disease 30 years after last exposure: a case report

    PubMed Central

    Krimsky, William S; Dhand, Suneel

    2008-01-01

    Introduction Pulmonary talc granulomatosis is a rare disorder characterized by the development of foreign body granuloma secondary to talc exposure. Previous case reports have documented the illness in current intravenous drug users who inject medications intended for oral use. We present a rare case of the disease in a patient with a distant history of heroin abuse who presented initially with history and imaging findings highly suggestive of malignancy. Case presentation A 53-year-old man reported a 4-month history of increasing dyspnea and weight loss. He had a long history of smoking and admission chest X-ray revealed a density in the right hemithorax. Computed tomography confirmed a probable mass with further speculated opacities in both lung fields suspicious for malignant spread. Biopsies obtained using endobronchial ultrasound-guided aspiration returned negative for malignancy and showed bronchial epithelial cells with foreign body giant cell reaction and polarizable birefringent talc crystals. Conclusion This case demonstrates a rare presentation of talc granulomatosis three decades after the last likely exposure. The history and imaging findings in a chronic smoker were initially strongly suggestive of malignant disease, and we recommend that talc-induced lung disease is considered in any patient with multiple scattered pulmonary lesions and a history of intravenous drug use. Confirmation of the disease by biopsy is essential, but unfortunately there are few successful proven management options for patients with worsening disease. PMID:18598367

  2. IgG4-related Kidney Disease Mimicking Malignant Ureter Tumor: Case Report and Literature Review.

    PubMed

    Lei, Wen-Hui; Xin, Jun; Shao, Chu-Xiao; Mao, Ming-Feng; Zhu, Chao-Yong; Wu, Chui-Fen; Jin, Lie

    2016-01-01

    Immunoglobulin G4-related disease is a recently recognized systemic disease that can affect any organ or tissue in the body, including the kidneys. IgG4-related kidney disease (IgG4-RKD) is an important part of immunoglobulin G4-related disease. The most common renal manifestation of IgG4-RKD is tubulointerstitial nephritis and glomerular lesions. There, however, is few case of IgG4-RKD mimicking malignant ureter tumor leading to severe hydronephrosis. We herein report an unusual case of IgG4-RKD mimicking malignancy.A 66-year-old Asian man presented to the nephrologist with soreness of loins, anorexia, and acute kidney injury in 2010. His renal function spontaneously improved after 2 weeks' hemodialysis without systemic steroid therapy. Four years later, he presented to the urologist with severe left hydronephrosis because of marked thickness of the left ureter wall. As a ureteral malignancy could not be ruled out, laparoscopic nephroureterectomy was performed.IgG4-related kidney disease was confirmed by the histologic examination. Then, repeat laboratory test showed almost complete recovery of renal function after initiation of steroidal therapy.This case highlights the rare possibility of IgG4-RKD mimicking malignant ureter tumor. Nephrologist and pathologists should be aware of the possibility that hydronephrosis with ureter obstruction may be involved in IgG4-RKD.

  3. Advanced magnetic resonance imaging of neurodegenerative diseases.

    PubMed

    Agosta, Federica; Galantucci, Sebastiano; Filippi, Massimo

    2017-01-01

    Magnetic resonance imaging (MRI) is playing an increasingly important role in the study of neurodegenerative diseases, delineating the structural and functional alterations determined by these conditions. Advanced MRI techniques are of special interest for their potential to characterize the signature of each neurodegenerative condition and aid both the diagnostic process and the monitoring of disease progression. This aspect will become crucial when disease-modifying (personalized) therapies will be established. MRI techniques are very diverse and go from the visual inspection of MRI scans to more complex approaches, such as manual and automatic volume measurements, diffusion tensor MRI, and functional MRI. All these techniques allow us to investigate the different features of neurodegeneration. In this review, we summarize the most recent advances concerning the use of MRI in some of the most important neurodegenerative conditions, putting an emphasis on the advanced techniques.

  4. Malignant ameloblastoma: concurrent presentation of primary and distant disease and review of the literature.

    PubMed

    Berger, Aaron J; Son, Ji; Desai, Nikhil K

    2012-10-01

    Malignant ameloblastoma is a rare tumor of odontogenic origin with a metastatic focus. Distant metastatic disease is found most commonly in the lungs. A review of the literature shows that most cases of malignant ameloblastoma involve a disease-free period from primary tumor extirpation to the discovery of metastasis. This report describes the case of a 56-year-old man presenting with ameloblastoma of the maxilla and a solitary pulmonary metastasis concurrently. This represents a rare case in which there is a simultaneous diagnosis of primary ameloblastoma and a metastatic lesion. Appropriate workup for ameloblastoma includes surveillance for metastatic disease. Surgical resection of primary and distant disease is recommended. Chemotherapy and radiation may play a role in palliation when resection of metastatic disease is not feasible.

  5. Advanced imaging in equine dental disease.

    PubMed

    Selberg, Kurt; Easley, Jeremiah T

    2013-08-01

    Dental and sinus disorders are relatively common and of major clinical importance in equine medicine. Advanced diagnostic imaging has become an integral part of equine veterinary medicine. Advanced imaging has progressed the understanding, diagnosis, and treatment of dental- and sinus-related diseases. As a clinician, it is important to realize the value of advanced diagnostic imaging. Although computed tomography and magnetic resonance imaging are both significantly more expensive compared with other diagnostic tools, the financial cost of inaccurate diagnosis and treatment can often result in higher overall costs.

  6. Squamous cell carcinoma of the eyelid masquerading as 'malignant' ophthalmopathy of Graves's disease.

    PubMed Central

    Ford, H C; Delahunt, J W; Teague, C A

    1983-01-01

    A patient with Graves's disease is described in whom the periorbital changes of severe ophthalmopathy and iatrogenic Cushing's syndrome delayed the diagnosis of a squamous cell carcinoma of the eyelid. It is suggested that the immunosuppressive therapy which the patient received may have enhanced the growth of a pre-existing malignancy. Images PMID:6688354

  7. Malignant Rheumatic Heart Disease Presenting as Quadrivalvular Stenosis

    PubMed Central

    Sinha, Santosh Kumar; Thakur, Ramesh; Krishna, Vinay; Varma, Chandra Mohan; Goel, Amit; Jha, Mukesh Jitendra; Kumar, Ashutosh; Mishra, Vikas; Tiwari, Pradyot; Sinha, Rupesh

    2015-01-01

    Rheumatic disease may involve the pulmonary valve, but is exceedingly rare. Simultaneous involvement of all four valves is more likely to be the result of combination of causes, such as congenital, rheumatic, infective or degenerative disease. A unitary cause for quadrivalvular involvement would be either rheumatic or myxomatous degeneration. A 16-year-old young boy presented with progressive exertional dyspnea for the past 3 years. On evaluation, he was in atrial fibrillation with congestive heart failure. On examination, evidence of stenosis of the mitral, aortic and tricuspid valves with a history of rheumatic fever in childhood was revealed. Transthoracic echocardiography showed the quadrivalvular involvement. Only few reports are available in the literature describing rheumatic quadrivalvar damage and that too in third and fourth decade. This is probably first to be reported in juvenile age group. PMID:28197258

  8. 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.

  9. Serum sialic acid in malignant tumors, bacterial infections, and chronic liver diseases.

    PubMed

    Stefenelli, N; Klotz, H; Engel, A; Bauer, P

    1985-01-01

    The total serum sialic acid concentration was determined in 2,264 persons with various malignant tumors, bacterial infections, rheumatic diseases, and chronic liver diseases, and in a control group. The thiobarbiturate method according to Warren was used. The upper limit (95% percentile) in the control group was 2.23 mumol/ml. Higher values were found in the groups with neoplasms (mean: 3.04 mumol/ml), inflammatory diseases (e.g., pneumonia: 3.02 mumol/ml), and active rheumatoid arthritis (3.05 mumol/ml). In the group with malignant diseases, the sialic acid concentration at the time of diagnosis was highest for bronchial carcinoma (3.29 mumol/ml) and lowest for breast cancer (2.58 mumol/ml). In chronic liver diseases the mean sialic acid level was lower than in a heterogeneous group of noninflammatory and nonneoplastic diseases. The estimation of the serum sialic acid concentration could be useful in the detection of tumor burden and metastases, and in the evaluation of the later course and prognosis of malignant neoplasms if bacterial/inflammatory and active rheumatoid processes can be excluded.

  10. Methods of minimal residual disease (MRD) detection in childhood haematological malignancies.

    PubMed

    Jółkowska, Justyna; Derwich, Katarzyna; Dawidowska, Małgorzata

    2007-01-01

    The appropriate management of haematological disorders must rely on a precise and long-term monitoring of the patient's response to chemotherapy and radiotherapy. Clinical data are not sufficient and that is why in the last decade it became the most important to improve the knowledge of haematological diseases on the basis of molecular techniques and molecular markers. The presence of residual malignant cells among normal cells is termed minimal residual disease (MRD). Nowadays a great progress has been made in the treatment of malignant diseases and in the development of reliable molecular techniques, which are characterised by high sensitivity (10-3- 10-6) and ability to distinguish between normal and malignant cells at diagnosis and during follow-up. Especially, MRD data based on quantitative analysis (RQ-PCR, RT-RQ-PCR) appear to be crucial for appropriate evaluation of treatment response in many haematological malignancies. Implementation of standardized approaches for MRD assessment into routine molecular diagnostics available in all oncohaematological centres should be regarded nowadays a crucial point in further MRD study development.

  11. 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.

  12. 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.

  13. Advances in the in Vivo Raman Spectroscopy of Malignant Skin Tumors Using Portable Instrumentation.

    PubMed

    Kourkoumelis, Nikolaos; Balatsoukas, Ioannis; Moulia, Violetta; Elka, Aspasia; Gaitanis, Georgios; Bassukas, Ioannis D

    2015-06-26

    Raman spectroscopy has emerged as a promising tool for real-time clinical diagnosis of malignant skin tumors offering a number of potential advantages: it is non-intrusive, it requires no sample preparation, and it features high chemical specificity with minimal water interference. However, in vivo tissue evaluation and accurate histopathological classification remain a challenging task for the successful transition from laboratory prototypes to clinical devices. In the literature, there are numerous reports on the applications of Raman spectroscopy to biomedical research and cancer diagnostics. Nevertheless, cases where real-time, portable instrumentations have been employed for the in vivo evaluation of skin lesions are scarce, despite their advantages in use as medical devices in the clinical setting. This paper reviews the advances in real-time Raman spectroscopy for the in vivo characterization of common skin lesions. The translational momentum of Raman spectroscopy towards the clinical practice is revealed by (i) assembling the technical specifications of portable systems and (ii) analyzing the spectral characteristics of in vivo measurements.

  14. Advances in the in Vivo Raman Spectroscopy of Malignant Skin Tumors Using Portable Instrumentation

    PubMed Central

    Kourkoumelis, Nikolaos; Balatsoukas, Ioannis; Moulia, Violetta; Elka, Aspasia; Gaitanis, Georgios; Bassukas, Ioannis D.

    2015-01-01

    Raman spectroscopy has emerged as a promising tool for real-time clinical diagnosis of malignant skin tumors offering a number of potential advantages: it is non-intrusive, it requires no sample preparation, and it features high chemical specificity with minimal water interference. However, in vivo tissue evaluation and accurate histopathological classification remain a challenging task for the successful transition from laboratory prototypes to clinical devices. In the literature, there are numerous reports on the applications of Raman spectroscopy to biomedical research and cancer diagnostics. Nevertheless, cases where real-time, portable instrumentations have been employed for the in vivo evaluation of skin lesions are scarce, despite their advantages in use as medical devices in the clinical setting. This paper reviews the advances in real-time Raman spectroscopy for the in vivo characterization of common skin lesions. The translational momentum of Raman spectroscopy towards the clinical practice is revealed by (i) assembling the technical specifications of portable systems and (ii) analyzing the spectral characteristics of in vivo measurements. PMID:26132563

  15. Giant Malignant Pheochromocytoma with Palpable Rib Metastases

    PubMed Central

    Gokce, Gokhan; Kilicli, Fatih; Elagoz, Sahande; Ayan, Semih; Gultekin, Emin Yener

    2014-01-01

    Pheochromocytoma is a rare and usually benign neuroendocrine neoplasm. Only 10% of all these tumors are malignant and there are no definitive histological or cytological criteria of malignancy. Single malignancy criteria are the presence of advanced locoregional disease or metastases. We report a case, with a giant retroperitoneal tumor having multiple metastases including palpable rib metastases, who was diagnosed as a malignant pheochromocytoma. The patient was treated with surgery. The literature was reviewed to evaluate tumor features and current diagnostic and therapeutic approaches for patients with metastatic or potentially malignant pheochromocytoma. PMID:25152826

  16. Competing events in patients with malignant disease who are at risk for recurrent venous thromboembolism.

    PubMed

    Parpia, S; Julian, J A; Thabane, L; Lee, A Y Y; Rickles, F R; Levine, M N

    2011-11-01

    Patients with malignant disease enrolled in trials of thrombotic disorders may experience competing events such as death. The occurrence of a competing event may prevent the thrombotic event from being observed. Standard survival analysis techniques ignore competing risks, resulting in possible bias and distorted inferences. To assess the impact of competing events on the results of a previously reported trial comparing low molecular weight heparin (LMWH) with oral anticoagulant (OAC) therapy for the prevention of recurrent venous thromboembolism (VTE) in patients with advanced cancer, we compare the results from standard survival analysis with those from competing risk techniques which are based on the cumulative incidence function (CIF) and Gray's test. The Kaplan-Meier method overestimates the risk of recurrent VTE (17.2% in the OAC group and 8.7% in the LMWH group). Risk of recurrence using the CIF is 12.0% and 6.0% in the OAC and LMWH groups, respectively. Both the log-rank test (p=0.002) and Gray's test (p=0.006) suggest evidence in favor of LMWH. The overestimation of risk is 30% in each treatment group, resulting in a similar relative treatment effect; using the Cox model the hazard ratio (HR) is 0.48 (95% confidence interval [CI], 0.30 to 0.78) and HR=0.47 (95% CI, 0.29 to 0.74) using the CIF model. Failing to account for competing risks may lead to incorrect interpretations of the probability of recurrent VTE. However, when the distribution of competing risks is similar within each treatment group, standard and competing risk methods yield comparable relative treatment effects.

  17. 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

  18. Alzheimer's disease: research advances and medical reality.

    PubMed

    Seiguer, Erica

    2005-07-01

    Alzheimer's disease was the eighth-leading cause of death in 2001. There is no cure and no effective treatment. Alzheimer's disease presents policy-makers with several challenges, including the level of funding and direction of federally funded research, as well as the cost pressures on Medicare and Medicaid of long-term care. These challenges will increase in intensity as demographic changes, particularly the aging of baby boomers, take hold. Better prevention of Alzheimer's, advances in therapy, and appropriate care modalities will likely require significant investment.

  19. Cutaneous mucormycosis in advanced HIV disease.

    PubMed

    Moreira, José; Ridolfi, Felipe; Almeida-Paes, Rodrigo; Varon, Andrea; Lamas, Cristiane C

    Angionvasive mucormycosis is an emerging fungal disease known to affect mainly diabetics or subjects with profound neutropenia. Infection usually occurs through the inhalation route, but cutaneous inoculation may occur after trauma or burns. However, mucormycosis remains unusual in HIV infection. We report a fatal case of cutaneous mucormycosis due to Rhizopus arrhizus involving the scalp following herpes zoster infection. The patient was a 42-year-old man with advanced AIDS failing on salvage antiretroviral therapy. The fungus was diagnosed on the basis of histopathology and culture. Our case emphasizes the need to consider mucormycosis in the differential diagnosis of necrotic cutaneous lesions in patients with late-stage HIV disease.

  20. Sialadenosis in Patients with Advanced Liver Disease

    PubMed Central

    Close, John M.; Eghtesad, Bijan

    2009-01-01

    Sialadenosis (sialosis) has been associated most often with alcoholic liver disease and alcoholic cirrhosis, but a number of nutritional deficiencies, diabetes, and bulimia have also been reported to result in sialadenosis. The aim of this study was to determine the prevalence of sialadenosis in patients with advanced liver disease. Patients in the study group consisted of 300 candidates for liver transplantation. Types of liver disease in subjects with clinical evidence of sialadenosis were compared with diagnoses in cases who had no manifestations of sialadenosis. The data were analyzed for significant association. Sialadenosis was found in 28 of the 300 subjects (9.3%). Among these 28 cases, 11 (39.3%) had alcoholic cirrhosis. The remaining 17 (60.7%) had eight other types of liver disease. There was no significant association between sialadenosis and alcoholic cirrhosis (P = 0.389). These findings suggest that both alcoholic and non-alcoholic cirrhosis may lead to the development of sialadenosis. Advanced liver disease is accompanied by multiple nutritional deficiencies which may be exacerbated by alcohol. Similar metabolic abnormalities may occur in patients with diabetes or bulimia. Malnutrition has been associated with autonomic neuropathy, the pathogenic mechanism that has been proposed for sialadenosis. PMID:19644542

  1. Sialadenosis in patients with advanced liver disease.

    PubMed

    Guggenheimer, James; Close, John M; Eghtesad, Bijan

    2009-06-01

    Sialadenosis (sialosis) has been associated most often with alcoholic liver disease and alcoholic cirrhosis, but a number of nutritional deficiencies, diabetes, and bulimia have also been reported to result in sialadenosis. The aim of this study was to determine the prevalence of sialadenosis in patients with advanced liver disease. Patients in the study group consisted of 300 candidates for liver transplantation. Types of liver disease in subjects with clinical evidence of sialadenosis were compared with diagnoses in cases who had no manifestations of sialadenosis. The data were analyzed for significant association. Sialadenosis was found in 28 of the 300 subjects (9.3%). Among these 28 cases, 11 (39.3%) had alcoholic cirrhosis. The remaining 17 (60.7%) had eight other types of liver disease. There was no significant association between sialadenosis and alcoholic cirrhosis (P = 0.389). These findings suggest that both alcoholic and non-alcoholic cirrhosis may lead to the development of sialadenosis. Advanced liver disease is accompanied by multiple nutritional deficiencies which may be exacerbated by alcohol. Similar metabolic abnormalities may occur in patients with diabetes or bulimia. Malnutrition has been associated with autonomic neuropathy, the pathogenic mechanism that has been proposed for sialadenosis.

  2. Pneumocystis carinii antigenemia in adults with malignancy, infection, or pulmonary disease.

    PubMed Central

    Pifer, L L; Niell, H B; Morrison, B J; Counce, J D; Freeman, J M; Woods, D R; Neely, C L

    1984-01-01

    A counterimmunoelectrophoresis test for Pneumocystis carinii antigenemia was employed to assess the extent of subclinical infection or colonization with this agent in adults with infection, pulmonary disease, or malignancy and in healthy homosexual men. Antigenemia was detected in 6 of 208 (3%) of normal controls, 3 of 28 (11%) of patients with pulmonary infection, 3 of 33 (9%) of those with chronic lung disease, 1 of 36 (3%) of patients with lung cancer, 7 of 271 (3%) of afebrile subjects with malignancy, 6 of 19 (32%) of febrile patients with malignancy, 2 of 22 (9%) of those with nonpulmonary infection, and 0 of 21 (0%) of healthy young homosexual men. These data suggest that P. carinii is a common commensal or saprophyte that becomes clinically significant only when host defenses are impaired. Antigenemia may occur intermittently during various disease states in the absence of positive clinical signs and should alert the physician to subacute infection or colonization. Treatment appears advisable when clinical data and counterimmunoelectrophoresis results concur. PMID:6334694

  3. 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

  4. Myeloma Today: Disease Definitions and Treatment Advances

    PubMed Central

    Rajkumar, S. Vincent

    2015-01-01

    There have been major advances in the diagnosis, staging, risk-stratification, and management of multiple myeloma (MM). In addition to established CRAB (hypercalcemia, renal failure, anemia, and lytic bone lesions) features, new diagnostic criteria include 3 new biomarkers to diagnose the disease: bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain ratio ≥100, and >1 focal lesion on magnetic resonance imaging. MM can be classified into several subtypes based on baseline cytogenetics, and prognosis varies according to underlying cytogenetic abnormalities. A Revised International Staging System has been developed which combines markers of tumor burden (albumin, beta-2 microglobulin) with markers of aggressive disease biology (high risk cytogenetics and elevated serum lactate dehydrogenase). Although the approach to therapy remains largely the same, the treatment options at every stage of the disease have changed. Carfilzomib, pomalidomide, and panobinostat have been approved for the treatment of the disease. Elotuzumab, daratumumab, and ixazomib are expected to be approved shortly. These drugs combined with older agents such as cyclophosphamide, dexamethasone, thalidomide, bortezomib, and lenalidomide dramatically increase the repertoire of regimens available for the treatment of MM. This review provides a concise overview of recent advances in MM, including updates to diagnostic criteria, staging, risk-stratification, and management. PMID:26565896

  5. New Advances in Polycystic Liver Diseases.

    PubMed

    Santos-Laso, A; Izquierdo-Sánchez, L; Lee-Law, P Y; Perugorria, M J; Marzioni, M; Marin, J J G; Bujanda, L; Banales, J M

    2017-02-01

    Polycystic liver diseases (PLDs) include a heterogeneous group of congenital disorders inherited as dominant or recessive genetic traits; they are manifested alone or in association with polycystic kidney disease. Ductal plate malformation during embryogenesis and the loss of heterozygosity linked to second-hit mutations may promote the dilatation and/or development of a large number (> 20) of biliary cysts, which are the main cause of morbidity in these patients. Surgical procedures aimed to eliminate symptomatic cysts show short-term beneficial effects, but are not able to block the disease progression. Therefore, liver transplantation is the only curative option. Intense studies on the molecular mechanisms involved in the pathogenesis of PLDs have resulted in different clinical trials, some of them with promising outcomes. Here the authors summarize the key aspects of PLD etiology, pathogenesis, and therapy, highlighting the most recent advances and future research directions.

  6. Advance Care Planning in Patients with Primary Malignant Brain Tumors: A Systematic Review

    PubMed Central

    Song, Krystal; Amatya, Bhasker; Voutier, Catherine; Khan, Fary

    2016-01-01

    Advance care planning (ACP) is a process of reflection and communication of a person’s future health care preferences, and has been shown to improve end-of-life (EOL) care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumors (pmBT). A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus, and Web of Science) up to July 2016. Manual search of bibliographies of articles and gray literature search were also conducted. Two independent reviewers selected studies, extracted data, and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program’s appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included [1 randomized controlled trial (RCT), 17 cohort studies, 1 qualitative study] with 4686 participants. All studies scored “low to moderate” on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision-making. However, the effect of the intervention on quality of life and care at the EOL were unclear. There was a low rate of use of ACP discussions at the EOL. Advance directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with

  7. Advance Care Planning in Patients with Primary Malignant Brain Tumors: A Systematic Review.

    PubMed

    Song, Krystal; Amatya, Bhasker; Voutier, Catherine; Khan, Fary

    2016-01-01

    Advance care planning (ACP) is a process of reflection and communication of a person's future health care preferences, and has been shown to improve end-of-life (EOL) care for patients. The aim of this systematic review is to present an evidence-based overview of ACP in patients with primary malignant brain tumors (pmBT). A comprehensive literature search was conducted using medical and health science electronic databases (PubMed, Cochrane, Embase, MEDLINE, ProQuest, Social Care Online, Scopus, and Web of Science) up to July 2016. Manual search of bibliographies of articles and gray literature search were also conducted. Two independent reviewers selected studies, extracted data, and assessed the methodologic quality of the studies using the Critical Appraisal Skills Program's appraisal tools. All studies were included irrespective of the study design. A meta-analysis was not possible due to heterogeneity amongst included studies; therefore, a narrative analysis was performed for best evidence synthesis. Overall, 19 studies were included [1 randomized controlled trial (RCT), 17 cohort studies, 1 qualitative study] with 4686 participants. All studies scored "low to moderate" on the methodological quality assessment, implying high risk of bias. A single RCT evaluating a video decision support tool in facilitating ACP in pmBT patients showed a beneficial effect in promoting comfort care and gaining confidence in decision-making. However, the effect of the intervention on quality of life and care at the EOL were unclear. There was a low rate of use of ACP discussions at the EOL. Advance directive completion rates and place of death varied between different studies. Positive effects of ACP included lower hospital readmission rates, and intensive care unit utilization. None of the studies assessed mortality outcomes associated with ACP. In conclusion, this review found some beneficial effects of ACP in pmBT. The literature still remains limited in this area, with lack of

  8. Psychological stress, cancer incidence and mortality from non-malignant diseases.

    PubMed Central

    Johansen, C.; Olsen, J. H.

    1997-01-01

    Psychological stress has been claimed to contribute to the onset of cancer and to increase mortality from a number of non-malignant diseases. We investigated the effect of a genuine psychological stressor, i.e. cancer in a child, on the incidence of cancer and mortality from non-malignant diseases of 11,231 parents in a Danish nationwide population-based study. The children were identified from records in the Danish Cancer Registry for the period 1943-85; their parents were identified from population registers. Overall, 1665 parental malignancies were diagnosed from the date the cancer of the child was reported until 1992, compared with 1702 expected from national incidence rates, yielding standardized incidence ratios of 1.0 (95% confidence interval, 0.9-1.0) for all parents, 1.0 for mothers and 1.0 for fathers. No statistically significant deviation of the relative risk from unity was seen for any period of follow-up after the stressful event, and no excess risk was seen for any particular type of cancer. Moreover, a total of 2137 parental deaths were observed over the period 1974-92, compared with 2333 expected from national mortality rates, giving an overall standardized mortality ratio of 0.9 (range 0.9-1.0). No excess mortality was seen from causes associated with allergic illness, autoimmune conditions, chronic illness or changes in behaviour. Our data provide no support for the hypothesis of an association between psychological stress and the incidence of cancer or mortality from non-malignant diseases. We conclude that the human organism is highly adaptable, even to extreme psychological stress. PMID:9000613

  9. Malignant peritoneal mesothelioma

    PubMed Central

    Munkholm-Larsen, Stine; Cao, Christopher Q; Yan, Tristan D

    2009-01-01

    Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM) represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. The great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This remarkable improvement in survival has prompted new search into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade. PMID:21160794

  10. Second lymphoid malignant neoplasms occurring in patients treated for Hodgkin's disease

    SciTech Connect

    Armitage, J.O.; Dick, F.R.; Goeken, J.A.; Foucar, M.K.; Gingrich, R.D.

    1983-03-01

    Patients who have been treated for Hodgkin's disease are at increased risk for second malignant neoplasms, particularly acute nonlymphoblastic leukemia and non-Hodgkin's lymphoid malignant neoplasms (NHLMs). We diagnosed five cases of NHLM in 242 patients initially treated for Hodgkin's disease between 1973 and 1980, giving a minimum incidence for this occurrence of 2.1%. The initial therapy for Hodgkin's disease, irradiation in three patients and chemotherapy in two patients, resulted in a complete remission in each case. The NHLM appeared 12, 13, 26, 30, and 54 months after the diagnosis of Hodgkin's disease. The cell type of NHLM and immunologic phenotype were as follows: large cell, immunoblastic T; large cell, immunoblastic null; large cell, cleaved and noncleaved B; large cell, cleaved and noncleaved (not studied); and lymphoblastic T. A review of 24 other cases of NHLMs, occurring in patients treated for Hodgkin's disease, reported in the literature, confirm the morphologic and immunologic heterogeneity. The poor response to therapy in our patients and those previously described demonstrate the seriousness of this phenomenon.

  11. Postoperative Depression of Tumour-directed Cell-mediated Immunity in Patients with Malignant Disease

    PubMed Central

    Cochran, A. J.; Spilg, W. G. S.; Mackie, Rona M.; Thomas, Catherine E.

    1972-01-01

    Leucocytes from 46 melanoma patients, 45 breast carcinoma patients, and 95 control donors were tested by the leucocyte migration test against the supernatants of homogenates of malignant melanomas, breast carcinomas, simple breast tumours, and breasts showing simple cystic disease. By comparison with controls inhibition of migration occurred significantly more frequently when tumour patients' leucocytes were exposed to extracts of histogenetically similar tumours. Cell-mediated immunity to tumour-associated antigens was measured in 12 patients with breast carcinoma and 12 with malignant melanoma immediately before surgical operation and in the postoperative period. All patients tested before operation showed significant inhibition of migration on contact with extracts of histogenetically similar tumours. Postoperatively the degree of leucocyte migration inhibition was reduced in all patients with melanoma and breast carcinoma. Significant inhibition of leucocyte migration returned in most patients 6-22 days after operation. PMID:5077468

  12. Immunotherapy of Malignant Disease Using Chimeric Antigen Receptor Engrafted T Cells

    PubMed Central

    Maher, John

    2012-01-01

    Chimeric antigen receptor- (CAR-) based immunotherapy has been under development for almost 25 years, over which period it has progressed from a new but cumbersome technology to an emerging therapeutic modality for malignant disease. The approach involves the genetic engineering of fusion receptors (CARs) that couple the HLA-independent binding of cell surface target molecules to the delivery of a tailored activating signal to host immune cells. Engineered CARs are delivered most commonly to peripheral blood T cells using a range of vector systems, most commonly integrating viral vectors. Preclinical refinement of this approach has proceeded over several years to the point that clinical testing is now being undertaken at several centres, using increasingly sophisticated and therapeutically successful genetic payloads. This paper considers several aspects of the pre-clinical and clinical development of CAR-based immunotherapy and how this technology is acquiring an increasing niche in the treatment of both solid and haematological malignancies. PMID:23304553

  13. A Risk Prediction Score for Invasive Mold Disease in Patients with Hematological Malignancies

    PubMed Central

    Stanzani, Marta; Lewis, Russell E.; Fiacchini, Mauro; Ricci, Paolo; Tumietto, Fabio; Viale, Pierluigi; Ambretti, Simone; Baccarani, Michele; Cavo, Michele; Vianelli, Nicola

    2013-01-01

    Background A risk score for invasive mold disease (IMD) in patients with hematological malignancies could facilitate patient screening and improve the targeted use of antifungal prophylaxis. Methods We retrospectively analyzed 1,709 hospital admissions of 840 patients with hematological malignancies (2005-2008) to collect data on 17 epidemiological and treatment-related risk factors for IMD. Multivariate regression was used to develop a weighted risk score based on independent risk factors associated with proven or probable IMD, which was prospectively validated during 1,746 hospital admissions of 855 patients from 2009-2012. Results Of the 17 candidate variables analyzed, 11 correlated with IMD by univariate analysis, but only 4 risk factors (neutropenia, lymphocytopenia or lymphocyte dysfunction in allogeneic hematopoietic stem cell transplant recipients, malignancy status, and prior IMD) were retained in the final multivariate model, resulting in a weighted risk score 0-13. A risk score of < 6 discriminated patients with low (< 1%) versus higher incidence rates (> 5%) of IMD, with a negative predictive value (NPV) of 0.99, (95% CI 0.98-0.99). During 2009-2012, patients with a calculated risk score at admission of < 6 had significantly lower 90-day incidence rates of IMD compared to patients with scores > 6 (0.9% vs. 10.6%, P <0.001). Conclusion An objective, weighted risk score for IMD can accurately discriminate patients with hematological malignancies at low risk for developing mold disease, and could possibly facilitate “screening-out” of low risk patients less likely to benefit from intensive diagnostic monitoring or mold-directed antifungal prophylaxis. PMID:24086555

  14. 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

  15. Management of thrombocytopenia in advanced liver disease.

    PubMed

    Gangireddy, V G R; Kanneganti, P C; Sridhar, S; Talla, S; Coleman, T

    2014-11-01

    Thrombocytopenia (defined as a platelet count <150×10(9)) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×10(9) to 75×10(9)) 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.

  16. Overexpression of DCLK1 is predictive for recurrent disease in major salivary gland malignancies.

    PubMed

    Kadletz, Lorenz; Aumayr, Klaus; Heiduschka, Gregor; Schneider, Sven; Enzenhofer, Elisabeth; Lill, Claudia

    2017-01-01

    Salivary gland carcinomas are a rare malignancy. Therefore, little is known about biomarkers and cancer stem cells in salivary gland malignancies. Double cortin-like kinase 1 (DCLK1) is a promising therapeutic target and cancer stem cell marker, predominantly investigated in pancreatic and colorectal cancer. The purpose of this study was to investigate the expression of DCLK1 in major and minor salivary gland carcinomas and its influence on survival. We examined a total of 80 patients with major or minor salivary gland cancer in this retrospective study. Immunohistochemistry with anti-DCLK1 antibody was applied to assess the expression of DCLK1. Moreover, we evaluated the impact of DCLK1 on overall and disease-free survival. DCLK1 expression could be detected in 66.3 % of all examined cases. Overexpression of DCLK1 was associated with reduced overall and disease-free survival in patients with major salivary gland cancer. Disease-free survival reached statistical significance (p = 0.0107). However, expression of DCLK1 had no influence on survival in patients with minor salivary gland cancer. Since treatment of recurrent disease in oncologic patients is utterly challenging, DCLK1 may be a promising prognostic biomarker that helps to identify patients with a high risk for recurrence of major salivary gland carcinoma.

  17. Disparity Expression of Notch1 in Benign and Malignant Colorectal Diseases

    PubMed Central

    Huang, Rui; Tang, Qingchao; You, Qi; Liu, Zheng; Wang, Guiyu; Chen, Yinggang; Sun, Yuwen; Muhammad, Shan; Wang, Xishan

    2013-01-01

    Background and Objectives Although there was growing evidence supporting the hypothesis that Notch1 was one of the few candidate genes linked with colorectal cancer (CRC) susceptibility, the precise level of Notch1 protein expression in benign and malignant colorectal diseases was still unknown. Our study has investigated the Notch1 expression in benign and malignant colorectal diseases as well as to investigate the role and clinicopathological significance of aberrant expression of Notch1 in CRC. Methods The protein expression of Notch1 was examined by immunohistochemistry in 901 clinical specimens with colorectal diseases, including 220 patients with ulcerative colitis, 232 patients with colorectal adenoma and 449 patients with colorectal cancer. Associations between the expression of Notch1 and various clinicopathological features, as well as survival status, were studied. Results Cytoplasmic Notch1 was expressed in 7.7% of patients with ulcerative colitis, 14.7% of patients with colorectal adenoma and 58.0% of patients with colorectal cancer, respectively. Colorectal cancer patients with high expression levels of Notch1 showed lower overall survival (OS) and disease-free survival (DFS) rates than those patients with low Notch1 expression. Conclusions Expression level of Notch1 was gradually increased from precancerous lesions to cancer. It might play as an oncogene in the CRC development, and might be potentially used as a biomarker for prognosis of CRCs. PMID:24312514

  18. Small bowel metastasis from pancreatic cancer in a long-term survival patient with synchronous advanced malignant pleural mesothelioma: A case report and literature review

    PubMed Central

    Fasano, Morena; Corte, Carminia Maria Della; Vicidomini, Giovanni; Scotti, Valerio; Rambaldi, Pier Francesco; Fiorelli, Alfonso; Accardo, Marina; De Vita, Ferdinando; Santini, Mario; Ciardiello, Fortunato; Morgillo, Floriana

    2016-01-01

    Diffuse malignant pleural mesothelioma (MPM) is an aggressive tumor that originates from the surface of the pleura. Approximately 70% of cases are associated with chronic asbestos exposure. MPM is regarded as an incurable disease, with a median survival of ~2 years following intensive multimodality treatment. Pancreatic cancer is a malignancy also associated with a poor prognosis, with only 2% of patients surviving for 5 years. The majority of patients with pancreatic cancer are diagnosed with an advanced stage of disease and experience a poor response to therapy. The development of synchronous MPM and other types of cancer is rare. The present study describes a patient with synchronous, biphasic MPM and pancreatic adenocarcinoma, who was treated with a multimodal therapeutic approach with stereotactic body radiation therapy. Due to a suspected diagnosis of ‘acute abdomen’, an emergency small intestine resection was performed and a subsequent diagnosis of moderately-differentiated adenocarcinoma was confirmed. During a further immunohistochemical examination, pathologists determined that the small bowel metastasis descended from pancreatic cancer. The onset of bowel metastasis is an event rarely associated with MPM, and has not been previously described in the literature for cases of pancreatic cancer. Therefore, to the best of our knowledge, the present study describes the first case of intestinal metastasis from pancreatic cancer in a long-term survival patient with biphasic MPM. PMID:28105159

  19. Primary immunodeficiency diseases associated with increased susceptibility to viral infections and malignancies.

    PubMed

    Rezaei, Nima; Hedayat, Mona; Aghamohammadi, Asghar; Nichols, Kim E

    2011-06-01

    Primary immunodeficiencies (PIDs) are commonly characterized by an increased susceptibility to specific infections and, in certain instances, a higher than usual incidence of malignancies. Although improved diagnosis and early treatment of PIDs have reduced early morbidity and mortality from infection, the development of cancer remains a significant cause of premature death. The emergence of cancer in patients with PIDs often results from impairments in the immune response that lead to weakened surveillance against oncogenic viruses, premalignant or malignant cells, or both. Here we review the clinical and biologic features of several PIDs associated with enhanced susceptibility to viral infections and cancer, including X-linked lymphoproliferative disease; IL-2-inducible T-cell kinase deficiency; epidermodysplasia verruciformis; warts, hypogammaglobulinemia, infections, and myelokathexis syndrome; autosomal recessive hyper-IgE syndrome; X-linked agammaglobulinemia; and common variable immunodeficiency. It is of importance that we gain in-depth insights into the fundamental molecular nature of these unique PIDs to better understand the pathogenesis of virus-associated malignancies and to develop innovative therapeutic strategies.

  20. Pneumosinus Dilatans Helping Subcranial Resection in a Patient with Advanced Ethmoid Malignancy

    PubMed Central

    Joseph, Shawn T.; Thankappan, Krishnakumar; Buggaveeti, Rahul; Iyer, Subramania

    2014-01-01

    Subcranial approach is a useful procedure in the management of limited anterior skull base tumors. But the posterior and superior visualization may be limited, in ethmoid malignancies with a large intracranial extension. A 55-year-old male patient, a case of an ethmoid malignancy, with a large intracranial component was resected with adequate margins by a subcranial approach. The coincident pneumosinus dilatans helped the surgical resection. This case demonstrates that assessment of pneumatization of the frontal sinus is as important as the size and extent of the tumor, while deciding an anterior skull base surgical approach. Even large malignant lesions may be approached subcranially if the frontal sinus is proportionately large. Pneumosinus dilatans, though rare, can be used to the benefit of the patient in selecting a less invasive approach. PMID:26269730

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

    ClinicalTrials.gov

    2017-03-20

    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

  2. Disseminated Alveolar Hydatid Disease Resembling a Metastatic Malignancy: A Diagnostic Challenge—A Report of Two Cases

    PubMed Central

    Bulakci, Mesut; Cengel, Ferhat; Gocmez, Ahmet; Kartal, Merve Gulbiz; Isik, Emine Goknur; Celenk, Erhan

    2014-01-01

    Alveolar hydatid disease or alveolar echinococcosis is a disease of the parasite Echinococcus multilocularis that is potentially fatal if left untreated. It primarily involves the liver but can be disseminated to other organs like the lungs and the brain by hematogenous route. Multiorgan involvement and the aggressive appearance of lesions make alveolar hydatid disease easy to confuse with a metastatic malignancy. For this reason, histopathological confirmation is essential for definite diagnosis. We present the imaging features of this disease in two patients in order to emphasize that these lesions can be easily misdiagnosed as malignancies. PMID:25374743

  3. Comparison of Ga-67 planar imaging and single photon emission computed tomography in malignant chest disease

    SciTech Connect

    Tumeh, S.S.; Rosenthal, D.; Kaplan, W.D.; English, R.E.; Holman, B.L.

    1985-05-01

    To determine the value of Ga-67 single photon emission computed tomography (SPECT) in patients (pts) with malignant chest disease, the authors compared Ga-67 planar scans (ps) and SPECT with the medical records in twenty-five consecutive patients. Twenty-three examinations were performed on 17 pts with Hodgkin's disease (HD) and three pts with non-Hodgkin's lymphoma. Five examinations were performed on 5 pts with bronchogenic carcinoma (BC). The two modalities were evaluated for (1) presence or absence of disease, (2) number of foci of abnormal uptake and (3) extent of disease. In pts with lymphoma, SPECT defined the extent of disease better than planar imaging in eight examinations; it demonstrated para-cardial involvement in one pt, separated hilar from mediastinal disease in 4, and demonstrated posterior mediastinal disease in 3. SPECT clarified suspicious foci on planar images in seven examinations, correctly ruled out disease in two pts with equivocal planar images and did not exchange planar image findings in six examinations. In pts with bronchogenic carcinoma, both medalities correctly ruled out mediastinal involvement in three pts. SPECT detected mediastinal lymph node involvement in one pt with equivocal planar images. Both SPECT and planar imaging missed direct tumor extension to the mediastinum in one pt. They conclude that Ga-67 with SPECT is better than planar images for staging of chest lymphoma and BC. Since it defines different lymph node groups it carries a good potential for staging as well as follow up of those pts.

  4. 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.

  5. McCune-Albright syndrome mimicking malignancy: an endocrine disease from oncologist's perspective.

    PubMed

    Genç, D Bahar; Özkan, M Alp; Büyükgebiz, Atilla

    2012-09-01

    Fibrous dysplasia (FD) is categorized as either monostotic or polyostotic and may occur as a component of McCune-Albright syndrome (MAS). Imaging findings can mimic neoplastic diseases. We present a case of MAS initially suspected to have neoplastic disease. A 9-year-old girl was admitted to pediatric emergency with ataxia. Upon hospitalization, an extradural mass was seen on cranial magnetic resonance imaging (MRI) and the bone survey showed lytic lesions in the long bones. The patient was referred to the pediatric oncology department with a presumptive diagnosis of Langerhans cell histiocytosis or metastatic tumor. Further investigations demonstrated that the patient had MAS and coexisting postinfectious cerebellitis. The findings in this patient demonstrate that the radiographic findings and the clinical presentation of FD and MAS may be similar to those of malignant diseases.

  6. IgG4-related disease presenting with destructive sinonasal lesion mimicking malignancy.

    PubMed

    Chen, Bo-Nien

    2016-11-01

    IgG4-related disease is a newly recognized systemic fibroinflammatory disorder. We report a 36-year-old man who presented with intractable right nasal pain and frontal headache for 1 month. Computed tomography revealed an ill-defined lesion with bony erosion over the right anterior ethmoid sinus and middle turbinate. The lesion was resected through endoscopic anterior ethmoidectomy and middle turbinectomy. IgG4-related disease was definitively diagnosed according to histopathological features. Prednisolone was administered postoperatively. IgG4-related disease presenting with destructive sinonasal lesion mimicking malignancy is rare. Awareness is essential to avoid delayed diagnosis or unnecessary invasive intervention, because the disorder responds to glucocorticoid and immunosuppressant therapy.

  7. 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

  8. Advances in chronic obstructive pulmonary disease.

    PubMed

    McDonald, C F; Khor, Y

    2013-08-01

    Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation in the presence of identifiable risk factors. Inflammation is the central pathological feature in the pathogenesis of COPD. In addition to its pulmonary effects, COPD is associated with significant extrapulmonary manifestations, including ischaemic heart disease, osteoporosis, stroke and diabetes. Anxiety and depression are also common. Spirometry remains the gold standard diagnostic tool. Pharmacologic and non-pharmacologic therapy can improve symptoms, quality of life and exercise capacity and, through their effects on reducing exacerbations, have the potential to modify disease progression. Bronchodilators are the mainstay of pharmacotherapy, with guidelines recommending a stepwise escalating approach. Smoking cessation is paramount in managing COPD, with promotion of physical activity and pulmonary rehabilitation being other key factors in management. Comorbidities should be actively sought and managed in their own right. Given the chronicity and progressive nature of COPD, ongoing monitoring and support with timely discussion of advanced-care planning and end-of-life issues are recommended.

  9. 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

  10. Malignancy in coeliac disease--effect of a gluten free diet.

    PubMed

    Holmes, G K; Prior, P; Lane, M R; Pope, D; Allan, R N

    1989-03-01

    Two hundred and ten patients with coeliac disease previously reported from this unit were reviewed at the end of 1985 after a further 11 years of follow up. The initial review at the end of 1974 could not demonstrate that a gluten free diet (GFD) prevented these complications, probably because the time on diet was relatively short. The same series has therefore been kept under surveillance with the particular aim of assessing the effects of diet on malignancy after a further prolonged follow up period. Twelve new cancers have occurred: of which one was a carcinoma of the oesophagus and two lymphomas. Thirty nine cancers developed in 38 patients and of 69 deaths, 33 were the result of malignancy. A two-fold relative risk (RR) of cancer was found and was because of an increased risk of cancer of the mouth and pharynx (RR = 9.7, p less than 0.01, 95% confidence interval (CI) = 2.0-28.3), oesophagus (RR = 12.3, p less than 0.01, CI = 2.5-36.5), and of non-Hodgkin's lymphoma (RR = 42.7, p less than 0.001, CI = 19.6-81.4). The results indicate that for coeliac patients who have taken a GFD for five years or more the risk of developing cancer over all sites is not increased when compared with the general population. The risk is increased, however, in those taking a reduced gluten, or a normal diet, with an excess of cancers of the mouth, pharynx and oesophagus (RR = 22.7, p < 0.001), and also of lymphoma (RR = 77.8, p < 0.001). A significant decreasing trend in the excess morbidity rate over increasing use of a GFD was found. The results are suggestive of a protective role for a GFD against malignancy in coeliac disease and give further support for advising all patients to adhere to a strict GFD for life.

  11. Advanced interstitial chemotherapy combined with targeted treatment of malignant glioma in rats by using drug-loaded nanofibrous membranes

    PubMed Central

    Tseng, Yuan-Yun; Su, Chen-Hsing; Yang, Shun-Tai; Huang, Yin-Chen; Lee, Wei-Hwa; Wang, Yi-Chuan; Liu, Shou-Cheng; Liu, Shih-Jung

    2016-01-01

    Glioblastoma multiforme (GBM), the most prevalent and malignant form of a primary brain tumour, is resistant to chemotherapy. In this study, we concurrently loaded three chemotherapeutic agents [bis-chloroethylnitrosourea, irinotecan, and cisplatin; BIC] into 50:50 poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibres and an antiangiogenic agent (combretastatin) into 75:25 PLGA nanofibres [BIC and combretastatin (BICC)/PLGA]. The BICC/PLGA nanofibrous membranes were surgically implanted onto the brain surfaces of healthy rats for conducting pharmacodynamic studies and onto C6 glioma-bearing rats for estimating the therapeutic efficacy. The chemotherapeutic agents were rapidly released from the 50:50 PLGA nanofibres after implantation, followed by the release of combretastatin (approximately 2 weeks later) from the 75:25 PLGA nanofibres. All drug concentrations remained higher in brain tissues than in the blood for more than 8 weeks. The experimental results, including attenuated malignancy, retarded tumour growth, and prolonged survival in tumour-bearing rats, demonstrated the efficacy of the BICC/PLGA nanofibrous membranes. Furthermore, the efficacy of BIC/PLGA and BICC/PLGA nanofibrous membranes was compared. The BICC/PLGA nanofibrous membranes more efficiently retarded the tumour growth and attenuated the malignancy of C6 glioma-bearing rats. Moreover, the addition of combretastatin did not significantly change the drug release behaviour of the BIC/PLGA nanofibrous membranes. The present advanced and novel interstitial chemotherapy and targeted treatment provide a potential strategy and regimen for treating GBM. PMID:27494894

  12. The treatment of intraperitoneal malignant disease with monoclonal antibody guided 131I radiotherapy.

    PubMed Central

    Ward, B.; Mather, S.; Shepherd, J.; Crowther, M.; Hawkins, L.; Britton, K.; Slevin, M. L.

    1988-01-01

    Seven patients with small volume ovarian carcinoma, remaining after conventional therapy with surgery and a platinum containing chemotherapy regimen, were treated with intraperitoneal monoclonal antibody guided radiotherapy. 100 mCi131I conjugated to 10 mg of monoclonal antibody were injected i.p. in 2,000 ml peritoneal dialysis fluid. Patients were evaluated 3 months later; 3 had clinical progressive disease while third look laparotomy demonstrated progressive disease in 3 of the remaining 4 patients. The seventh patient did not have a third look laparotomy and is currently inevaluable for response. Five patients with recurrent malignant ascites not controlled by diuretics or repeated paracentesis were similarly treated with 75-170 mCi131I conjugated to 10 mg monoclonal antibody. In three patients the ascites was controlled for a mean of 4 months. One patient died too early to assess the control of his ascites but tumour cells disappeared from the ascitic fluid after therapy. In the patient whose ascites were not controlled, a subpopulation of antigen-negative tumour cells was demonstrated. This study was unable to demonstrate a therapeutic benefit for i.p. injected monoclonal antibody guided radiotherapy for solid intraperitoneal tumour but suggests that it may be capable of controlling the accumulation of antigen positive malignant ascites. Images Figure 1 Figure 3 Figure 4 PMID:3219277

  13. Phase I trial of arginine deprivation therapy with ADI-PEG 20 plus docetaxel in patients with advanced malignant solid tumors

    PubMed Central

    Tomlinson, Benjamin K.; Thomson, James A.; Bomalaski, John S.; Diaz, Monica; Akande, Taiwo; Mahaffey, Nichole; Li, Tianhong; Dutia, Mrinal P.; Kelly, Karen; Gong, I-Yeh; Semrad, Thomas; Gandara, David R.; Pan, Chong-Xian; Lara, Primo N.

    2015-01-01

    Purpose This phase I study examined the toxicity and tolerability, of pegylated arginine deiminase (ADI-PEG 20) in combination with docetaxel in patients with advanced solid malignancies. Experimental Design Eligible patients had histologically proven advanced solid malignancies, with any number of prior therapies, zubrod performance status 0–2 and adequate organ function. Patients received ADI-PEG 20 weekly intramuscular injection ranging from 4.5–36 mg/m2, and up to ten doses of docetaxel 75 mg/m2 every three weeks. Primary endpoints were safety, toxicity and a recommended phase II dose. Circulating arginine levels were measured prior to each cycle. Tumor response was measured as a secondary endpoint every six weeks on study. Results Eighteen patients received a total of 116 cycles of therapy through four dose levels of ADI-PEG 20. A single dose-limiting toxicity (grade 3 urticarial rash) was observed at the 1st dose level, with no additional dose-limiting toxicities observed. Hematologic toxicities were common with 14 patients experiencing at least one grade 3–4 leukopenia. Fatigue was the most prevalent toxicity reported by 16 patients. Arginine was variably suppressed with ten patients achieving at least a 50% reduction in baseline values. In 14 patients with evaluable disease, four partial responses (including two patients with PSA response) were documented and seven patients had stable disease. Conclusions ADI-PEG 20 demonstrated reasonable toxicity in combination with docetaxel. Promising clinical activity was noted and expansion cohorts are now accruing for both castrate resistant prostate cancer and non-small cell lung cancer at a recommended phase II dose of 36 mg/m2. PMID:25739672

  14. A first-in-human, phase 1, dose-escalation study of dinaciclib, a novel cyclin-dependent kinase inhibitor, administered weekly in subjects with advanced malignancies

    PubMed Central

    2013-01-01

    Background Dinaciclib, a small-molecule, cyclin-dependent kinase inhibitor, inhibits cell cycle progression and proliferation in various tumor cell lines in vitro. We conducted an open-label, dose-escalation study to determine the safety, tolerability, and bioactivity of dinaciclib in adults with advanced malignancies. Methods Dinaciclib was administered starting at a dose of 0.33 mg/m2, as a 2-hour intravenous infusion once weekly for 3 weeks (on days 1, 8, and 15 of a 28-day cycle), to determine the maximum administered dose (MAD), dose-limiting toxicities (DLTs), recommended phase 2 dose (RP2D), and safety and tolerability. Pharmacodynamics of dinaciclib were assessed using an ex vivo phytohemagglutinin lymphocyte stimulation assay and immunohistochemistry staining for retinoblastoma protein phosphorylation in skin biopsies. Evidence of antitumor activity was assessed by sequential computed tomography imaging after every 2 treatment cycles. Results Forty-eight subjects with solid tumors were treated. The MAD was found to be 14 mg/m2 and the RP2D was determined to be 12 mg/m2; DLTs at the MAD included orthostatic hypotension and elevated uric acid. Forty-seven (98%) subjects reported adverse events (AEs) across all dose levels; the most common AEs were nausea, anemia, decreased appetite, and fatigue. Dinaciclib administered at the RP2D significantly inhibited lymphocyte proliferation, demonstrating a pharmacodynamic effect. Ten subjects treated at a variety of doses achieved prolonged stable disease for at least 4 treatment cycles. Conclusions Dinaciclib administered every week for 3 weeks (on days 1, 8, and 15 of a 28-day cycle) was generally safe and well tolerated. Initial bioactivity and observed disease stabilization support further evaluation of dinaciclib as a treatment option for patients with advanced solid malignancies. Trial registration ClinicalTrials.gov # NCT00871663 PMID:24131779

  15. A phase I trial of chlorambucil administered in short pulses in patients with advanced malignancies.

    PubMed

    Blumenreich, M S; Woodcock, T M; Sherrill, E J; Richman, S P; Gentile, P S; Epremian, B E; Kubota, T T; Allegra, J C

    1988-01-01

    We carried out a phase I trial with chlorambucil. Thirty patients with advanced cancer were entered in six dose levels: 36, 48, 60, 84, 108, and 144 mg/m2. The drug was given in six divided oral doses every 6 hours and the regimen was repeated every 3 weeks. The median age was 62 years (31-84), median Karnofsky performance status (KPS) 60 (40-90). All patients but one had received prior radiation therapy, chemotherapy, or both. Central nervous system toxicity was dose limiting, occurring in 5 of 6 patients at 144 mg/m2. It was characterized by transient seizures, hallucinations, lethargy, stupor, and coma. Metoclopramide was successful in controlling nausea and vomiting, which was severe if the antiemetic was not used. Leukopenia (3 patients) and thrombocytopenia (2 patients) were mild. One patient with colorectal carcinoma had a minor response, and two patients with non-small cell lung cancer had stable disease. A safe dose for phase II trials is 108 mg/m2 in six 6-hourly oral doses.

  16. Phase I study of tanespimycin in combination with bortezomib in patients with advanced solid malignancies

    PubMed Central

    Schenk, Erin; Wahner Hendrickson, Andrea E.; Northfelt, Donald; Toft, David O.; Ames, Matthew M.; Menefee, Michael; Satele, Daniel; Qin, Rui; Erlichman, Charles

    2014-01-01

    Summary Purpose To determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLT) of tanespimycin when given in combination with bortezomib. Experimental design Phase I dose-escalating trial using a standard cohort “3+3” design performed in patients with advanced solid tumors. Patients were given tanespimycin and bortezomib twice weekly for 2 weeks in a 3 week cycle (days 1, 4, 8, 11 every 21 days). Results Seventeen patients were enrolled in this study, fifteen were evaluable for toxicity, and nine patients were evaluable for tumor response. The MTD was 250 mg/m2 of tanespimycin and 1.0 mg/m2 of bortezomib when used in combination. DLTs of abdominal pain (13%), complete atrioventricular block (7%), fatigue (7%), encephalopathy (7%), anorexia (7%), hyponatremia (7%), hypoxia (7%), and acidosis (7%) were observed. There were no objective responses. One patient had stable disease. Conclusions The recommended phase II dose for twice weekly 17-AAG and PS341 are 250 mg/m2 and 1.0 mg/m2respectively, on days 1, 4, 8 and 11 of a 21 day cycle. PMID:23543109

  17. Isolated testicular immunoglobulin G4-related disease: A mimicker of malignancy

    PubMed Central

    Lal, Jithin; Bhat, Suresh; Doddamani, Siddalingeswar; Devi, Lekshmi

    2016-01-01

    ImmunoglobulinG4 related disease (IgG4RD) is a systemic fibroinflammatory disease recognized recently. This usually presents with multiorgan involvement. We are reporting a case of a35-year-old male patient with isolated IgG4RD of the testis. This patient presented with right testis pain which responded to conservative treatment. However, later, he reported with hard swelling in the right testis which on imaging was suggestive of malignancy and hence underwent radical orchiectomy. Histopathology with immunohistochemical staining confirmed IgG4RD of the testis. To the best of our knowledge, this is the first report of purely isolated case of IgG4RD of testis in English literature. PMID:27843221

  18. A case of Mikulicz's disease complicated by malignant lymphoma: a postmortem histopathological finding.

    PubMed

    Uehara, Takeshi; Ikeda, Shu-ichi; Hamano, Hideaki; Kawa, Shigeyuki; Moteki, Hideaki; Matsuda, Kazuyuki; Kaneko, Yasunori; Hara, Eiji

    2012-01-01

    A 66-year-old Japanese man with an 11-year history of Mikulicz's disease (MD) received continuous corticosteroid administration. At age 58, a left renal pelvic mass was identified and diagnosed as an IgG4-related inflammatory pseudotumor. The patient underwent an operation to remove the tumor. Subsequently, he contracted repeated pulmonary infections and eventually died of severe gastrointestinal bleeding. Autopsy revealed systemic lymph node swelling and infiltration in some organs, and diffuse large B-cell lymphoma (DLBCL) was diagnosed. These findings suggest that an IgG4-related disease can be causally related to the development of malignant lymphoma through the occurrence of mucosa-associated lymphoid tissue lymphoma.

  19. Tasmanian devil facial tumor disease: insights into reduced tumor surveillance from an unusual malignancy.

    PubMed

    O'Neill, Iain D

    2010-10-01

    Tasmanian devil facial tumor disease (DFTD) is a highly aggressive cancer involving the facial tissues that currently presents a serious extinction risk for the Tasmanian devil population. Although the histogenesis is uncertain, an origin from a neural crest cell-lineage is considered likely. Epidemiological, cytogenetic and immunological data all support the premise that DFTD arose from a single tumor clone from an individual diseased animal, and is being transmitted between individual animals as a tumor "allograft" by biting during social interaction. The spread of this cancer throughout the species is believed to be facilitated by a reduced MHC diversity, possibly as a result of an evolutionary bottleneck. The pathogenesis of DFTD has some similarities with certain human cancers, including donor-recipient tumor transmission, which may complicate organ transplantation, and certain forms of malignancy at the maternal/fetal interface. The natural history and pathology of DFTD, and the data describing this highly unusual tumor biology are discussed.

  20. Non-malignant respiratory diseases and occupational exposure to wood dust. Part II. Dry wood industry.

    PubMed

    Jacobsen, Gitte; Schaumburg, Inger; Sigsgaard, Torben; Schlunssen, Vivi

    2010-01-01

    This paper reviews the literature on associations between dry wood dust exposure and non-malignant respiratory diseases. Criteria for inclusion are epidemiological studies in English language journals with an internal or external control group describing relationships between dry wood dust exposure and respiratory diseases or symptoms. Papers took into consideration smoking and when dealing with lung function age. A total of 37 papers forms the basis of this review. The results support an association between dry wood dust exposure and asthma, asthma symptoms, coughing, bronchitis, and acute and chronic impairment of lung function. In addition, an association between wood dust exposure and rhino-conjunctivitis is seen across the studies. Apart from plicatic acid in western red cedar wood, no causal agent has consistently been disclosed. Type 1 allergy is not suspected to be a major cause of wood dust induced asthma.

  1. 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

  2. B Lymphocytes in Untreated Patients with Malignant Lymphoma and Hodgkin's Disease

    PubMed Central

    Gajl-Peczalska, Kazimiera J.; Hansen, John A.; Bloomfield, Clara D.; Good, Robert A.

    1973-01-01

    B and T lymphocytes in 37 untreated patients with malignant lymphoma and Hodgkin's disease were studied. B cells in the peripheral blood were investigated with respect to surface immunoglobulins and in a few patients with respect to intracytoplasmic immunoglobulins by means of immunofluorescence. T cell function was studied by direct phytohemagglutinin (PHA) microtest (from the same sample of whole blood), mixed lymphocyte culture (MLC), and by delayed hypersensitivity to various antigens. In the 13 patients with Hodgkin's disease the histologic subtype was nodular sclerosis in nine, lymphocyte predominant in two, mixed cellularity in two. Only one of these patients had disseminated disease (stage IV); he showed impaired cellular immunity, a very low percentage of B cells and low levels of serum immunoglobulins. Of the remaining patients with Hodgkin's disease, with one exception, normal percentages but rather low absolute numbers of B lymphocytes per mm3 of blood were found. One patient with a low percent and low absolute number of B lymphocytes showed very high serum IgG. Of 24 patients with non-Hodgkin's malignant lymphoma, seven (29%) showed monoclonal B cell proliferation in the peripheral blood (five μκ, two γκ). By morphologic criteria, 14 patients had involvement of bone marrow, five of these had involvement of peripheral blood. Four of the latter five patients showed marked increases in percentages and absolute numbers of B lymphocytes in the peripheral blood reflecting the monoclonal proliferation. In three additional patients monoclonal proliferation of lymphocytes was found by immunofluorescence although the blood smears appeared morphologically normal. Serum immunoglobulin abnormalities without monoclonal B cell proliferation in the peripheral blood were observed in six patients. Images PMID:4201499

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

    PubMed

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

    2015-12-01

    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.

  4. 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

  5. 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

  6. Tomographic imaging of the spleen: the role of morphological and metabolic features in differentiating benign from malignant diseases.

    PubMed

    Mainenti, Pier Paolo; Iodice, Delfina; Cozzolino, Immacolata; Segreto, Sabrina; Capece, Sergio; Sica, Giacomo; Magliulo, Mario; Ciancia, Giuseppe; Pace, Leonardo; Salvatore, Marco

    2012-01-01

    To evaluate the tomographic features in differentiating benign from malignant splenic diseases, 54 patients with a cytohistological examination and a contrast-enhanced multidetector computed tomography (ce-MDCT) and/or positron emission tomography/computed tomography (PET/CT) were retrospectively selected. Significant associations were observed between ce-MDCT Pattern 3 (focal hyperdense lesion) and Pattern 4 (infarcts/cysts) as well as PET/CT Pattern 3 (focal photopenia/diffuse uptakemalignant diseases. No significant association between benign or malignant diseases and spleen volumes and maximum standardized uptake value (SUV(max)) as well as lesion characteristics was observed. The metabolic data do not improve the performance of morphological patterns.

  7. 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

  8. Opportunities and limitations of natural killer cells as adoptive therapy for malignant disease.

    PubMed

    Davies, James O J; Stringaris, Kate; Barrett, A John; Rezvani, Katayoun

    2014-11-01

    Although natural killer (NK) cells can be readily generated for adoptive therapy with current techniques, their optimal application to treat malignant diseases requires an appreciation of the dynamic balance between signals that either synergize with or antagonize each other. Individuals display wide differences in NK function that determine their therapeutic efficacy. The ability of NK cells to kill target cells or produce cytokines depends on the balance between signals from activating and inhibitory cell-surface receptors. The selection of NK cells with a predominant activating profile is critical for delivering successful anti-tumor activity. This can be achieved through selection of killer immunoglobulin-like receptor-mismatched NK donors and by use of blocking molecules against inhibitory pathways. Optimum NK cytotoxicity may require licensing or priming with tumor cells. Recent discoveries in the molecular and cellular biology of NK cells inform in the design of new strategies, including adjuvant therapies, to maximize the cytotoxic potential of NK cells for adoptive transfer to treat human malignancies.

  9. Carbon ion therapy for advanced sinonasal malignancies: feasibility and acute toxicity

    PubMed Central

    2011-01-01

    Purpose To evaluate feasibility and toxicity of carbon ion therapy for treatment of sinonasal malignancies. First site of treatment failure in malignant tumours of the paranasal sinuses and nasal cavity is mostly in-field, local control hence calls for dose escalation which has so far been hampered by accompanying acute and late toxicity. Raster-scanned carbon ion therapy offers the advantage of sharp dose gradients promising increased dose application without increase of side-effects. Methods Twenty-nine patients with various sinonasal malignancies were treated from 11/2009 to 08/2010. Accompanying toxicity was evaluated according to CTCAE v.4.0. Tumor response was assessed according to RECIST. Results Seventeen patients received treatment as definitive RT, 9 for local relapse, 2 for re-irradiation. All patients had T4 tumours (median CTV1 129.5 cc, CTV2 395.8 cc), mostly originating from the maxillary sinus. Median dose was 73 GyE mostly in mixed beam technique as IMRT plus carbon ion boost. Median follow- up was 5.1 months [range: 2.4 - 10.1 months]. There were 7 cases with grade 3 toxicity (mucositis, dysphagia) but no other higher grade acute reactions; 6 patients developed grade 2 conjunctivits, no case of early visual impairment. Apart from alterations of taste, all symptoms had resolved at 8 weeks post RT. Overall radiological response rate was 50% (CR and PR). Conclusion Carbon ion therapy is feasible; despite high doses, acute reactions were not increased and generally resolved within 8 weeks post radiotherapy. Treatment response is encouraging though follow-up is too short to estimate control rates or evaluate potential late effects. Controlled trials are warranted. PMID:21466696

  10. Advanced imaging in valvular heart disease.

    PubMed

    Bax, Jeroen J; Delgado, Victoria

    2017-04-01

    Although echocardiography remains the mainstay imaging technique for the evaluation of patients with valvular heart disease (VHD), innovations in noninvasive imaging in the past few years have provided new insights into the pathophysiology and quantification of VHD, early detection of left ventricular (LV) dysfunction, and advanced prognostic assessment. The severity grading of valve dysfunction has been refined with the use of Doppler echocardiography, cardiac magnetic resonance (CMR), and CT imaging. LV ejection fraction remains an important criterion when deciding whether patients should be referred for surgery. However, echocardiographic strain imaging can now detect impaired LV systolic function before LV ejection fraction reduces, thus provoking the debate on whether patients with severe VHD should be referred for surgery at an earlier stage (before symptom onset). Impaired LV strain correlates with the amount of myocardial fibrosis detected with CMR techniques. Furthermore, accumulating data show that the extent of fibrosis associated with severe VHD has important prognostic implications. The present Review focuses on using these novel imaging modalities to assess pathophysiology, early LV dysfunction, and prognosis of major VHDs, including aortic stenosis, mitral regurgitation, and aortic regurgitation.

  11. Biomarkers in Parkinson's disease: Advances and strategies.

    PubMed

    Delenclos, Marion; Jones, Daryl R; McLean, Pamela J; Uitti, Ryan J

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor disturbances and affects more than 1% of the worldwide population. Despite considerable progress in understanding PD pathophysiology, including genetic and biochemical causes, diagnostic approaches lack accuracy and interventions are restricted to symptomatic treatments. PD is a complex syndrome with different clinical subtypes and a wide variability in disorder course. In order to deliver better clinical management of PD patients and discovery of novel therapies, there is an urgent need to find sensitive, specific, and reliable biomarkers. The development of biomarkers will not only help the scientific community to identify populations at risk, but also facilitate clinical diagnosis. Furthermore, these tools could monitor progression, which could ultimately deliver personalized therapeutic strategies. The field of biomarker discovery in PD has attracted significant attention and there have been numerous contributions in recent years. Although none of the parameters have been validated for clinical practice, some candidates hold promise. This review summarizes recent advances in the development of PD biomarkers and discusses new strategies for their utilization.

  12. Biomarkers in Parkinson's disease: Advances and strategies

    PubMed Central

    Delenclos, Marion; Jones, Daryl R.; McLean, Pamela J.; Uitti, Ryan J.

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor disturbances and affects more than 1% of the worldwide population. Despite considerable progress in understanding PD pathophysiology, including genetic and biochemical causes, diagnostic approaches lack accuracy and interventions are restricted to symptomatic treatments. PD is a complex syndrome with different clinical subtypes and a wide variability in disorder course. In order to deliver better clinical management of PD patients and discovery of novel therapies, there is an urgent need to find sensitive, specific, and reliable biomarkers. The development of biomarkers will not only help the scientific community to identify populations at risk, but also facilitate clinical diagnosis. Furthermore, these tools could monitor progression, which could ultimately deliver personalized therapeutic strategies. The field of biomarker discovery in PD has attracted significant attention and there have been numerous contributions in recent years. Although none of the parameters have been validated for clinical practice, some candidates hold promise. This review summarizes recent advances in the development of PD biomarkers and discusses new strategies for their utilization. PMID:26439946

  13. Stereotactic Ablative Radiosurgery for Locally Advanced or Recurrent Skull Base Malignancies with Prior External Beam Radiation Therapy

    PubMed Central

    Xu, Karen M.; Quan, Kimmen; Clump, David A.; Ferris, Robert L.; Heron, Dwight E.

    2015-01-01

    Purpose: Stereotactic ablative radiotherapy (SABR) is an attractive modality to treat malignancies invading the skull base as it can deliver a highly conformal dose with minimal toxicity. However, variation exists in the prescribed dose and fractionation. The purpose of our study is to examine the local control, survival, and toxicities in SABR for the treatment of previously irradiated malignant skull base tumors. Materials and methods: A total of 31 patients and 40 locally advanced or recurrent head and neck malignancies involving the skull base treated with a common SABR regimen, which delivers a radiation dose of 44 Gy in 5 fractions from January 1st, 2004 to December 31st, 2013, were retrospectively reviewed. The local control rate (LC), progression-free survival rate, overall survival (OS) rate, and toxicities were reported. Results: The median follow-up time of all patients was 11.4 months (range: 0.6–67.2 months). The median tumor volume was 27 cm3 (range: 2.4–205 cm3). All patients received prior external beam radiation therapy with a median radiation dose of 64 Gy (range: 24–75.6 Gy) delivered in 12–42 fractions. Twenty patients had surgeries prior to SABR. Nineteen patients received chemotherapy. Specifically, eight patients received concurrent cetuximab (Erbitux™) with SABR. The median time-to-progression (TTP) was 3.3 months (range: 0–16.9 months). For the 29 patients (93.5%) who died, the median time from the end of first SABR to death was 10.3 months (range: 0.5–41.4 months). The estimated 1-year OS rate was 35%. The estimated 2-year OS rate was 12%. Treatment was well-tolerated without grade 4 or 5 treatment-related toxicities. Conclusion: Stereotactic ablative radiotherapy has been shown to achieve low toxicities in locally advanced or recurrent, previously irradiated head and neck malignancies invading the skull base. PMID:25853093

  14. 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

  15. [Advantages and disadvantages in the use of central venous catheters in children with malignant diseases].

    PubMed

    Sporisević, L; Hasanbegović, E; Hadzihasanović, E; Bajraktarević, A; Khatib, H; Hamamdzić, M

    1999-01-01

    The authors report the problem of central venous catheter appliance to the children with malignant diseases, employed for the first time in Bosnia and Herzegovina with the aim of pediatric oncologic patients treatment. During 1997 central venous catheter type Hickman was used in nine children between two and half to eleven years old (average six years and one months). The average time of catheter placement was six months, in two cases catheter were eliminated after two and three months respectively since application (spontaneous elimination and repeated septic attacks, caused bu resistant bacterial strains). Gram-positive bacteria have been isolated with eight children (Staphylococcus aureus and Staphylococcus epidermidis), and gram-negative enterobacteriaceae (Serratia marcescens, Pseudomonas aeruginosa, Klebsiella oxytocia and pneumoniae, Escherichia coli, Salmonella group C and Enterococcus faecalis) in samples taken from the catheter and hemoculture. The central venous catheter is useful in treating oncological patients, but may cause serious consequences, like local infections or septicaemia.

  16. Dermoscopic Features of Pigmented Bowen's Disease in a Japanese Female Mimicking Malignant Melanoma

    PubMed Central

    Inoue, Takayuki; Kobayashi, Ken; Sawada, Mizuki; Ishizaki, Sumiko; Ito, Haruo; Fujibayashi, Mariko; Tanaka, Masaru

    2010-01-01

    Various structures have been reported for dermoscopic features of pigmented Bowen's disease (BD), which could be a mimic of various pigmented skin lesions. A 79-year-old Japanese woman presented with a 3-year history of brown-black macule on her right upper arm without symptom. Dermoscopic examination demonstrated irregular flossy streaks, irregular brown dots/globules, blue-whitish regression structures, and overlaying whitish scaly areas. We suspected pigmented skin lesions including seborrheic keratosis, pigmented eccrine poroma, and malignant melanoma and excised completely with a 5 mm margin. Histopathological features were consistent with a diagnosis of pigmented BD. Although similar dermoscopic features might be revealed in pigmented skin lesions and it may occasionally be difficult to distinguish between pigmented BD and other pigmented skin lesions, dermoscopy would be useful in speculating pathologic features of pigmented BD. PMID:20811602

  17. Recent advances in echocardiography for valvular heart disease.

    PubMed

    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.

  18. 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

  19. CREST biorepository for translational studies on malignant mesothelioma, lung cancer and other respiratory tract diseases: Informatics infrastructure and standardized annotation

    PubMed Central

    UGOLINI, DONATELLA; NERI, MONICA; BENNATI, LUCA; CANESSA, PIER ALDO; CASANOVA, GEORGIA; LANDO, CECILIA; LEONCINI, GIACOMO; MARRONI, PAOLA; PARODI, BARBARA; SIMONASSI, CLAUDIO; BONASSI, STEFANO

    2012-01-01

    Advances in molecular epidemiology and translational research have led to the need for biospecimen collection. The Cancer of the Respiratory Tract (CREST) biorepository is concerned with pleural malignant mesothelioma (MM) and lung cancer (LC). The biorepository staff has collected demographic and epidemiological data directly from consenting subjects using a structured questionnaire, in agreement with The Public Population Project in Genomics (P3G). Clinical and follow-up data were collected. Sample data were also recorded. The architecture is based on a database designed with Microsoft Access. Data standardization was carried out to conform with established conventions or procedures. As from January 31, 2011, the overall number of recruited subjects was 1,857 (454 LC, 245 MM, 130 other cancers and 1,028 controls). Due to its infrastructure, CREST was able to join international projects, sharing samples and/or data with other research groups in the field. The data management system allows CREST to be involved, through a minimum data set, in the national project for the construction of the Italian network of Oncologic BioBanks (RIBBO), and in the infrastructure of a pan-European biobank network (BBMRI). The CREST biorepository is a valuable tool for translational studies on respiratory tract diseases, because of its simple and efficient infrastructure. PMID:22969926

  20. 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

  1. 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.

  2. [High dose cinobufocini in attenuation and treatment of infection and granulocytopenia during combined chemotherapy of malignant blood diseases].

    PubMed

    Yue, B B

    1992-03-01

    The use of high dose Cinobufocini in attenuation and treatment of infection and granulocytopenia during combined chemotherapy was observed in patients with malignant blood diseases. The study was designed in such a way that each patient served as self control. The patients, 18 males and 12 females, aged 16-66 (average 34), 62 experiments in 20 patients with acute leukemia, 8 with malignant lymphoma and 2 with multiple myeloma were observed. In patients with the treatment of high dose Cinobufocini, infection was significantly decreased and the number of granulocytes was not markedly changed before and after the treatment. The observation demonstrated that high dose Cinobufocini can significantly reduce the risk of infection and degree and duration of granulocytopenia associated with chemotherapy of patients with malignant blood diseases. The use of high dose Cinobufocini is simple and convenient and with very little side effects.

  3. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma.

    PubMed

    Van Meir, Erwin G; Hadjipanayis, Costas G; Norden, Andrew D; Shu, Hui-Kuo; Wen, Patrick Y; Olson, Jeffrey J

    2010-01-01

    Malignant gliomas are the most common and deadly brain tumors. Nevertheless, survival for patients with glioblastoma, the most aggressive glioma, although individually variable, has improved from an average of 10 months to 14 months after diagnosis in the last 5 years due to improvements in the standard of care. Radiotherapy has been of key importance to the treatment of these lesions for decades, and the ability to focus the beam and tailor it to the irregular contours of brain tumors and minimize the dose to nearby critical structures with intensity-modulated or image-guided techniques has improved greatly. Temozolomide, an alkylating agent with simple oral administration and a favorable toxicity profile, is used in conjunction with and after radiotherapy. Newer surgical techniques, such as fluorescence-guided resection and neuroendoscopic approaches, have become important in the management of malignant gliomas. Furthermore, new discoveries are being made in basic and translational research, which are likely to improve this situation further in the next 10 years. These include agents that block 1 or more of the disordered tumor proliferation signaling pathways, and that overcome resistance to already existing treatments. Targeted therapies such as antiangiogenic therapy with antivascular endothelial growth factor antibodies (bevacizumab) are finding their way into clinical practice. Large-scale research efforts are ongoing to provide a comprehensive understanding of all the genetic alterations and gene expression changes underlying glioma formation. These have already refined the classification of glioblastoma into 4 distinct molecular entities that may lead to different treatment regimens. The role of cancer stem-like cells is another area of active investigation. There is definite hope that by 2020, new cocktails of drugs will be available to target the key molecular pathways involved in gliomas and reduce their mortality and morbidity, a positive development

  4. 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.

  5. Advances in environmental and occupational respiratory diseases in 2009.

    PubMed

    Peden, David B; Bush, Robert K

    2010-03-01

    The year 2009 led to a number of significant advances in environmental and occupational allergic diseases. The role of exposure to environmental pollutants, respiratory viruses, and allergen exposure showed significant advances. New allergens were identified. Occupational asthma and the relationship of complementary and alternative medicine to allergic diseases were extensively reviewed. New approaches to immunotherapy, novel vaccine techniques, and methods to reduce risks for severe allergic disease were addressed.

  6. Endothelial cell colony forming units derived from malignant breast diseases are resistant to tumor necrosis factor-α-induced apoptosis.

    PubMed

    Chou, Chen-Pin; Jiang, Shih Sheng; Pan, Huay-Ben; Yen, Yi-Chen; Tseng, Hui-Hwa; Hung, Yu-Ting; Wang, Ssu-Han; Chen, Yu-Lin; Chen, Ya-Wen

    2016-11-24

    Mobilisation of endothelial progenitor cells (EPCs) from the bone marrow is a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be elevated in certain malignant states. Using flow cytometry and a Hill-based colony forming unit (CFU) assay, the present study indicated that higher levels of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2) double-positive EPCs, as well as increased formation of endothelial cell colony-forming units (EC-CFUs) are associated with benign and malignant breast diseases, providing possible indicators for breast disease detection. Gene expression profiles revealed a genetic difference between CD34(+) VEGFR2(+) EPCs and EC-CFUs. Decreased expression of tumour necrosis factor receptor 2 (TNFR2) signalling-related genes and inhibition of tumour necrosis factor (TNF)-induced signalling were demonstrated in EC-CFUs derived from patients with malignant breast disease in comparison with those from healthy controls. Interestingly, our data provided the first evidence that EC-CFUs derived from patients with malignant breast disease were resistant to TNF-α-induced apoptosis, indicating a plausible target for future therapeutic interventions.

  7. Endothelial cell colony forming units derived from malignant breast diseases are resistant to tumor necrosis factor-α-induced apoptosis

    PubMed Central

    Chou, Chen-Pin; Jiang, Shih Sheng; Pan, Huay-Ben; Yen, Yi-Chen; Tseng, Hui-Hwa; Hung, Yu-Ting; Wang, Ssu-Han; Chen, Yu-Lin; Chen, Ya-Wen

    2016-01-01

    Mobilisation of endothelial progenitor cells (EPCs) from the bone marrow is a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be elevated in certain malignant states. Using flow cytometry and a Hill-based colony forming unit (CFU) assay, the present study indicated that higher levels of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2) double-positive EPCs, as well as increased formation of endothelial cell colony-forming units (EC-CFUs) are associated with benign and malignant breast diseases, providing possible indicators for breast disease detection. Gene expression profiles revealed a genetic difference between CD34+ VEGFR2+ EPCs and EC-CFUs. Decreased expression of tumour necrosis factor receptor 2 (TNFR2) signalling-related genes and inhibition of tumour necrosis factor (TNF)-induced signalling were demonstrated in EC-CFUs derived from patients with malignant breast disease in comparison with those from healthy controls. Interestingly, our data provided the first evidence that EC-CFUs derived from patients with malignant breast disease were resistant to TNF-α-induced apoptosis, indicating a plausible target for future therapeutic interventions. PMID:27881867

  8. 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.

  9. Successful Advance Directives through Quality Disease Management.

    PubMed

    Parke, Bob; Krajewski, Adam

    2010-01-01

    Recently there has been talk about the benefit of advance care planning. This is an issue which resurfaces from time to time, as is evident in recent New England Journal of Medicine articles and editorials (April 2010). It has also resurfaced in Canada in a recent document titled Advance Care Planning in Canada: National Framework for Consultation (Health Canada 2010). This document acknowledges that many of us believe in the value of advance directives, finding "that most of the general public (60-90%) is supportive of advance care planning. However, only 10-20% of the public in the US, Canada and Australia have completed an advance care plan of any kind" (Health Canada 2010: 6). In Muriel R. Gillick's editorial in the New England Journal Medicine, she strongly makes the point that few people complete advance directives and further states that "directives have been a resounding failure" (Gillick 2010: 1239). These statements, although not exhaustive on the subject, show that we have a problem translating the support for advance directives into actual plans.

  10. [IgG4-related disease is a rare differential diagnosis of malignant and autoimmune diseases].

    PubMed

    Storgaard, Anders; Detlefsen, Sönke

    2015-04-06

    Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory and fibrotic disease with the potential to produce diffuse enlargement, massforming lesions or stenoses in a wide range of organs. Elevation of serum IgG4 concentration and high levels of IgG4-positive cells in the inflamed tissue are common denominators. Type 1 autoimmune pancreatitis is one of the main manifestations, and its recognition preceded the definition of IgG4-RD as a novel clinical entity. The aetiology, pathophysiology, epidemiology and clinical long-term outcome of IgG4-RD are not fully elucidated. Steroids are effective in most patients, sometimes combined with other antiinflammatory drugs.

  11. Malignant mesothelioma: Canadian perspective and research directions

    PubMed Central

    Lee, C.W.; Martin, J.; MacRae, R.; Tsao, M.S.; Nguyen, E.; Johnston, M.; Baas, P.; Laurie, S.; Feld, R.; Murray, N.; Shepherd, F.A.

    2008-01-01

    Since the 1960s, the incidence of malignant mesothelioma in Canada has increased dramatically because of work-related asbestos exposures. Treatment options are limited. Although chemotherapy is now an accepted standard in the management of advanced disease, uncertainty surrounds the roles of radical surgery and radiation. In March 2007, a symposium was held in Vancouver, B.C., to review the current approach to malignant mesothelioma in Canada and to discuss development of a national clinical research strategy.

  12. Photodynamic therapy--1994: treatment of benign and malignant upper aerodigestive tract disease

    NASA Astrophysics Data System (ADS)

    Schweitzer, Vanessa G.

    1995-03-01

    From 1983 to 1994 Phase II and III clinical studies at Henry Ford Hospital demonstrated complete or partial responses in 46 of 47 patients treated with hematoporphyrin-derivative photodynamic therapy (HPD-PDT) for a variety of benign and malignant upper aerodigestive tract disease: (1) superficial `condemned mucosa' or `field cancerization' of the oral cavity; (2) stage III/IV head and neck cancer; (3) mucocutaneous AIDS-related Kaposi's sarcoma of the upper aerodigestive tract; (4) recurrent laryngotracheal papillomatosis; (5) severe dysplasia/adenocarcinoma in situ in Barrett's esophagus; (6) partial or completely obstructing terminal esophageal cancer. HPD-PDT produced complete responses in 19 patients (follow up 6 months to 8 years) with `field cancerization' (CIS, T1) of the oral cavity and larynx (6), adenocarcinoma in situ in Barrett's esophagus (2), mucocutaneous Kaposi's sarcoma (9), obstructing esophageal carcinoma (1), and stage IV squamous cell carcinoma of the nasopharynx (1). PDT treatment protocols, results, complications, and application as adjunct or primary oncologic therapy for head and neck disease are reviewed.

  13. IgG4-related mastitis, a rare disease, can radiologically and histologically mimic malignancy.

    PubMed

    Yamada, Rin; Horiguchi, Shin-ichiro; Yamashita, Toshinari; Kamisawa, Terumi

    2016-03-23

    IgG4-related disease (IgG4-RD) is characterised by high serum concentrations of IgG4, dense lymphoplasmacytic infiltrates, storiform fibrosis and increased IgG4-positive plasma cells in tissues. This systemic disease occurs in various organs metachronously, but IgG4-related mastitis appears extremely rare. We report a case of IgG4-related mastitis, radiologically considered to represent breast cancer mainly composed of intraductal component and requiring histological differentiation from mucosa-associated lymphoid tissue (MALT) lymphoma. The breast mass disappeared with steroid therapy. When patients have a breast mass, regardless of the presence or absence of IgG4-RD, IgG4-related mastitis should be considered in addition to breast cancer. If histological findings show dense lymphoplasmacytic infiltrates, IgG4-related mastitis should be suspected in addition to malignant lymphoma, and lack of monoclonality should be confirmed. To avoid unnecessary surgery or chemotherapy, knowledge and accurate diagnosis of the entity of IgG4-related mastitis is necessary.

  14. Role of HERG1 potassium channel in both malignant transformation and disease progression in head and neck carcinomas.

    PubMed

    Menéndez, Sofía T; Rodrigo, Juan P; Alvarez-Teijeiro, Saúl; Villaronga, M Ángeles; Allonca, Eva; Vallina, Aitana; Astudillo, Aurora; Barros, Francisco; Suárez, Carlos; García-Pedrero, Juana M

    2012-08-01

    Evidence indicates that human ether à-go-go-related gene 1 (HERG1) voltage-gated potassium channels could represent new valuable membrane therapeutic targets and diagnostic/prognostic biomarkers in various cancers. This study is the first to investigate the expression pattern of HERG1 potassium channel subunit in both primary tumors and precancerous lesions to establish its clinical and biological role during the development and progression of head and neck squamous cell carcinomas. HERG1 protein expression was evaluated by immunohistochemistry in paraffin-embedded tissue specimens from 133 patients with laryngeal/hypopharyngeal squamous cell carcinomas and 75 patients with laryngeal dysplasia, and correlated with clinical data. Our findings demonstrate that HERG1 is frequently aberrantly expressed in a high percentage of primary tumors (87%), whereas expression was negligible in both stromal cells and normal-adjacent epithelia. HERG1 expression increased during head and neck squamous cell carcinoma progression and was significantly associated with lymph node metastasis (P=0.04), advanced disease stages (P<0.001), regional tumor recurrence (P=0.004), distant metastasis (P=0.03) and reduced disease-specific survival (P=0.012, log-rank test). HERG1-positive expression was also detected in 31 (41%) of 75 laryngeal dysplasias. Interestingly, HERG1 expression increased with the grade of dysplasia; however, HERG1 expression but not histology correlated significantly with increased laryngeal cancer risk (P=0.007). In addition, functional studies in head and neck squamous cell carcinoma-derived cell lines further revealed that HERG1 expression promotes anchorage-dependent and -independent cell growth and invasive capability, although independently of its ion-conducting function. Our data demonstrate that HERG1 expression is a biologically and clinically relevant feature in head and neck squamous cell carcinoma progression and also during malignant transformation, and a

  15. Thiopurines related malignancies in inflammatory bowel disease: Local experience in Granada, Spain

    PubMed Central

    Gómez-García, María; Cabello-Tapia, Maria José; Sánchez-Capilla, Antonio Damián; De Teresa-Galván, Javier; Redondo-Cerezo, Eduardo

    2013-01-01

    AIM: To investigate the incidence of neoplasms in inflammatory bowel disease (IBD) patients and the potential causative role of thiopurines. METHODS: We performed an observational descriptive study comparing the incidence of malignancies in IBD patients treated with thiopurines and patients not treated with these drugs. We included 812 patients which were divided in two groups depending on whether they have received thiopurines or not. We have studied basal characteristics of both groups (age when the disease was diagnosed, sex, type of IBD, etc.) and treatments received (Azathioprine, mercaptopurine, infliximab, adalimumab or other immunomodulators), as well as neoplasms incidence. Univariate analysis was performed with the student t test, χ2 test or Wilcoxon exact test as appropriate. A logistic regression analysis was performed as multivariate analysis. Statistical significance was establish at P values of less than 0.05, and 95%CI were used for the odds ratios. RESULTS: Among 812 patients included, 429 (52.83%) have received thiopurines: 79.5% azathioprine, 14% mercaptopurine and 6.5% both drugs. 44.76% of patients treated with thiopurines and 46, 48% of patients who did not receive this treatment were women (P > 0.05). The proportion of ulcerative colitis patients treated with thiopurines was 30.3% compare to 66. 67% of patients not treated (P < 0.001). Mean azathioprine dose was 123.79 ± 36.5 mg/d (range: 50-250 mg/d), mean usage time was 72.16 ± 55.7 mo (range: 1-300 mo) and the accumulated dose along this time was 274.32 ± 233.5 g (1.5-1350 g). With respect to mercaptopurine, mean dose was 74.7 ± 23.9 mg/d (range: 25-150 mg/d), mean usage time of 23.37 ± 27.6 mo (range: 1-118 mo), and the accumulated dose along this time was 52.2 ± 63.5 g (range: 1.5-243 g). Thiopurine S-methyltransferase activity was tested in 66% of patients treated with thiopurines, among which 98.2% had an intermediate or high activity. Among the patients treated with thiopurines

  16. 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

  17. 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.

  18. 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}.

  19. Relation of burden of myocardial fibrosis to malignant ventricular arrhythmias and outcomes in Fabry disease.

    PubMed

    Krämer, Johannes; Niemann, Markus; Störk, Stefan; Frantz, Stefan; Beer, Meinrad; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2014-09-15

    The aim of this study was to investigate the impact of myocardial fibrosis in Fabry disease. Seventy-three patients with genetically confirmed Fabry disease were followed for 4.8 ± 2.4 years. In accordance with current guidelines, 57 patients received enzyme replacement therapy (ERT) after study inclusion, whereas 16 did not. At baseline and latest possible follow-up, myocardial fibrosis was assessed noninvasively by cardiac magnetic resonance, and biomarkers of collagen metabolism were determined. Holter electrocardiography and clinical follow-up at yearly intervals were used to monitor malignant ventricular arrhythmias (MVAs; nonsustained and sustained ventricular tachycardia and sudden cardiac death). In total, 48 patients (66%) showed fibrosis assessed by late enhancement (LE) at baseline, and 4 patients developed new LE during follow-up, 2 of them despite ERT. The 2 patients receiving ERT (1.4 ± 1.9% vs 2.5 ± 2.6%, p <0.001) and the patients not receiving ERT (0.5 ± 0.8% vs 0.7 ± 1.0%, p = 0.035) showed a progression of LE during follow-up. None of the patients displayed reductions of LE during follow-up. Collagen biomarkers were elevated in patients with and without LE but did not correlate with LE amount. Thirteen LE-positive patients at the baseline examination had documented MVAs (including 5 sudden cardiac deaths), whereas none of the patients without LE had MVAs. The yearly increase in fibrosis was 0.9 ± 0.6% in patients with MVAs and 0.2 ± 0.3% in patients without MVAs (p <0.001). Logistic multivariate regression analysis revealed that the annual increase in fibrosis during follow-up was the only independent predictor of MVAs. In conclusion, myocardial fibrosis in Fabry disease is progressive, apparently not modified by ERT, and a crucial outcome determinant.

  20. [Advances in the diagnostics of Alzheimer's disease].

    PubMed

    Fiedler, U; Wiltfang, J; Peters, N; Benninghoff, J

    2012-05-01

    Due to the demographic developments, diagnosis and treatment, dementia constitutes an increasing medical challenge and is likely to have an increasing socioeconomic impact. Dementia does not reflect a single disease but encompasses a variety of underlying conditions, heterogeneous clinical courses and therapeutic approaches, among which Alzheimer's disease represents the most common cause. Therefore, a thorough differential diagnosis of dementia is of major importance. To date the current diagnosis of dementia according to ICD-10/DMS-IV is based on clinical criteria. In addition, the concept of mild cognitive impairment comprises early cognitive dysfunction without clinically apparent dementia. Alzheimer's disease is more and more conceptualized as a disease continuum with mild cognitive impairment as an early and manifest dementia as the later stage of the disease. This review gives an overview on the current diagnostic approaches and the proposed revisions of diagnostic and research criteria for Alzheimer's disease.

  1. Interdisciplinary Management of Patient with Advanced Periodontal Disease.

    PubMed

    Kochar, Gagan Deep; Jayan, B; Chopra, S S; Mechery, Reenesh; Goel, Manish; Verma, Munish

    2016-01-01

    This case report describes the interdisciplinary management of an adult patient with advanced periodontal disease. Treatment involved orthodontic and periodontal management. Good esthetic results and dental relationships were achieved by the treatment.

  2. A fatal case of malignant atrophic papulosis (Degos' disease) in a man with factor V Leinden mutation and lupus anticoagulant.

    PubMed

    Hohwy, Thomas; Jensen, Martin Glümer; Tøttrup, Anders; Steiniche, Torben; Fogh, Karsten

    2006-01-01

    Malignant atrophic papulosis (Degos' disease) is a very rare condition characterized by atrophic papular skin lesions and variable association of systemic involvement. We describe a 33-year-old man who presented with a widespread skin eruption consistent with malignant atrophic papulosis. During the course of the disease he even developed penile ulcerations, a symptom that has been reported only a few times previously. He subsequently died of multiple perforations of the small bowel 2.5 years after onset of the disease. Laboratory investigations revealed a mutation of factor V Leiden and the presence of lupus anticoagulant, but no anti-cardiolipin antibodies. The patient was treated with narrow-band ultraviolet (UV)B, prednisolone and, later, aspirin, pentoxifyllin and warfarin. Despite this very intensive anticoagulant and anti-platelet therapy, the treatment had no effect on the skin lesions and could not prevent systemic involvement.

  3. Advancing swine models for human health and diseases.

    PubMed

    Walters, Eric M; Prather, Randall S

    2013-01-01

    Swine models are relatively new kids on the block for modeling human health and diseases when compared to rodents and dogs. Because of the similarity to humans in size, physiology, and genetics, the pig has made significant strides in advancing the understanding of the human condition, and is thus an excellent choice for an animal model. Recent technological advances to genetic engineering of the swine genome enhance the utility of swine as models of human genetic diseases.

  4. 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.

  5. Second acute leukemia and other malignancies following treatment for Hodgkin's disease

    SciTech Connect

    Valagussa, P.; Santoro, A.; Fossati-Bellani, F.; Banfi, A.; Bonadonna, G.

    1986-06-01

    The records of 1329 patients with Hodgkin's disease admitted from 1965 to 1982 were analyzed to assess the relative frequency of second neoplasms. Within a median follow-up of 9.5 years, a total of 68 new cancers were documented. Nineteen cases of acute nonlymphocytic leukemia, 6 cases of non-Hodgkin's lymphomas, and 43 cases with different types of solid tumors were identified. The overall risk of non-Hodgkin's lymphoma was 1.3% +/- 0.6% and of solid tumors was 8.3% +/- 1.5% when basal cell carcinomas were included and 6.7% +/- 1.4% when basal cell carcinomas were excluded. No cases of leukemia were documented in patients treated with radiation therapy only. The 12-year estimate of leukemia by treatment was as follows: chemotherapy only 1.4% +/- 2.3%; radiation plus MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) 10.2% +/- 5.2%; radiation plus ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) 0; and radiation plus other drug regimens 4.8% +/- 1.6%. The risk of leukemia was particularly high (15.5% +/- 7.4%) in patients who received salvage MOPP after radiation failure. A positive association was also noted between increasing age and risk of second malignancies, especially leukemia. The incidence of second neoplasms can be markedly decreased by deleting from potentially curative therapy certain drugs such as alkylating agents, procarbazine, and nitrosourea derivatives.

  6. Advances in management of sickle cell disease.

    PubMed

    Agarwal, M B

    2003-08-01

    Sickle cell disease is numerically as common as thalassaemia. However, it affects relatively under privileged population i.e. tribal population belonging to economically poor class and having inadequate access to education and modern health facilities. A recent explosion acknowledged in understanding the pathogenesis of this disease has lead to newer dimensions in treatment. Some of these viz. prevention of overwhelming bacterial infection, present indications and controversies regarding blood transfusion, prevention of stroke, acute chest syndrome, hydroxyurea therapy--probably the best disease modifying agent at the moment, stem cell transplantation--a cure and certain promising experimental therapies including gene therapy have been discussed in this review.

  7. Comprehensive banking of sibling donor cord blood for children with malignant and nonmalignant disease.

    PubMed

    Reed, William; Smith, Renée; Dekovic, Florinna; Lee, Joanna Y; Saba, Julie D; Trachtenberg, Elizabeth; Epstein, Joanna; Haaz, Steffany; Walters, Mark C; Lubin, Bertram H

    2003-01-01

    Banking of cord blood (CB) for unrelated hematopoietic stem cell (HSC) transplantation is well established. However, directed-donor banking of CB for siblings in a current good tissue practices (cGTP) environment has not previously been investigated. Families were eligible for the present study if they were caring for a child with a disorder treatable by HSC transplantation and expecting the birth of a full sibling. We devised standard operating procedures and policies to address eligibility, donor recruitment, donor and recipient evaluation, CB collection, shipping, graft characterization, storage, and release of CB from quarantine. Many of these policies are distinctly different from those established for unrelated-donor CB banks. We enrolled 540 families from 42 states. Collections occurred at several hundred different hospitals. No family was deferred on the basis of health history or infectious disease testing, but departures from standard donor suitability criteria were documented. Disease categories for sibling recipients included malignancy, sickle cell anemia, thalassemia major, nonmalignant hematological conditions, and metabolic errors. Mean CB volume (including anticoagulant) was 103.1 mL; mean nucleated cell count was 8.9 x 10(8). Cell dose exceeded 1.5 x 10(7) nucleated cells per kilogram for 90% of banked units. Seventeen units (3.4%) have been transplanted. Sixteen of the 17 CB allograft recipients had stable engraftment of donor cells. Remote-site collection of sibling donor CB can be accomplished with a high success rate and in a cGTP-guided environment. The cellular products have been used successfully for transplantation; their number and characteristics should be adequate to support the first prospective clinical investigations of sibling CB transplantation.

  8. Advances in Biomarker Research in Parkinson's Disease.

    PubMed

    Mehta, Shyamal H; Adler, Charles H

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease, and the numbers are projected to double in the next two decades with the increase in the aging population. An important focus of current research is to develop interventions to slow the progression of the disease. However, prerequisites to it include the development of reliable biomarkers for early diagnosis which would identify at-risk groups and disease progression. In this review, we present updated evidence of already known clinical biomarkers (such as hyposmia and rapid eye movement (REM) sleep behavior disorder (RBD)) and neuroimaging biomarkers, as well as newer possible markers in the blood, CSF, and other tissues. While several promising candidates and methods to assess these biomarkers are on the horizon, it is becoming increasingly clear that no one candidate will clearly fulfill all the roles as a single biomarker. A multimodal and combinatorial approach to develop a battery of biomarkers will likely be necessary in the future.

  9. Malignant mesothelioma

    PubMed Central

    Moore, Alastair J; Parker, Robert J; Wiggins, John

    2008-01-01

    Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis. PMID:19099560

  10. Second primary malignancy after Hodgkin's disease, ovarian cancer and cancer of the testis: a population-based cohort study.

    PubMed Central

    Coleman, M. P.; Bell, C. M.; Fraser, P.

    1987-01-01

    The risk of second primary malignancy was assessed in a population-based cohort study of all persons registered with Hodgkin's disease (n = 2,970), ovarian cancer (n = 11,802) and testicular cancer (n = 2,013) in the South Thames Cancer Registry during the period 1961-80, to identify for further study those second malignancies which might be treatment-related. A total of 244 second malignancies was observed. After adjustment for age, sex and calendar period, the relative risk of any second malignancy was 1.4 (90% confidence interval (CI) 1.1-1.7) after Hodgkin's disease, 1.1 (90% CI 1.0-1.2) after ovarian cancer and 0.7 (90% CI 0.5-1.0) after testicular cancer. In particular, the relative risk for leukaemia was 11.9 after Hodgkin's disease, 3.7 after ovarian cancer and 2.5 after testicular cancer. Excess risks were also observed for cancers of the cervix and lung after Hodgkin's disease, for cancers of the breast, lung and rectum after ovarian cancer, and for contralateral testicular cancer. Confounding by social class or smoking does not explain these observations. The excess risks of leukaemia and of second cancer were higher in patients first diagnosed with Hodgkin's disease and ovarian cancer in the 1970s than for those first diagnosed in the 1960s. Increased use of multiple-agent chemotherapy regimes for these tumours in the 1970s may have contributed to these increases in excess risk. PMID:3663481

  11. Primary pancreatic sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): an unusual extranodal manifestation clinically simulating malignancy.

    PubMed

    Podberezin, Mark; Angeles, Ronald; Guzman, Grace; Peace, David; Gaitonde, Sujata

    2010-02-01

    Abstract Sinus histiocytosis with massive lymphadenopathy (SHML), also called Rosai-Dorfman disease, is a rare entity. Its etiology and pathogenesis are still essentially unclear. The histologic hallmark of this disease is proliferation of distinctive histiocytes within lymph node sinuses and in extranodal sites. Approximately 23% of patients with SHML, documented in the SHML Registry, presented with disease primarily in extranodal sites, and very few cases of SHML (<1%) involving the gastrointestinal system have been described in the literature. We report an unusual case of primary pancreatic SHML with infiltration of the process into peripancreatic, perinephric, and perisplenic adipose tissue, simulating malignancy.

  12. 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.

  13. Advances in the genetics of Parkinson disease.

    PubMed

    Trinh, Joanne; Farrer, Matt

    2013-08-01

    Parkinson disease (PD) is a multifactorial neurodegenerative disease that was long considered the result of environmental factors. In the past 15 years, however, a genetic aetiology for PD has begun to emerge. Here, we review results from linkage and next-generation sequencing studies of familial parkinsonism, as well as candidate gene and genome-wide association findings in sporadic PD. In these studies, many of the genetic findings overlap, despite different designs and study populations, highlighting novel therapeutic targets. The molecular results delineate a sequence of pathological events whereby deficits in synaptic exocytosis and endocytosis, endosomal trafficking, lysosome-mediated autophagy and mitochondrial maintenance increase susceptibility to PD. These discoveries provide the rationale, molecular insight and research tools to develop neuroprotective and disease-modifying therapies.

  14. [Advances in chronic obstructive pulmonary disease].

    PubMed

    Jiménez, Belén Arnalich; Pumarega, Irene Cano; Ausiró, Anna Mola; Izquierdo Alonso, José Luis

    2009-01-01

    Although chronic obstructive pulmonary disease (COPD) is characterized by poorly reversible, chronic airflow obstruction, from the clinical point of view we must continue to make progress in the diagnosis and management of these patients so that spirometry is not the only technique used. Understanding that COPD is a heterogeneous process and that patient complexity usually increases due to the presence of comorbidities will allow more individualized strategies to be designed, which may improve control of the process. The TORCH and UPLIFT trials have shown that current treatment can improve important aspects of the disease, including mortality. However, the finalizing of these two large trials has generated a current of opinion favoring a more individually-tailored approach that should include all the factors -both pulmonary and extrapulmonary- that can modify the patient's form of presentation. Although we are witnessing a change in the therapeutic approach to COPD, future treatment will probably be based on studies performed in specific patient subgroups and on clarifying the interrelation between COPD and other diseases that are common in these patients. Greater knowledge of the pathogenesis of the disease may improve pharmacological treatment but drugs that, by themselves, alter the short- and longterm course of COPD are not on the horizon. However, a more patient-focussed approach may be the main tool available to physicians to increase quality of life -and possibly survival- in these patients.

  15. Advances in Pediatric Nonalcoholic Fatty Liver Disease

    PubMed Central

    Loomba, Rohit; Sirlin, Claude B.; Schwimmer, Jeffrey B.; Lavine, Joel E.

    2009-01-01

    Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in children and adolescents in the United States. A two- to three-fold rise in the rates of obesity and overweight in children over the last 2 decades is probably responsible for the epidemic of NAFLD. Emerging data suggest that children with NASH progress to cirrhosis which may ultimately increase liver-related mortality. More worrisome is the recognition that cardiovascular risk and morbidity in children and adolescents is associated with fatty liver. Pediatric fatty liver disease often displays a histologic pattern distinct from that found in adults. Liver biopsy remains the gold standard for diagnosis of NASH. Non-invasive biomarkers are needed to identify individuals with progressive liver injury. Targeted therapies to improve liver histology and metabolic abnormalities associated with fatty liver are needed. Currently, randomized-controlled trials are underway in the pediatric population to define pharmacologic therapy for NAFLD. Public health awareness and intervention are needed to promote healthy diet, exercise, and lifestyle modifications to prevent and reduce the burden of disease in the community. PMID:19637286

  16. Advanced therapeutic approach for the treatment of malignant pleural mesothelioma via the intrapleural administration of liposomal pemetrexed.

    PubMed

    Ando, Hidenori; Kobayashi, Sakiko; Abu Lila, Amr S; Eldin, Noha Essam; Kato, Chihiro; Shimizu, Taro; Ukawa, Masami; Kawazoe, Kazuyoshi; Ishida, Tatsuhiro

    2015-12-28

    Malignant pleural mesothelioma (MPM) is an aggressive cancer that proliferates in the pleural cavity. Pemetrexed (PMX) in combination with cisplatin is currently the approved standard care for MPM, but a dismal response rate persists. Recently, we prepared various liposomal PMX formulations using different lipid compositions and evaluated their in vitro cytotoxicity against human mesothelioma cells (MSTO-211H). In the present study, we investigated the in vivo therapeutic effect of our liposomal PMX formulations using an orthotopic MPM tumor mouse model. PMX encapsulated within either cholesterol-containing (PMX/Chol CL) or cholesterol-free (PMX/Non-Chol CL) cationic liposome was intrapleurally injected into tumor-bearing mice. PMX encapsulated in cholesterol-free liposomes (PMX/Non-Chol CL) drastically inhibited the tumor growth in the pleural cavity, while free PMX and PMX encapsulated in cholesterol-containing liposomes (PMX/Chol CL) barely inhibited the tumor growth. The enhanced in vivo anti-tumor efficacy of PMX/Non-Chol CL was credited, on the one hand, for prolonging the retention of cationic liposomes in the pleural cavity via their electrostatic interaction with the negatively charged membranes of tumor cells, but on the other hand, it was charged with contributing to a higher drug release from the "fluid" liposomal membrane following intrapleural administration. This therapeutic strategy of direct intrapleural administration of liposomal PMX, along with the great advances in CL-guided therapeutics, might be a promising therapeutic approach to conquering the poor prognosis for MPM.

  17. 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

  18. 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.

  19. A phase II study of REOLYSIN(®) (pelareorep) in combination with carboplatin and paclitaxel for patients with advanced malignant melanoma.

    PubMed

    Mahalingam, Devalingam; Fountzilas, Christos; Moseley, Jennifer; Noronha, Nicole; Tran, Hue; Chakrabarty, Romit; Selvaggi, Giovanni; Coffey, Matthew; Thompson, Brad; Sarantopoulos, John

    2017-04-01

    REOLYSIN(®) (pelareorep) is an investigational new drug, consisting of a live, replication-competent, Reovirus Type 3 Dearing strain in a proprietary formulation. Several preclinical and clinical trials with REOLYSIN(®) on a wide range of cancer indications have demonstrated antineoplastic activity on cells with activated RAS-signaling pathway. Furthermore, long-term survival benefits were evident in post-treatment patients indicating a potential antitumor immune response triggered by REOLYSIN(®). Numerous mono and/or combination therapy studies with the agent showed a consistent safety profile. The current study is a phase II, single-arm, open label trial of REOLYSIN(®) in combination with carboplatin and paclitaxel for patients with advanced melanoma. Results from the 14 patients enrolled in the study exhibited no grade 4 adverse events or deaths but manageable grade-3 toxicities commonly attributed to REOLYSIN(®), including pyrexia, chills, myalgia, pain, fatigue, and nausea. The number of treatment cycles ranged from 2 to 20 with a median of 6 cycles. The study met its treatment and efficacy goal for the first stage with three partial responses (ORR was 21%). No complete responses were noted. The median PFS and OS were 5.2 and 10.9 months, respectively. The 1-year OS was 43% with a disease control rate of 85%. In conclusion, REOLYSIN(®) combined with carboplatin and paclitaxel is a safe and potentially efficacious therapy for patients with advanced malignant melanoma. Additional combination studies using REOLYSIN(®) with chemo/immunotherapy drugs may support more favorable outcomes for patients in this indication.

  20. Refractory gastroesophageal reflux disease: advances and treatment.

    PubMed

    Ates, Fehmi; Francis, David O; Vaezi, Michael F

    2014-08-01

    'Refractory gastroesophageal reflux disease' is one of the most common misnomers in the area of gastroesophageal reflux disease. The term implies reflux as the underlying etiology despite unresponsiveness to aggressive proton pump inhibitor therapy. The term should be replaced with 'refractory symptoms.' We must acknowledge that in many patients symptoms of reflux often overlap with non-GERD causes such as gastroparesis, dyspepsia, hypersensitive esophagus and functional disorders. Lack of response to aggressive acid suppressive therapy often leads to diagnostic testing. In majority of patients these tests are normal. The role of non-acid reflux in this group is uncertain and patients should not undergo surgical fundoplication based on this parameter. In patients unresponsive to acid suppressive therapy GERD is most commonly not causal and a search for non-GERD causes must ensue.

  1. 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

  2. MR imaging of the female pelvis: current perspectives and review of genital tract congenital anomalies, and benign and malignant diseases.

    PubMed

    Patel, V H; Somers, S

    1997-10-01

    MR imaging continues to be an integral problem-solving modality in the evaluation of congenital anomalies and acquired diseases of the female genital tract organs and provides effective clinical information to the practicing gynecologist in those patients in whom sonography is technically suboptimal or the results are equivocal. This article describes the state-of-the art MR imaging of the female pelvis and addresses its current perspectives in the following sections: (1) technical aspects of MR in imaging the female pelvis, (2) normal pelvic anatomy and variations that are seen on MRI, (3) role of MRI in the diagnosis of congenital uterine and vaginal anomalies, (4) MR imaging approach to diagnose congenital uterine and vaginal anomalies, (5) advantages and limitations of MR in the evaluation of various benign diseases and malignant neoplasms of the female genital tract, (6) a MR staging system and criteria for each gynecologic malignancy, (7) fundamental MR criteria to differentiate benign from malignant tumors and recurrent tumors from fibrosis, and (8) the present cost-effective value of MR in pregnancy and obstetrics. Magnetic resonance (MR) technology continues to be an important problem-solving modality in the evaluation of benign, malignant, and recurrent diseases of the female pelvic organs with the development of new software and improved hardware over the last few years. The main issues addressed in this article are (1) to review the basic and expanded applications of the current state-of-the art MR imaging in the diagnosis and management of various congenital and acquired disorders of the female pelvic organs, (2) to illustrate a simplified clinico-radiologic (MRI) approach to the diagnosis of congenital and acquired pathologies of the pelvic organs, (3) to provide relevant information to the clinicians to make rational choices among the competing imaging modalities, and (4) to outline the future potential of this modality in the pelvis.

  3. Prostate cancer: 9. Treatment of advanced disease

    PubMed Central

    Gleave, M E; Bruchovsky, N; Moore, M J; Venner, P

    1999-01-01

    A 70-year-old man is referred to a urologist for recommendations on the management of metastatic prostate cancer. His cancer was diagnosed 5 years ago, and he underwent radical prostatectomy at that time. The tumour was confined to the prostate gland (Gleason score 7), and during surgery the lymph nodes were assessed as being clear of cancer. Before the surgery, the patient's prostate-specific antigen (PSA) level had been 8 ng/mL. After the prostatectomy, PSA was at first undetectable, but recently the PSA level rose to 2 ng/mL and then, at the most recent test, to 16 ng/mL. A bone scan was ordered to investigate back discomfort, which has been persistent but easily controlled with acetaminophen. Unfortunately, the bone scan shows several sites of metastatic disease. The man's medical history includes type 2 diabetes, which has developed during the past 3 years and which is controlled by diet, as well as asymptomatic hypertension, which is managed by means of a thiazide diuretic. The patient asks what treatments are available, what impact they are likely to have on his disease and what risks are associated with the therapies. PMID:9951446

  4. Hydroxycarbamine: from an Old Drug Used in Malignant Hemopathies to a Current Standard in Sickle Cell Disease

    PubMed Central

    Cannas, Giovanna; Poutrel, Solène; Thomas, Xavier

    2017-01-01

    While hydroxycarbamide (hydroxyurea, HU) has less and fewer indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support for safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. No increased incidence of leukemia and teratogenicity was demonstrated. HU has become the standard-of-care for sickle cell anemia but remains underused. Barriers to its use should be identified and overcome. PMID:28293403

  5. Therapeutic drug monitoring of monoclonal antibodies in inflammatory and malignant disease: Translating TNF-α experience to oncology.

    PubMed

    Oude Munnink, T H; Henstra, M J; Segerink, L I; Movig, K L L; Brummelhuis-Visser, P

    2016-04-01

    Lack of response to monoclonal antibodies (mAbs) has been associated with inadequate mAb serum concentrations. Therapeutic drug monitoring (TDM) of mAbs has the potential to guide to more effective dosing in individual patients. This review discusses the mechanisms responsible for interpatient variability of mAb pharmacokinetics, summarizes exposure-response data of mAbs used in inflammatory and malignant disease, presents current evidence of mAb-TDM in inflammatory disease, and provides hurdles and required future steps for further implementing mAb-TDM.

  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. Advances in environmental and occupational respiratory disease in 2010.

    PubMed

    Peden, David B; Bush, Robert K

    2011-03-01

    2010 Found a number of significant advances in environmental and occupational respiratory disease. The role of sensitization and the subsequent production of allergic disease have been explored. New allergens and their T- and B-cell epitopes have been characterized. Novel approaches to the diagnosis and evaluation of food allergy have been described. The role of pollutants as they affect respiratory disease and the effects of age extremes on sensitization and asthma have been addressed. Significant advances in the understanding of inflammatory changes in both the upper and lower respiratory systems occurred. Novel therapeutic approaches have been explored, including the development of hypoallergens from improved molecular biology techniques. New effective approaches to asthma therapy have been identified. Exposure reduction through air filtration and novel immunotherapy approaches, such as sublingual therapy, have made significant advances.

  8. Alzheimer's disease: recent advances and future perspectives.

    PubMed

    Ubhi, Kiren; Masliah, Eliezer

    2013-01-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory deficits and other cognitive disturbances. Neuropathologically, AD is characterized by the progressive loss of basal forebrain cholinergic neurons that innervate the hippocampus and cortex and the abnormal extracellular accumulation of amyloid-β and intracellular tau protein. Current research on AD is focused on the mechanisms underlying the abnormal oligomerization, fibrillation, and accumulation of the amyloid-β and tau proteins, mechanisms that may alter the dynamics of this accumulation and on experimental therapeutics approaches aimed at the clearance of the abnormally folded proteins and other potentially neuroprotective interventions. This review will summarize the main areas of investigation in AD and present ways forward for future work.

  9. 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.

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

    PubMed

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

    2016-01-01

    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.

  11. 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

  12. Glucocerebrosidase and Parkinson disease: Recent advances.

    PubMed

    Schapira, Anthony H V

    2015-05-01

    Mutations of the glucocerebrosidase (GBA) gene are the most important risk factor yet discovered for Parkinson disease (PD). Homozygous GBA mutations result in Gaucher disease (GD), a lysosomal storage disorder. Heterozygous mutations have not until recently been thought to be associated with any pathological process. However, it is clear that the presence of a GBA mutation in homozygous or heterozygous form is associated with an approximately 20-fold increase in the risk for PD, with little if any difference in risk burden related to gene dose. Most studies suggest that 5-10% of PD patients have GBA mutations, although this figure is greater in the Ashkenazi population and may be an underestimate overall if the entire exome is not sequenced. GBA-associated PD is clinically indistinguishable from idiopathic PD, except for slightly earlier age of onset and a greater frequency of cognitive impairment. Pathological and imaging features, and response to pharmacotherapy are identical to idiopathic PD. GBA mutations result in reduced enzyme activity and mutant protein may become trapped in the endoplasmic reticulum (ER) leading to unfolded protein response and ER associated degradation and stress. Both mechanisms may be relevant in GD and PD pathogenesis and lead to impaired lysosomal function. Of particular relevance to PD is the interaction of glucocerebrosidase enzyme (GCase) with alpha-synuclein (SNCA). There appears to be a bi-directional reciprocal relationship between GCase levels and those of SNCA. Thus reduced GCase in GBA mutation PD brain is associated with increased SNCA, and increased SNCA deposition is associated with reduced GCase even in GBA wild-type PD brains. It is noteworthy that GBA mutations are also associated with an increase in risk for dementia with Lewy bodies, another synucleinopathy. It has been suggested that the relationship between GCase and SNCA may be leveraged to reduce SNCA levels in PD by enhancing GCase levels and activity. This

  13. Advances in Diagnosis and Management of Salivary Gland Diseases

    PubMed Central

    Rice, Dale H.

    1984-01-01

    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. PMID:6328773

  14. Malignant peripheral nerve sheath tumor of adrenal gland with heterologus osseous differentiation in a case of Von Recklinghausen's disease.

    PubMed

    Baisakh, Manas R; Mohapatra, Nachiketa; Adhikary, Samiran D; Routray, Debasis

    2014-01-01

    Malignant peripheral nerve sheath tumor (MPNST) of the adrenal gland is extremely rare. Most of them occur in association with neurofibromatosis, ganglioneuroma or as part of a composite tumor such as pheochromocytoma. Only seven cases of MPNST of the adrenal gland have been reported in the literature till date. Discriminating this entity from other soft tissue sarcomas and gastrointestinal stromal tumor of the adrenal gland has important diagnostic and therapeutic implications. Moreover, the tumor size and pattern of expression for certain immunohistochemical markers may serve as independent predictors of aggressiveness. Herein we present a 24-years-old male with features of Von Recklinghausen's disease who presented with large left adrenal gland malignant peripheral nerve sheath tumor.

  15. 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

  16. Diagnostic Utility of Pleural Fluid Cell Block versus Pleural Biopsy Collected by Flex-Rigid Pleuroscopy for Malignant Pleural Disease: A Single Center Retrospective Analysis

    PubMed Central

    Sasada, Shinji; Izumo, Takehiro; Matsumoto, Yuji; Tsuchida, Takaaki

    2016-01-01

    Background Some trials recently demonstrated the benefit of targeted treatment for malignant disease; therefore, adequate tissues are needed to detect the targeted gene. Pleural biopsy using flex-rigid pleuroscopy and pleural effusion cell block analysis are both useful for diagnosis of malignancy and obtaining adequate samples. The purpose of our study was to compare the diagnostic utility between the two methods among patients with malignant pleural disease with effusion. Methods Data from patients who underwent flex-rigid pleuroscopy for diagnosis of pleural effusion suspicious for malignancy at the National Cancer Center Hospital, Japan between April 2011 and June 2014 were retrospectively reviewed. All procedures were performed under local anesthesia. At least 150 mL of pleural fluid was collected by pleuroscopy, followed by pleural biopsies from the abnormal site. Results Thirty-five patients who were finally diagnosed as malignant pleural disease were included in this study. Final diagnoses of malignancy were 24 adenocarcinoma, 1 combined adeno-small cell carcinoma, and 7 malignant pleural mesothelioma (MPM), and 3 metastatic breast cancer. The diagnostic yield was significantly higher by pleural biopsy than by cell block [94.2% (33/35) vs. 71.4% (25/35); p = 0.008]. All patients with positive results on cell block also had positive results on pleural biopsy. Eight patients with negative results on cell block had positive results on pleural biopsy (lung adenocarcinoma in 4, sarcomatoid MPM in 3, and metastatic breast cancer in 1). Two patients with negative results on both cell block and pleural biopsy were diagnosed was sarcomatoid MPM by computed tomography-guided needle biopsy and epithelioid MPM by autopsy. Conclusion Pleural biopsy using flex-rigid pleuroscopy was efficient in the diagnosis of malignant pleural diseases. Flex-rigid pleuroscopy with pleural biopsy and pleural effusion cell block analysis should be considered as the initial diagnostic

  17. [Recent advances in immunologic laboratory testing for rheumatic diseases].

    PubMed

    Akahoshi, Tohru

    2004-09-01

    Immunologic laboratory tests serve critical roles in the care of patients with various rheumatic diseases. These tests can provide relevant information of rheumatic diseases based on their immunopathophysiological condition. Although immunologic laboratory tests are quite useful for the determination of diagnosis and the estimation of disease activity, organ involvement and prognosis, they are frequently misused and resulted in an inappropriate diagnosis and treatment. Appropriate use of immunologic laboratory tests and accurate clinical interpretation of the test results can prevent false diagnosis and unnecessary treatment. In order to improve clinical care of patients with rheumatic diseases, clinicians caring patients with rheumatic disease should recognize meanings, characteristics and limitations of each result of immunologic laboratory testing. This article reviewed recent advances in immunologic laboratory testing such as antinuclear antibody, anti-DNA antibody and anti-neutrophil cytoplasmic antibody, and introduced guidelines for these testing. These guidelines based on evidences of EBM may contribute to the appropriate use of immunologic laboratory tests for rheumatic diseases.

  18. Emerging and Neglected Infectious Diseases: Insights, Advances, and Challenges

    PubMed Central

    2017-01-01

    Infectious diseases are a significant burden on public health and economic stability of societies all over the world. They have for centuries been among the leading causes of death and disability and presented growing challenges to health security and human progress. The threat posed by infectious diseases is further deepened by the continued emergence of new, unrecognized, and old infectious disease epidemics of global impact. Over the past three and half decades at least 30 new infectious agents affecting humans have emerged, most of which are zoonotic and their origins have been shown to correlate significantly with socioeconomic, environmental, and ecological factors. As these factors continue to increase, putting people in increased contact with the disease causing pathogens, there is concern that infectious diseases may continue to present a formidable challenge. Constant awareness and pursuance of effective strategies for controlling infectious diseases and disease emergence thus remain crucial. This review presents current updates on emerging and neglected infectious diseases and highlights the scope, dynamics, and advances in infectious disease management with particular focus on WHO top priority emerging infectious diseases (EIDs) and neglected tropical infectious diseases. PMID:28286767

  19. Association of high mobility group BOX-1 and receptor for advanced glycation endproducts with clinicopathological features of haematological malignancies: a systematic review

    PubMed Central

    Bhavsar, Sheila B.; Riley, Erinn M.; Caponetti, Gabriel C.; Agrawal, Devendra K.

    2017-01-01

    High-mobility group box 1 (HMGB1) is a versatile protein with nuclear and extracellular functions. In the extracellular milieu, HMGB1 binds to several receptors, notably the receptor for advanced glycation end-products (RAGE). The expressions of HMGB1 and RAGE have been described in a variety of cancers. However, the clinical values of HMGB1 and RAGE in haematological malignancies have yet to be evaluated. A systematic search through PubMed and the Web of Science for articles discussing the role of HMGB1 and RAGE in haematological malignancies produced 15 articles. Overexpression of HMGB1 was reported to be associated with malignancy and, in certain studies, poor prognosis and tumour aggressiveness. Only one included study investigated the clinical value of RAGE, in which no significant difference was found between expression of RAGE in CLL neoplastic cells and nonmalignant controls. The discussed associations of HMGB1 and RAGE with clinicopathological characteristics of patients with haematological malignancies warrants further investigation into the prognostic and diagnostic value of both of these molecules. PMID:28239277

  20. First-in-human phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies

    PubMed Central

    Neidhart, Jeffrey D.; Ramanathan, Ramesh K.; Bassett, Dawn; Neidhart, James A.; Choi, Chung Hang J.; Chow, Warren; Chung, Vincent; Forman, Stephen J.; Garmey, Edward; Hwang, Jungyeon; Kalinoski, D. Lynn; Koczywas, Marianna; Longmate, Jeffrey; Melton, Roger J.; Morgan, Robert; Oliver, Jamie; Peterkin, Joanna J.; Ryan, John L.; Schluep, Thomas; Synold, Timothy W.; Twardowski, Przemyslaw; Davis, Mark E.; Yen, Yun

    2013-01-01

    Summary Patients with advanced solid malignancies were enrolled to an open-label, single-arm, dose-escalation study, in which CRLX101 was administered intravenously over 60 min among two dosing schedules, initially weekly at 6, 12, and 18 mg/m2 and later bi-weekly at 12, 15, and 18 mg/m2. The maximum tolerated dose (MTD) was determined at 15 mg/m2 bi-weekly, and an expansion phase 2a study was completed. Patient samples were obtained for pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Response was evaluated per RECIST criteria v1.0 every 8 weeks. Sixty-two patients (31 male; median age 63 years, range 39-79) received treatment. Bi-weekly dosing was generally well tolerated with myelosuppression being the dose-limiting toxicity. Among all phase 1/2a patients receiving the MTD (n=44), most common grade 3/4 adverse events were neutropenia and fatigue. Evidence of systemic plasma exposure to both the polymer-conjugated and unconjugated CPT was observed in all treated patients. Mean elimination unconjugated CPT Tmax values ranged from 17.7 to 24.5 h, and maximum plasma concentrations and areas under the curve were generally proportional to dose for both polymer-conjugated and unconjugated CPT. Best overall response was stable disease in 28 patients (64 %) treated at the MTD and 16 (73 %) of a subset of NSCLC patients. Median progression-free survival (PFS) for patients treated at the MTD was 3.7 months and for the subset of NSCLC patients was 4.4 months. These combined phase 1/2a data demonstrate encouraging safety, pharmacokinetic, and efficacy results. Multinational phase 2 clinical development of CRLX101 across multiple tumor types is ongoing. PMID:23397498

  1. Novel phase I study combining G1 phase, S phase, and G2/M phase cell cycle inhibitors in patients with advanced malignancies

    PubMed Central

    Jain, Rajul K; Hong, David S; Naing, Aung; Wheler, Jennifer; Helgason, Thorunn; Shi, Nai-Yi; Gad, Yash; Kurzrock, Razelle

    2015-01-01

    PURPOSE: Cancer is a manifestation of aberrant cellular proliferation, and the cell cycle is one of the most successfully drugged targets in oncology. No prior study has been reported that simultaneously targets the 3 principal cell cycle phases populated by proliferating cells - G1, S, and G2/M. METHODS: Temsirolimus (G1 inhibitor), topotecan (S inhibitor), and bortezomib (G2/M inhibitor) were administered in combination to patients with advanced malignancies using a 3+3 dose escalation schedule to assess the safety and establish the maximum tolerated dose (primary endpoints) of this cell cycle targeting approach. An in silico pharmacodynamic model using established effects of each of these agents on the cell cycle was used to validate the regimen and to guide the dosing regimen. RESULTS: Sixty-two subjects were enrolled. The most common adverse events and dose-limiting toxicities were cytopenias, consistent with the cell cycle targeting approach employed. All cytopenias resolved to baseline values upon holding study drug administration. The maximum tolerated dose was temsirolimus 15 mg/kg IV D1, 8, 15; topotecan 2.8 mg/m2 IV D1, 8; and bortezomib 0.9 mg/m2 IV D1, 4, 8, 11 of a 21-day cycle. In silico modeling suggests the regimen induces cell population shifts from G2/M and S phases to G1 phase and the quiescent G0 phase. Eighteen percent of subjects (11/62) achieved partial response (n = 2, serous ovarian and papillary thyroid) or stable disease for > 6 months (n = 9). CONCLUSION: Combining drugs with inhibitory activity of G1 phase, S phase, and G2/M phase is safe and warrants further evaluation. PMID:26467427

  2. Advances in environmental and occupational respiratory disease in 2007.

    PubMed

    Bush, Robert K; Peden, David

    2008-06-01

    This review of key articles appearing in the Journal in 2008 represents significant advances in the understanding of the interrelationships between the environment and allergic respiratory diseases. New allergens have been identified and characterized. Improvements in diagnostic techniques and methods to assess environmental allergen exposure have been developed. The novel therapeutics and refinements of allergen avoidance approaches will improve patient care. A fuller appreciation of the complexities of environmental factors in allergic diseases can lead to better preventative measures. Lastly, the increasingly important role of pollutants on inflammatory processes is evolving. The articles discussed will add to our increasing knowledge base and advance the ability to more effectively treat patients with allergic respiratory diseases and expand research opportunities.

  3. 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.

  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. Recent advances in metabolomics in neurological disease, and future perspectives.

    PubMed

    Zhang, Ai-hua; Sun, Hui; Wang, Xi-jun

    2013-10-01

    Discovery of clinically relevant biomarkers for diseases has revealed metabolomics has potential advantages that classical diagnostic approaches do not. The great asset of metabolomics is that it enables assessment of global metabolic profiles of biofluids and discovery of biomarkers distinguishing disease status, with the possibility of enhancing clinical diagnostics. Most current clinical chemistry tests rely on old technology, and are neither sensitive nor specific for a particular disease. Clinical diagnosis of major neurological disorders, for example Alzheimer's disease and Parkinson's disease, on the basis of current clinical criteria is unsatisfactory. Emerging metabolomics is a powerful technique for discovering novel biomarkers and biochemical pathways to improve diagnosis, and for determination of prognosis and therapy. Identifying multiple novel biomarkers for neurological diseases has been greatly enhanced with recent advances in metabolomics that are more accurate than routine clinical practice. Cerebrospinal fluid (CSF), which is known to be a rich source of small-molecule biomarkers for neurological and neurodegenerative diseases, and is in close contact with diseased areas in neurological disorders, could potentially be used for disease diagnosis. Metabolomics will drive CSF analysis, facilitate and improve the development of disease treatment, and result in great benefits to public health in the long-term. This review covers different aspects of CSF metabolomics and discusses their significance in the postgenomic era, emphasizing the potential importance of endogenous small-molecule metabolites in this emerging field.

  6. 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

  7. 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

  8. 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

  9. Advances in celiac disease and gluten-free diet.

    PubMed

    Niewinski, Mary M

    2008-04-01

    Celiac disease is becoming an increasingly recognized autoimmune enteropathy caused by a permanent intolerance to gluten. Once thought to be a rare disease of childhood characterized by diarrhea, celiac disease is actually a multisystemic disorder that occurs as a result of an immune response to ingested gluten in genetically predisposed individuals. Screening studies have revealed that celiac disease is most common in asymptomatic adults in the United States. Although considerable scientific progress has been made in understanding celiac disease and in preventing or curing its manifestations, a strict gluten-free diet is the only treatment for celiac disease to date. Early diagnosis and treatment, together with regular follow-up visits with a dietitian, are necessary to ensure nutritional adequacy and to prevent malnutrition while adhering to the gluten-free diet for life. The purpose of this review is to provide clinicians with current updated information about celiac disease, its diverse clinical presentation and increased prevalence, the complex pathophysiology and strong genetic predisposition to celiac disease, and its diagnosis. This review focuses in detail on the gluten-free diet and the importance of intense expert dietary counseling for all patients with celiac disease. Recent advances in the gluten-free diet include food allergen labeling as well as the US Food and Drug Administration's proposed definition of the food-labeling term gluten-free. The gluten-free diet is complex and patients need comprehensive nutrition education from a skilled dietitian.

  10. ePTFE/FEP-Covered Metallic Stents for Palliation of MalignantBiliary Disease: Can Tumor Ingrowth Be Prevented?

    SciTech Connect

    Hatzidakis, Adam Krokidis, Miltiadis; Kalbakis, Kostantinos; Romanos, Jiannis; Petrakis, Ioannis; Gourtsoyiannis, Nicholas

    2007-09-15

    Purpose. To determine the application and clinical effectiveness of ePTFE/FEP-covered metallic stents for palliation of malignant biliary disease, and to evaluate the efficiency of stent coverage in preventing tumor ingrowth. Methods. During a 3-year period, 36 patients with malignant obstructive jaundice were treated with ePTFE/FEP-covered stents, with or without proximal side holes. The stricture was located in the lower common bile duct (CBD) in 18 cases, the upper CBD in 9, the lower common hepatic duct (CHD) in 6, and the upper CHD in 3 patients. Results.Thirty-seven covered stents were percutaneously implanted. The technical success rate was 97%. Reintervention was required in 6 cases. The 30-day mortality rate was 40%, not procedure-related. Mean survival was 128 days. Primary patency rates were 100%,55.5%, and 25% at 3, 6, and 12 months, respectively, while the assisted patency rate was 100% at 12 months. Stents without side holes had higher primary patency rates compared with those with side holes, where occlusion was always due to tumor ingrowth. Tumor ingrowth did not occur in the completely covered stents. No stent dysfunction due to sludge incrustation was found.Complications were 1 case of arterial laceration that occurred during percutaneous transhepatic cholangiography, and a subcapsular hematoma and 1 case of bile peritonitis, that both occurred during primary stenting. No complications followed the secondary stenting technique. Conclusion. ePTFE/FEP-covered metallic stents are safe and effective for palliation of malignant biliary disease. The presence of the ePTFE/FEP coating is likely to prevent from tumor ingrowth.

  11. 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

  12. Hodgkin disease therapy induced second malignancy susceptibility 6q21 functional variants in roma and hungarian population samples.

    PubMed

    Varszegi, Dalma; Duga, Balazs; Melegh, Bela I; Sumegi, Katalin; Kisfali, Peter; Maasz, Anita; Melegh, Bela

    2014-07-01

    Patients treated successfully for pediatric Hodgkin's lymphoma are known to develop secondary malignancies; care is already taken in treatment to prevent this adverse effect. Recent GWAS study identified rs4946728 and rs1040411 noncoding SNPs located between PRDM1 and ATG1 genes on chromosome 6q21 as risk factors for secondary malignancies in patients formerly treated with radiotherapy for pediatric Hodgkin disease. We investigated the allele frequencies of these two SNPs in biobanked, randomly selected DNA of average, apparently healthy Hungarians (n = 277) and in samples of Roma (n = 279) population living Hungary. The risk allele frequency for rs4946728 was 79.4 % in Hungarian and 83.5 % in Roma samples, while for rs1040411 it was 56.4 % in Hungarian and 55.8 % in Roma samples. These values are quite similar in the two populations, and are rather high. The values are higher than those frequencies observed in the controls (rs4946728: 59.1 % and rs1040411: 39.6 %, p < 0.05), and are in the range of the cases (86 % and 68.2 %, respectively) of the above original GWAS study. Our findings suggest, that beside the already taken precautions, genetic characterization of Hungarian pediatric Hodgkin patients seems to be advantageous prior to the treatment of their disease.

  13. Allogeneic CD34+ -selected peripheral stem cell transplantation from parental donors in children with non-malignant diseases.

    PubMed

    Kremens, B; Basu, O; Peceny, R; Grosse-Wilde, H; Schaefer, U W; Havers, W

    2002-01-01

    Allogeneic peripheral stem cell transplantation in six children with non-malignant hematologic or metabolic diseases which are eventually fatal was carried out with parental donors. Given three to five HLA mismatches, all grafts underwent CD34+ cell selection as graft-versus-host prophylaxis. The patients received median doses of 16.7 x 10(6) CD34+ cells/kg and 1.2 x 10(4) CD3+ cells/kg. All transplants engrafted. Neutrophils >0.5/nl were reached on day 11 (9-19) and platelets >50/nl on day 13 (10-25). Acute GVHD responding to steriods occured in three of six patients; it was restricted to the skin and overall did not exceed grade I. Two patients died of viral infections and four are alive with stable blood counts for 13, 15, 25 and 26 months. For children with non-malignant diseases which will eventually be fatal and which can be cured or ameliorated by allogeneic BMT, CD34+-selected stem cell transplants from mismatched or even haploidentical parents can be used if no other suitable donor is available. With high CD34+ cell doses and low CD3+ cell numbers, engraftment and avoidance of acute GVHD can be expected. Infections after transplantation remain the primary threat to survival.

  14. [Case of abdominal wall malignant peripheral nerve sheath tumor which is difficult to distinguish from a urachal disease].

    PubMed

    Tatenuma, Tomoyuki; Sakata, Ryoko; Sugiura, Shinpei; Tajiri, Takehiro; Gondo, Toshikazu; Kitami, Kazuo

    2013-09-01

    Malignant peripheral nerve sheath tumors (MPNST) are highly malignant soft tissue sarcomas. It is very rare for MPNST to arise in the abdominal wall. We report a case of abdominal wall MPNST that was difficult to distinguish from a urachal disease. A 72-year-old woman found a mass of the umbilicus in October 2011. She visited a digestive surgery department in November because it gradually enlarged. Diagnostic imaging suggested a urachal tumor. She was then referred to our clinic. Contrast enhanced CT showed that the 5-cm cystic tumor extended from the umbilicus to abdominal wall. The tumor showed low uptake value in PET-CT. We diagnosed her with a urachal cyst, but could not deny urachal carcinoma. Therefore, we performed surgical resection in January 2012. The pathological diagnosis was MPNST. She has not experienced recurrence for 9 months. MPNST mostly occur in the retroperitoneum close to the spine, extremities, head, and neck. It is very rare for them to occur in the abdominal wall. This is the sixth case including overseas reports. In addition, this is the first case in which it was difficult to distinguish from a urachal disease.

  15. Glutathione peroxidase in early and advanced Parkinson's disease.

    PubMed Central

    Johannsen, P; Velander, G; Mai, J; Thorling, E B; Dupont, E

    1991-01-01

    A defective antioxidant scavenging system plays a major role in one of the theories of the pathogenesis of Parkinson's disease. The aim of this study was to investigate whether there is a general difference in antioxidant activity between early and advanced cases of Parkinson's disease. Twenty five recently diagnosed patients, without any clinical fluctuations (group A), and 25 patients in a late phase of the disease with severe fluctuations in response to levodopa therapy (group B) were included in the study. Erythrocyte glutathione peroxidase was determined as a measure of antioxidant activity and significantly lower values were found in group B than in group A. Regression analyses in groups A and B showed significant correlation between glutathione peroxidase and duration of disease, but not between glutathione peroxidase and age of patients. Images PMID:1940936

  16. Miscellaneous indications in bone scintigraphy: metabolic bone diseases and malignant bone tumors.

    PubMed

    Cook, Gary J R; Gnanasegaran, Gopinath; Chua, Sue

    2010-01-01

    The diphosphonate bone scan is ideally suited to assess many global, focal or multifocal metabolic bone disorders and there remains a role for conventional bone scintigraphy in metabolic bone disorders at diagnosis, investigation of complications, and treatment response assessment. In contrast, the role of bone scintigraphy in the evaluation of primary malignant bone tumors has reduced with the improvement of morphologic imaging, such as computed tomography and magnetic resonance imaging. However, an increasing role for (18)F-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography is emerging as a functional assessment at diagnosis, staging, and neoadjuvant treatment response assessment.

  17. Advancing digital methods in the fight against communicable diseases.

    PubMed

    Chabot-Couture, Guillaume; Seaman, Vincent Y; Wenger, Jay; Moonen, Bruno; Magill, Alan

    2015-03-01

    Important advances are being made in the fight against communicable diseases by using new digital tools. While they can be a challenge to deploy at-scale, GPS-enabled smartphones, electronic dashboards and computer models have multiple benefits. They can facilitate program operations, lead to new insights about the disease transmission and support strategic planning. Today, tools such as these are used to vaccinate more children against polio in Nigeria, reduce the malaria burden in Zambia and help predict the spread of the Ebola epidemic in West Africa.

  18. 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%).

  19. Nutrition Intervention for Advanced Stages of Diabetic Kidney Disease

    PubMed Central

    Kalantar-Zadeh, Kamyar

    2015-01-01

    IN BRIEF For the goals of reducing diabetic kidney disease (DKD) onset and progression, approaches to nutritional therapy are a subject of much debate. This article discusses selected nutrients that have a role in affecting DKD outcomes and introduces application of newer, individualized concepts for healthful eating, as supported by clinical evidence relevant to patients with DKD. Selected aspects of management of advanced DKD are also reviewed. PMID:26300611

  20. Nutrition Intervention for Advanced Stages of Diabetic Kidney Disease.

    PubMed

    Goldstein-Fuchs, Jordi; Kalantar-Zadeh, Kamyar

    2015-08-01

    IN BRIEF For the goals of reducing diabetic kidney disease (DKD) onset and progression, approaches to nutritional therapy are a subject of much debate. This article discusses selected nutrients that have a role in affecting DKD outcomes and introduces application of newer, individualized concepts for healthful eating, as supported by clinical evidence relevant to patients with DKD. Selected aspects of management of advanced DKD are also reviewed.

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

    PubMed

    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

    2016-05-01

    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 (2(nd), or 3(rd) 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.

  2. 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

  3. 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

  4. Kikuchi-Fujimoto Disease with 18F-Fludeoxyglucose Uptake in Cervical Lymph Nodes on Dual-time-point Imaging Positron Emission Tomography/Computed Tomography Mimicking Malignant Disease

    PubMed Central

    Aoyama, Ken-ichi; Otsuru, Mitsunobu; Uchibori, Masahiro; Ota, Yoshihide

    2017-01-01

    Kikuchi-Fujimoto disease (KFD) is a benign but self-limiting disorder. However, KFD is often misdiagnosed as a malignant disease. Although 18F-fludeoxyglucose (FDG) uptake on dual-time-point imaging (DTPI) positron emission tomography (PET)/computed tomography (CT) is useful in distinguishing malignant from benign disease, the latter sometimes mimics malignancy on DTPI PET/CT, resulting in a misdiagnosis. Here, we describe the case of a 30-year-old woman who complained of cervical lymphadenopathy. PET showed increased FDG uptake in multiple lymph nodes, with a maximum standardized uptake value (SUVmax) of 19.0 in the early phase to 21.8 in the late phase. A biopsy was performed, and pathological examination revealed KFD. KFD with FDG uptake in lymph nodes on DTPI PET/CT is rare and difficult to be distinguished from a malignant disease. PMID:28217024

  5. Clinical Implications of High-mobility Group Box-1 (HMGB1) and the Receptor for Advanced Glycation End-products (RAGE) in Cutaneous Malignancy: A Systematic Review.

    PubMed

    Nguyen, Austin Huy; Detty, Shannon Q; Agrawal, Devendra K

    2017-01-01

    Inflammation and the immune system play a role in the development and progression of melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). The pro-inflammatory and tumor-promoting effects of the high-mobility group box-1 (HMGB1) protein and the receptor for advanced glycation end products (RAGE) have been investigated in these cutaneous malignancies. The clinical implication of these molecules is not fully described. The National Library of Medicine database was searched for articles addressing the clinical relevance of HMGB1 and RAGE in melanoma, BCC, and SCC. This systematic review includes nine articles, with six summarizing RAGE in cutaneous malignancies and three involving HMGB1. RAGE has been found to be up-regulated in SCC lesions, as well as melanoma. Levels of RAGE were highest in stage IV melanomas. Lower levels of soluble RAGE have been associated with poor overall survival in melanoma. Sporadic extracellular expression of HMGB1 was evident in BCC and SCC lesions, which could be released by necrotic tumor cells. HMGB1 was found to be a prognostic marker in melanoma, and HMGB1 levels were elevated in patients who were non-responders to ipilimumab treatment. HMGB1 and RAGE could serve as potential prognostic markers or therapeutic targets in treating melanoma, BCC, and SCC, but further research regarding the clinical utility of the HMGB1-RAGE axis in cutaneous malignancies is warranted.

  6. Cerebrovascular Disease in Children: Recent Advances in Diagnosis and Management

    PubMed Central

    Bowers, Karen J.; deVeber, Gabrielle A.; Ferriero, Donna M.; Roach, E. Steve; Vexler, Zinaida S.; Maria, Bernard L.

    2017-01-01

    Cerebrovascular disease in children manifests in many forms, all of which have devastating and long-lasting effects. Recent advances in diagnostic imaging have revealed that this condition is much more common in the pediatric population than previously believed, affecting as many as 1 in 1500 neonates and 1 in 3000 children. The underlying mechanisms that cause stroke—ischemic stroke, sinovenous thrombosis, and hemorrhagic stroke—are only beginning to be understood; however, progress has been made toward better understanding the mechanisms of disease, particularly in the fields of genetics, inflammation, and thrombus formation. Furthermore, new imaging techniques, and better understanding of how to use imaging in managing stroke, have enabled practitioners to more quickly and accurately identify cerebrovascular disease type in children, which is key to mitigation of negative outcomes. The 2010 Neurobiology of Disease in Children symposium, held in conjunction with the 39th annual meeting of the Child Neurology Society, aimed to (1) describe clinical issues surrounding childhood stroke, including diagnosis and acute care; (2) discuss recent advances in the understanding of the pathogenesis of childhood stroke; (3) review current management of and therapies for childhood stroke, including controversial therapies; and (4) establish research directions for investigators. This article summarizes the speakers’ presentations and includes an edited transcript of question-and-answer sessions. PMID:21778188

  7. 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.

  8. Advance care planning uptake among patients with severe lung disease: a randomised patient preference trial of a nurse-led, facilitated advance care planning intervention

    PubMed Central

    Sinclair, Craig; Auret, Kirsten Anne; Evans, Sharon Frances; Williamson, Fiona; Dormer, Siobhan; Greeve, Kim; Koay, Audrey; Price, Dot; Brims, Fraser

    2017-01-01

    Objective Advance care planning (ACP) clarifies goals for future care if a patient becomes unable to communicate their own preferences. However, ACP uptake is low, with discussions often occurring late. This study assessed whether a systematic nurse-led ACP intervention increases ACP in patients with advanced respiratory disease. Design A multicentre open-label randomised controlled trial with preference arm. Setting Metropolitan teaching hospital and a rural healthcare network. Participants 149 participants with respiratory malignancy, chronic obstructive pulmonary disease or interstitial lung disease. Intervention Nurse facilitators offered facilitated ACP discussions, prompted further discussions with doctors and loved ones, and assisted participants to appoint a substitute medical decision-maker (SDM) and complete an advance directive (AD). Outcome measures The primary measure was formal (AD or SDM) or informal (discussion with doctor) ACP uptake assessed by self-report (6 months) and medical notes audit. Secondary measures were the factors predicting baseline readiness to undertake ACP, and factors predicting postintervention ACP uptake in the intervention arm. Results At 6 months, formal ACP uptake was significantly higher (p<0.001) in the intervention arm (54/106, 51%), compared with usual care (6/43, 14%). ACP discussions with doctors were also significantly higher (p<0.005) in the intervention arm (76/106, 72%) compared with usual care (20/43, 47%). Those with a strong preference for the intervention were more likely to complete formal ACP documents than those randomly allocated. Increased symptom burden and preference for the intervention predicted later ACP uptake. Social support was positively associated with ACP discussion with loved ones, but negatively associated with discussion with doctors. Conclusions Nurse-led facilitated ACP is acceptable to patients with advanced respiratory disease and effective in increasing ACP discussions and completion

  9. 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.

  10. 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.

  11. Estimation of the epidemiological burden of human papillomavirus-related cancers and non-malignant diseases in men in Europe: a review

    PubMed Central

    2012-01-01

    Background The role of human papillomavirus (HPV) in malignant and non-malignant genital diseases in women is well known and the corresponding epidemiological burden has been widely described. However, less is known about the role of HPV in anal, penile and head and neck cancer, and the burden of malignant and non-malignant HPV-related diseases in men. The objective of this review is to estimate the epidemiological burden of HPV-related cancers and non-malignant diseases in men in Europe. Methods The annual number of new HPV-related cancers in men in Europe was estimated using Eurostat population data and applying cancer incidence rates published by the International Agency for Research on Cancer. The number of cancer cases attributable to HPV, and specifically to HPV16/18, was calculated based on the most relevant prevalence estimates. The annual number of new cases of genital warts was calculated from the most robust European studies; and latest HPV6/11 prevalence estimates were then applied. A literature review was also performed to retrieve exhaustive data on HPV infection at all anatomical sites under study, as well as incidence and prevalence of external genital warts, recurrent respiratory papillomatosis and HPV-related cancer trends in men in Europe. Results A total of 72, 694 new cancer cases at HPV-related anatomical sites were estimated to occur each year in men in Europe. 17,403 of these cancer cases could be attributable to HPV, with 15,497 of them specifically attributable to HPV16/18. In addition, between 286,682 and 325,722 new cases of genital warts attributable to HPV6/11were estimated to occur annually in men in Europe. Conclusions The overall estimated epidemiological burden of HPV-related cancers and non-malignant diseases is high in men in Europe. Approximately 30% of all new cancer cases attributable to HPV16/18 that occur yearly in Europe were estimated to occur in men. As in women, the vast majority of HPV-positive cancer in men is related

  12. Second allogeneic transplantation for relapse of malignant disease: retrospective analysis of outcome and predictive factors by the EBMT.

    PubMed

    Ruutu, T; de Wreede, L C; van Biezen, A; Brand, R; Mohty, M; Dreger, P; Duarte, R; Peters, C; Garderet, L; Schönland, S; Gratwohl, A; Niederwieser, D; de Witte, T; Kröger, N

    2015-12-01

    In patients treated with allogeneic stem cell transplantation (SCT) for malignant disease who suffer from a relapse after the transplantation, the role of second allogeneic SCT is often uncertain. In a retrospective analysis, 2632 second allogeneic transplantations carried out for a relapse after the first transplantation were analyzed to define indications and identify predictive factors. Fifteen percent of the patients remained relapse-free until 5 years after the second SCT. Patients with CML had a better survival than patients with other diseases. In a multivariate analysis, factors associated with better survival were low disease burden, longer remission duration after the first transplantation, longer interval between the transplantations, younger age, absence of grade II-IV acute GvHD or chronic GvHD after the first transplantation, and later year of transplantation. The European Society for Blood and Marrow Transplantation risk score predicted the outcome. Using the same donor as in the first transplantation vs another donor had no predictive value for survival. Sibling donor was a favorable predictive factor. In conclusion, second allogeneic SCT offers a reasonable option especially for young patients with a long remission after the first transplantation and a low disease burden. The present findings do not support the usefulness of changing the donor for the second transplantation.

  13. 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.

  14. 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

  15. Advances in Chagas disease drug development: 2009-2010

    PubMed Central

    Buckner, Frederick S.; Navabi, Nazlee

    2013-01-01

    Purpose of Review The need for better drugs to treat patients with Chagas disease remains urgent. This review summarizes the advancements in drug development over the past two years. Recent Findings Drug development efforts are almost exclusively occurring as preclinical research. The exceptions being Phase I safety studies for the cruzain inhibitor, K-777, and potential Phase II studies for the antifungal drug, posaconazole, and a prodrug of ravuconazole. Several recent laboratory investigations demonstrate anti-T. cruzi activity of novel small molecules in animal models. These include nonpeptidic cruzain inhibitors, novel inhibitors of the sterol 14α-demethylase enzyme, new compounds (arylimidamides) related to pentamidine, derivatives of nifurtimox, compounds using ruthenium complexes, and several natural products. The recent implementation of a high-throughput screen of >300,000 compounds against intracellular T. cruzi amastigotes done at the Broad Institute is an important development, yielding ~300 selective inhibitors, many of which may serve as leads for medicinal chemistry efforts. Summary Progress is slow, but recent advancements in both drug development and advocacy for research on neglected diseases are encouraging. Efforts to define a target product profile and to harmonize methodologies for testing drugs for Chagas disease are described herein. PMID:20885320

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

    PubMed

    Gasper, D; Barr, B; Li, H; Taus, N; Peterson, R; Benjamin, G; Hunt, T; Pesavento, P A

    2012-05-01

    A private zoological facility experienced an outbreak of malignant catarrhal fever (MCF) in 3 bongo antelope (Tragelaphus eurycerus). All cases were periparturient bongos that presented acutely anorectic beginning ~6 weeks after being housed with a Nubian ibex. Disease quickly progressed to respiratory distress and death within 24-72 hours of onset of clinical signs. Consistent gross findings in affected bongos were pulmonary edema and small pale tan foci in the livers. Histological lesions included a nonsuppurative vasculitis in multiple tissues, which is well recognized in MCF, but additionally included necrotizing cholangiohepatitis and neutrophilic, necrotizing myocarditis. Ibex-associated viral DNA was detected by polymerase chain reaction and was identical in sequence whether derived from bongos or ibex. The sequence closely matched an MCF viral DNA fragment that had been amplified from an ibex and bongo in a previous case report.

  17. 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

  18. 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

  19. Recent advances in the medical treatment of Cushing's disease.

    PubMed

    Fleseriu, Maria

    2014-01-01

    Cushing's disease is a condition of hypercortisolism caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. While rare, it is associated with significant morbidity and mortality, which suggests that early and aggressive intervention is required. The primary, definitive therapy for patients with Cushing's disease in the majority of patients is pituitary surgery, generally performed via a transsphenoidal approach. However, many patients will not achieve remission or they will have recurrences. The consequences of persistent hypercortisolism are severe and, as such, early identification of those patients at risk of treatment failure is exigent. Medical management of Cushing's disease patients plays an important role in achieving long-term remission after failed transsphenoidal surgery, while awaiting effects of radiation or before surgery to decrease the hypercortisolemia and potentially reducing perioperative complications and improving outcome. Medical therapies include centrally acting agents, adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers. Furthermore, several new agents are in clinical trials. To normalize the devastating disease effects of hypercortisolemia, it is paramount that successful patient disease management includes individualized, multidisciplinary care, with close collaboration between endocrinologists, neurosurgeons, radiation oncologists, and general surgeons. This commentary will focus on recent advances in the medical treatment of Cushing's, with a focus on newly approved ACTH modulators and glucocorticoid receptor blockers.

  20. ErbB Proteins as Molecular Target of Dietary Phytochemicals in Malignant Diseases

    PubMed Central

    Filippi, Alexandru; Ciolac, Oana-Alina

    2017-01-01

    ErbB proteins overexpression, in both normal and mutated forms, is associated with invasive forms of cancer prone to metastasis and with stronger antiapoptotic mechanisms and therefore more challenging to treat. Downstream effectors of ErbB receptors mediating these phenotypic traits include MAPK, STAT, and PI3K/AKT/mTOR pathways. Various phytochemical compounds were studied for their large number of biological effects including anticancer activity. Among these compounds, epigallocatechin-3-gallate (EGCG), the main catechin from green tea leaves, and curcumin, component of the curry powder, constituted the object of numerous studies. Both compounds were shown to act directly either on ErbB expression, or on their downstream signaling molecules. In this paper we aim to review the involvement of ErbB proteins in cancer as well as the biologic activity of EGCG and curcumin in ErbB expressing and overexpressing malignancies. The problems arising in the administration of the two compounds due to their reduced bioavailability when orally administered, as well as the progress made in this field, from using novel formulations to improved dosing regimens or improved synthetic analogs, are also discussed. PMID:28286519

  1. 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.

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

    PubMed

    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; Mistry, Pramod K

    2012-05-17

    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.

  3. Recent advances in treating Parkinson’s disease

    PubMed Central

    Oertel, Wolfgang H.

    2017-01-01

    This article summarizes (1) the recent achievements to further improve symptomatic therapy of motor Parkinson’s disease (PD) symptoms, (2) the still-few attempts to systematically search for symptomatic therapy of non-motor symptoms in PD, and (3) the advances in the development and clinical testing of compounds which promise to offer disease modification in already-manifest PD. However, prevention (that is, slowing or stopping PD in a prodromal stage) is still a dream and one reason for this is that we have no consensus on primary endpoints for clinical trials which reflect the progression in prodromal stages of PD, such as in rapid eye movement sleep behavior disorder (RBD) —a methodological challenge to be met in the future. PMID:28357055

  4. [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.

  5. 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.

  6. Progress in oncolytic virotherapy for the treatment of thyroid malignant neoplasm.

    PubMed

    Guan, Mingxu; Romano, Gaetano; Coroniti, Roberta; Henderson, Earl E

    2014-11-01

    Thyroid malignant neoplasm develops from follicular or parafollicular thyroid cells. A higher proportion of anaplastic thyroid cancer has an adverse prognosis. New drugs are being used in clinical treatment. However, for advanced thyroid malignant neoplasm such as anaplastic thyroid carcinoma, the major impediment to successful control of the disease is the absence of effective therapies. Oncolytic virotherapy has significantly progressed as therapeutics in recent years. The advance is that oncolytic viruses can be designed with biological specificity to infect, replicate and lyse tumor cells. Significant advances in virotherapy have being achieved to improve the accessibility, safety and efficacy of the treatment. Therefore, it is necessary to summarize and bring together the main areas covered by these investigations for the virotherapy of thyroid malignant neoplasm. We provide an overview of the progress in virotherapy research and clinical trials, which employ virotherapy for thyroid malignant neoplasm as well as the future prospect for virotherapy of thyroid malignant neoplasms.

  7. [Device-aided therapies in advanced Parkinson's disease].

    PubMed

    Timofeeva, A A

    2016-01-01

    Advanced stages of Parkinson's disease (PD) is a consequence of the severe neurodegenerative process and are characterized by the development of motor fluctuations and dyskinesia, aggravation of non-motor symptoms. Treatment with peroral and transdermal drugs can't provide an adequate control of PD symptoms and quality-of-life of the patients at this stage of disease. Currently, three device-aided therapies: deep brain stimulation (DBS), intrajejunal infusion of duodopa, subcutaneous infusion of apomorphine can be used in treatment of patients with advanced stages of PD. Timely administration of device-aided therapies and right choice of the method determine, to a large extent, the efficacy and safety of their use. Despite the high efficacy of all three methods with respect to the fluctuation of separate symptoms, each method has its own peculiarities. The authors reviewed the data on the expediency of using each method according to the severity of motor and non-motor symptoms, patient's age, PD duration, concomitant pathology and social support of the patients.

  8. Advances in vaccine research against economically important viral diseases of food animals: Infectious bursal disease virus.

    PubMed

    Jackwood, Daral J

    2016-11-22

    Numerous reviews have been published on infectious bursal disease (IBD) and infectious bursal disease virus (IBDV). Many high quality vaccines are commercially available for the control of IBD that, when used correctly, provide solid protection against infection and disease caused by IBDV. Viruses are not static however; they continue to evolve and vaccines need to keep pace with them. The evolution of IBDV has resulted in very virulent strains and new antigenic types of the virus. This review will discuss some of the limitations associated with existing vaccines, potential solutions to these problems and advances in new vaccines for the control of IBD.

  9. 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.

  10. 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...

  11. 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

  12. Cat scratch disease simulating a malignant process of the chest wall with coexistent osteomyelitis.

    PubMed

    Sakellaris, G; Kampitakis, E; Karamitopoulou, E; Scoulica, E; Psaroulaki, A; Mihailidou, E; Charissis, G

    2003-01-01

    A 6-y-old girl developed fever, soft-tissue mass in the right chest wall, osteomyelitis of the 10th rib and hepatic granuloma. Cat scratch disease was diagnosed by histological examination of the mass and serological tests. The patient was treated successfully with antibiotics and recovered completely, as shown by a 10 month follow-up.

  13. Advances in the assessment of disease activity in inflammatory bowel disease

    SciTech Connect

    Camilleri, M.; Proano, M. )

    1989-07-01

    Knowledge of the severity and extent of the inflammation in inflammatory bowel diseases provides a means of determining rational therapeutic strategies in affected patients. During the past 3 decades, several clinical, laboratory, and combined indices have been proposed for the assessment of inflammatory bowel disease; refinements in radiologic methods and the availability of endoscopy and biopsy have facilitated the accurate assessment of the extent and severity of the disease. In relapsing conditions such as inflammatory bowel disease, however, the use of such procedures is limited by the radiation exposure or the relatively invasive nature of the technique. In this article, we review the proposed methods and recent advances in assessment of patients with inflammatory bowel disease; we also discuss possible strategies at the time of diagnosis, during recurrence, and in evaluation of the efficacy of drug or dietic therapy. 58 references.

  14. Non-Malignant Respiratory Disease Among Workers in Industries Using Styrene—A Review of the Evidence

    PubMed Central

    Nett, Randall J.; Cox-Ganser, Jean M.; Hubbs, Ann F.; Ruder, Avima M.; Cummings, Kristin J.; Huang, Yuh-Chin T.; Kreiss, Kathleen

    2017-01-01

    Background Asthma and obliterative bronchiolitis (OB) cases have occurred among styrene-exposed workers. We aimed to investigate styrene as a risk factor for non-malignant respiratory disease (NMRD). Methods From a literature review, we identified case reports and assessed cross-sectional and mortality studies for strength of evidence of positive association (i.e., strong, intermediate, suggestive, none) between styrene exposure and NMRD-related morbidity and mortality. Results We analyzed 55 articles and two unpublished case reports. Ten OB cases and eight asthma cases were identified. Six (75%) asthma cases had abnormal styrene inhalation challenges. Thirteen (87%) of 15 cross-sectional studies and 12 (50%) of 24 mortality studies provided at least suggestive evidence that styrene was associated with NMRD-related morbidity or mortality. Six (66%) of nine mortality studies assessing chronic obstructive pulmonary disease-related mortality indicated excess mortality. Conclusions Available evidence suggests styrene exposure is a potential risk factor for NMRD. Additional studies of styrene-exposed workers are warranted. PMID:28079275

  15. Non-malignant respiratory diseases and occupational exposure to wood dust. Part I. Fresh wood and mixed wood industry.

    PubMed

    Jacobsen, Gitte; Schaumburg, Inger; Sigsgaard, Torben; Schlunssen, Vivi

    2010-01-01

    This paper reviews associations in literature between exposure to wood dust from fresh wood and non-malignant respiratory diseases. Criteria for inclusion are epidemiological studies in English language journals with an internal or external control group describing relationships between wood dust exposure and respiratory diseases or symptoms. The papers took into account smoking, and when dealing with lung function took age into consideration. A total of 25 papers concerning exposure to fresh wood and mixed wood formed the basis of this review. The results support an association between fresh wood dust exposure and asthma, asthma symptoms, coughing, bronchitis, and acute and chronic impairment of lung function. In addition, an association between fresh wood dust exposure and rhino-conjunctivitis was seen across studies. Apart from plicatic acid in western red cedar wood, no causal agent was consistently disclosed. Type 1 allergy is not suspected of being a major cause of wood dust induced asthma. Concurrent exposure to microorganisms and terpenes probably add to the inherent risk of wood dust exposure in the fresh wood industry.

  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. Malignant pleural effusion: medical approaches for diagnosis and management.

    PubMed

    Nam, Hae-Seong

    2014-05-01

    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.

  18. Childhood malignancy and maternal diabetes or other auto-immune disease during pregnancy.

    PubMed

    Westbom, L; Aberg, A; Källén, B

    2002-04-08

    Among 4380 children born in 1987-1997 of women with a diagnosis of diabetes and alive at the age of one, 10 were registered in the Swedish Cancer Registry before the end of 1998. The odds ratio for having a childhood cancer after maternal diabetes, stratified for year of birth, maternal age, parity, multiple birth, and 500 g birth weight class was 2.25 (95%CI 1.22-4.15). Among 5842 children born during the period 1973-1997 whose mothers had other auto-immune diseases (SLE, rheumatoid arthritis, Crohn, ulcerous colitis, multiple sclerosis or thyroiditis), the number of observed childhood cancers (9) was close to that expected (8.5). Maternal diabetes but not other auto-immune diseases may be a risk factor for childhood cancer.

  19. Total and lipid-bound serum sialic acid in benign and malignant breast disease.

    PubMed

    Romppanen, J; Eskelinen, M; Tikanoja, S; Mononen, I

    1997-01-01

    Elevation in the total sialic acid (TSA), TSA/total protein (TSA/TP) and lipid-bound sialic acid (LASA) concentration in serum occurs in breast cancer and we have studied the applicability of the assays in classification of undefined breast tumors. Sialic acid was determined by HPLC and the statistical evaluation included the receiver operating characteristic (ROC) and Youden's index analyses. In cancer patients, the serum LASA and TSA concentration was significantly higher (p < 0.05) than in patients with benign breast disease and all the markers were significantly higher (p < 0.0001) than in normal controls. All the markers had a low accuracy (AUCs < 0.75) in differentiating between breast cancer and benign breast disease and at the specificity level of 0.95 the corresponding sensitivities were 0.32 (TSA), 0.14 (TSA/TP) and 0.23 (LASA). The results indicate that both breast cancer and benign breast disease cause elevation of TSA, TSA/TP and LASA values in serum and do not provide reliable classification of undefined breast tumors.

  20. Advanced mast cell disease: an Italian Hematological Multicenter experience.

    PubMed

    Pagano, Livio; Valentini, Caterina Giovanna; Caira, Morena; Rondoni, Michela; Van Lint, Maria Teresa; Candoni, Anna; Allione, Bernardino; Cattaneo, Chiara; Marbello, Laura; Caramatti, Cecilia; Pogliani, Enrico Maria; Iannitto, Emilio; Giona, Fiorina; Ferrara, Felicetto; Invernizzi, Rosangela; Fanci, Rosa; Lunghi, Monia; Fianchi, Luana; Sanpaolo, Grazia; Stefani, Pietro Maria; Pulsoni, Alessandro; Martinelli, Giovanni; Leone, Giuseppe; Musto, Pellegrino

    2008-12-01

    The aim of the study is to evaluate clinical features, treatments and outcome of patients with systemic mast cell disease (MCD) who arrived to the attention of hematologists. A retrospective study was conducted over 1995-2006 in patients admitted in 18 Italian hematological divisions. Twenty-four cases of advanced MCD were collected: 12 aggressive SM (50%), 8 mast cell leukemia (33%), 4 SM with associated clonal non-mast cell-lineage hematologic disease (17%). Spleen and liver were the principal extramedullary organ involved. The c-kit point mutation D816V was found in 13/18 patients in which molecular biology studies were performed (72%). Treatments were very heterogeneous: on the whole Imatinib was administered in 17 patients, alpha-Interferon in 8, 2-CdA in 3; 2 patients underwent allogeneic hematopoietic stem cell transplantation. The overall response rate to Imatinib, the most frequently employed drugs, was of 29%, registering one complete remission and four partial remission; all responsive patients did not present D816V c-kit mutation. Overall three patients (12%) died for progression of disease. We conclude that MCD is characterized by severe mediator-related symptoms but with a moderate mortality rate. D816V c-kit mutation is frequent and associated with resistance against Imatinib. Because of the rarity of these forms, an effective standard of care is lacking. More data are needed to find new and successful therapeutic strategies.

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

    PubMed Central

    SUN, RONGRONG; LI, XIANCHI; LIU, MIN; ZENG, YI; CHEN, SHUANG; ZHANG, PEYING

    2016-01-01

    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. PMID:27220939

  2. 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

  3. Advances in Nanotechnology for the Management of Coronary Artery Disease

    PubMed Central

    Rhee, June-Wha; Wu, Joseph C.

    2013-01-01

    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. PMID:23245913

  4. Nursing staff's understanding expressions of people with advanced dementia disease.

    PubMed

    Eggers, Thomas; Ekman, Sirkka-Liisa; Norberg, Astrid

    2013-01-01

    People with advanced dementia disease (ADD) are known to have communication difficulties and thus it presents a challenge in understanding the expressions of these people. Because successful communication presupposes cooperation at least between 2 individuals, both individual's actions must be acknowledged. The aim of this study is to describe nursing staff's ways of understanding the expressions of people with ADD when communicating with them. Interviews from 8 nursing staff were analyzed using qualitative content analysis. Two themes were constructed: "Being in communication" and "Doing communication." Being in communication means that nursing staff perceive people with ADD as being capable of communication. Doing communication means that nursing staff attempt different individualized strategies to understand what people with ADD communicate. Good care of people with ADD presupposes nursing staff that are willing and able to relate to other people and to maintain good care for people with ADD continuous education and supervision are needed.

  5. 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.

  6. CAP—advancing the evaluation of preclinical Alzheimer disease treatments

    PubMed Central

    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. PMID:26416539

  7. Advances in the genetic mechanisms of mitochondrial disease.

    PubMed

    Vladutiu, G D

    1997-12-01

    During the past 16 years since the delineation of the human mitochondrial genome, substantial advances have been made in identifying pathogenic mutations causing mitochondrial disorders. However, just as we have come to accept the unexpected in the nontraditional aspects of Mendelian inheritance with the discovery of trinucleotide expansions, imprinting and uniparental disomy, unusual characteristics of mitochondrial inheritance also have been found that defy existing laws. For example, we now know that the nuclear genetic background of an individual might influence the expression and tissue specificity of mitochondrial mutations. Pathogenic mitochondrial DNA mutations contribute to the generation of new mutations by compromising mitochondrial function and increasing free radical production. Evidence for recombination raises new questions about repair mechanisms of mitochondrial DNA. It appears that the more we learn about the bases of mitochondrial disease, the more complex diagnosis, treatment, and genetic counseling become.

  8. 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

  9. A novel mouse model of advanced diabetic kidney disease.

    PubMed

    Thibodeau, Jean-Francois; Holterman, Chet E; Burger, Dylan; Read, Naomi C; Reudelhuber, Timothy L; Kennedy, Christopher R J

    2014-01-01

    Currently available rodent models exhibit characteristics of early diabetic nephropathy (DN) such as hyperfiltration, mesangial expansion, and albuminuria yet features of late DN (hypertension, GFR decline, tubulointerstitial fibrosis) are absent or require a significant time investment for full phenotype development. Accordingly, the aim of the present study was to develop a mouse model of advanced DN with hypertension superimposed (HD mice). Mice transgenic for human renin cDNA under the control of the transthyretin promoter (TTRhRen) were employed as a model of angiotensin-dependent hypertension. Diabetes was induced in TTRhRen mice through low dose streptozotocin (HD-STZ mice) or by intercrossing with OVE26 diabetic mice (HD-OVE mice). Both HD-STZ and HD-OVE mice displayed more pronounced increases in urinary albumin levels as compared with their diabetic littermates. Additionally, HD mice displayed renal hypertrophy, advanced glomerular scarring and evidence of tubulointerstitial fibrosis. Both HD-OVE and HD-STZ mice showed evidence of GFR decline as FITC-inulin clearance was decreased compared to hyperfiltering STZ and OVE mice. Taken together our results suggest that HD mice represent a robust model of type I DN that recapitulates key features of human disease which may be significant in studying the pathogenesis of DN and in the assessment of putative therapeutics.

  10. Advanced glycation end products contribute to amyloidosis in Alzheimer disease.

    PubMed Central

    Vitek, M P; Bhattacharya, K; Glendening, J M; Stopa, E; Vlassara, H; Bucala, R; Manogue, K; Cerami, A

    1994-01-01

    Alzheimer disease (AD) is characterized by deposits of an aggregated 42-amino-acid beta-amyloid peptide (beta AP) in the brain and cerebrovasculature. After a concentration-dependent lag period during in vitro incubations, soluble preparations of synthetic beta AP slowly form fibrillar aggregates that resemble natural amyloid and are measurable by sedimentation and thioflavin T-based fluorescence. Aggregation of soluble beta AP in these in vitro assays is enhanced by addition of small amounts of pre-aggregated beta-amyloid "seed" material. We also have prepared these seeds by using a naturally occurring reaction between glucose and protein amino groups resulting in the formation of advanced "glycosylation" end products (AGEs) which chemically crosslink proteins. AGE-modified beta AP-nucleation seeds further accelerated aggregation of soluble beta AP compared to non-modified "seed" material. Over time, nonenzymatic advanced glycation also results in the gradual accumulation of a set of posttranslational covalent adducts on long-lived proteins in vivo. In a standardized competitive ELISA, plaque fractions of AD brains were found to contain about 3-fold more AGE adducts per mg of protein than preparations from healthy, age-matched controls. These results suggest that the in vivo half-life of beta-amyloid is prolonged in AD, resulting in greater accumulation of AGE modifications which in turn may act to promote accumulation of additional amyloid. PMID:8197133

  11. Advances in designs for Alzheimer's disease clinical trials.

    PubMed

    Cummings, Jeffrey; Gould, Heath; Zhong, Kate

    2012-01-01

    There is an urgent need to identify new treatments for the rapidly growing population of people with Alzheimer's disease (AD). Innovations in clinical trial designs many help to reduce development time, provide more definitive answers regarding drug efficacy, and facilitate prioritizing compounds to be advanced to Phase III clinical trials. Standard designs compare drug and placebo changes from baseline on a rating scale. Baysian adaptive clinical trials allow the use of data collected in the trial to modify doses, sample size, trial duration, and entry criteria in an ongoing way as the data are collected. Disease-modification is supported by findings on staggered start and delayed withdrawal designs. Futility designs can use historical controls and may shorten trial duration. Combination therapy designs may allow investigation of additive or synergistic treatment effects. Novel trial selection criteria allow investigation of treatment effects in asymptomatic or minimally symptomatic, prodromal AD populations. The Clinical Dementia Rating-Sum of Boxes (CDR-SOB) can be considered as a single trial outcome in early disease populations. Alternate forms of the Alzheimer's Disease Assessment Scale-Cognitive Portion (ADAS-cog), computerized measures, and pharmacoeconomic scales provide new and relevant information on drug effects. Comparative dose strategies are used in trials of symptomatic agents, and novel methods including withdrawal designs, symptom emergence analyses, and sequential designs are being utilized to assess the efficacy of putative psychotropic agents. The choice of trial design is driven by the question to be answered by the clinical trial; an increasing number of design approaches are available and may be useful in accelerating and refining AD drug development.

  12. Advances in designs for Alzheimer’s disease clinical trials

    PubMed Central

    Cummings, Jeffrey; Gould, Heath; Zhong, Kate

    2012-01-01

    There is an urgent need to identify new treatments for the rapidly growing population of people with Alzheimer’s disease (AD). Innovations in clinical trial designs many help to reduce development time, provide more definitive answers regarding drug efficacy, and facilitate prioritizing compounds to be advanced to Phase III clinical trials. Standard designs compare drug and placebo changes from baseline on a rating scale. Baysian adaptive clinical trials allow the use of data collected in the trial to modify doses, sample size, trial duration, and entry criteria in an ongoing way as the data are collected. Disease-modification is supported by findings on staggered start and delayed withdrawal designs. Futility designs can use historical controls and may shorten trial duration. Combination therapy designs may allow investigation of additive or synergistic treatment effects. Novel trial selection criteria allow investigation of treatment effects in asymptomatic or minimally symptomatic, prodromal AD populations. The Clinical Dementia Rating-Sum of Boxes (CDR-SOB) can be considered as a single trial outcome in early disease populations. Alternate forms of the Alzheimer’s Disease Assessment Scale-Cognitive Portion (ADAS-cog), computerized measures, and pharmacoeconomic scales provide new and relevant information on drug effects. Comparative dose strategies are used in trials of symptomatic agents, and novel methods including withdrawal designs, symptom emergence analyses, and sequential designs are being utilized to assess the efficacy of putative psychotropic agents. The choice of trial design is driven by the question to be answered by the clinical trial; an increasing number of design approaches are available and may be useful in accelerating and refining AD drug development. PMID:23383393

  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. Skin: A mirror of internal malignancy

    PubMed Central

    Vora, Rita V.; Kota, RahulKrishna S.; Diwan, Nilofar G.; Jivani, Nidhi B.; Gandhi, Shailee S.

    2016-01-01

    Skin manifestations are a reflection of many of the internal diseases. Sometimes, skin disease may be the only manifestation of the internal disease. Internal malignancies may give rise to a number of cutaneous manifestations through their immunological, metabolic, and metastatic consequences. Curth proposed criteria to establish a causal relationship between a dermatosis and a malignant internal disease. Malignancy can present with a plethora of cutaneous manifestations. Here, we describe in brief about various skin manifestations of internal malignancies. PMID:28144085

  15. Drosophila models of Alzheimer's disease: advances, limits, and perspectives.

    PubMed

    Bouleau, Sylvina; Tricoire, Hervé

    2015-01-01

    Amyloid-β protein precursor (AβPP) and the microtubule-associated protein tau (MAPT) are the two key players involved in Alzheimer's disease (AD) and are associated with amyloid plaques and neurofibrillary tangles respectively, two key hallmarks of the disease. Besides vertebrate models, Drosophila models have been widely used to understand the complex events leading to AD in relation to aging. Drosophila benefits from the low redundancy of the genome which greatly simplifies the analysis of single gene disruption, sophisticated molecular genetic tools, and reduced cost compared to mammals. The aim of this review is to describe the recent advances in modeling AD using fly and to emphasize some limits of these models. Genetic studies in Drosophila have revealed some key aspects of the normal function of Appl and Tau, the fly homologues of AβPP and MAPT that may be disrupted during AD. Drosophila models have also been useful to uncover or validate several pathological pathways or susceptibility genes, and have been readily implemented in drug screening pipelines. We discuss some limitations of the current models that may arise from differences in structure of Appl and Tau compared to their human counterparts or from missing AβPP or MAPT protein interactors in flies. The advent of new genome modification technologies should allow the development of more realistic fly models and to better understand the relationship between AD and aging, taking advantage of the fly's short lifespan.

  16. Recent Advances in Conjugated Polymer Materials for Disease Diagnosis.

    PubMed

    Lv, Fengting; Qiu, Tian; Liu, Libing; Ying, Jianming; Wang, Shu

    2016-02-10

    The extraordinary optical amplification and light-harvesting properties of conjugated polymers impart sensing systems with higher sensitivity, which meets the primary demands of early cancer diagnosis. Recent advances in the detection of DNA methylation and mutation with polyfluorene derivatives based fluorescence resonance energy transfer (FRET) as a means to modulate fluorescent responses attest to the great promise of conjugated polymers as powerful tools for the clinical diagnosis of diseases. To facilitate the ever-changing needs of diagnosis, the development of detection approaches and FRET signal analysis are highlighted in this review. Due to their exceptional brightness, excellent photostability, and low or absent toxicity, conjugated polymers are verified as superior materials for in-vivo imaging, and provide feasibility for future clinical molecular-imaging applications. The integration of conjugated polymers with clinical research has shown profound effects on diagnosis for the early detection of disease-related biomarkers, as well as in-vivo imaging, which leads to a multidisciplinary scientific field with perspectives in both basic research and application issues.

  17. Pelvic inflammatory disease increases the risk of a second primary malignancy in patients with cervical cancer treated by surgery alone.

    PubMed

    Chiou, Wen-Yen; Chen, Chien-An; Lee, Moon-Sing; Lin, Hon-Yi; Li, Chung-Yi; Su, Yu-Chieh; Tsai, Shiang-Jiun; Hung, Shih-Kai

    2016-11-01

    As the number of long-term cervical cancer survivors continues to increase because of improvements in treatment, concerns about second primary malignancy have grown. The high-risk area of second primary cancers in cervical cancer survivors is the pelvis. Pelvic inflammatory disease (PID) could be a useful marker for gynecological cancers. Thus, we designed a large-scale, nationwide, controlled cohort study to investigate whether PID or other risk factors increased the risk of second primary cancers in patients with cervical cancer treated by surgery alone.Between 2000 and 2010, a total of 24,444 cervical cancer patients were identified using the Registry Data for Catastrophic Illness and the National Health Insurance Research Database (NHIRD) of Taiwan. Patients who received definite surgery were selected. To exclude the effect on second primary malignancy by treatment modalities, all cervical patients who ever having received adjuvant or definite radiotherapy or chemotherapy for primary cervical cancer were excluded. Finally, 3860 cervical cancer patients treated by surgery alone without adjuvant treatments were analyzed.Cox proportional hazards model was used for multivariate analysis and the Kaplan-Meier method was used to assess the cumulative risks. Regarding the incidence of second primary cancers, the standardized incidence ratio (SIR) was used.The median follow-up time was 56.6 months. The 6-year cumulative risk of second primary cancers is 0.16% and 0.12% for PID and without PID, respectively. After adjustment for confounders, age of less than 50 years, the presence of diabetes mellitus, and PID were significantly positivity associated with the risk of second primary cancers. The hazard ratios (HRs) of age less than 50 years, diabetes mellitus, and PID were 1.38 (95% CI = 1.11-2.04), 1.40 (95% CI = 1.06-1.85), and 1.35 (95% CI = 1.00-1.81), respectively. A higher incidence of second primary cancers was observed in the genitals, bladder, and

  18. Phase I clinical and pharmacokinetic study of oral penclomedine (NSC 338720) in adults with advanced solid malignancy.

    PubMed

    Liu, Glenn; Berlin, Jordan; Tutsch, Kendra D; Van Ummersen, Lynn; Dresen, Amy; Marnocha, Rebecca; Arzomanian, Rhoda; Alberti, Dona; Feierabend, Chris; Binger, Kimberly; Wilding, George

    2002-03-01

    Penclomedine is a synthetic alpha-picoline derivative that has shown antitumor activity both in preclinical development and in Phase I work using an i.v. preparation. The main toxicities seen in those studies were dose dependent and mainly neurocerebellar, with hematological toxicity being far less severe. This Phase I trial of p.o. penclomedine was conducted to potentially alter the toxicity profile and to avoid the neurological side effects seen with i.v. penclomedine. Eligibility criteria included microscopic confirmation of a solid malignancy or lymphoma with a lack of effective anticancer therapy. Twenty patients were enrolled. The median age was 60.5 years, and the median performance status was one. All but one patient had received prior systemic therapy. The starting dose of penclomedine was 200 mg/m(2) p.o. for 5 days, and was escalated according to a traditional Fibonacci sequence until the maximum tolerated dose (MTD) was observed. No treatment-related deaths were observed during the study. The MTD was determined to be 800 mg/m(2) p.o. for 5 days. Dose-limiting toxicities included mainly neurocerebellar symptoms such as ataxia and dysmetria, but neurocortical symptoms, such as confusion, were seen as well. Myelosuppression was less common and resulted in the discontinuation of therapy in only two patients. Pharmacokinetics show that the observed MTD is consistent with the i.v. preparations, and that the bioavailability of p.o. penclomedine is 49 +/- 18%. This regimen can be considered for additional studies in patients with intracranial neoplasms, because good central nervous system penetration is evident. Further development of penclomedine metabolites, such as 4-O-demethylpenclomedine, should be considered to minimize dose-limiting neurotoxicity.

  19. First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial

    PubMed Central

    Arrieta, Ó; Medina, L A; Estrada-Lobato, E; Hernández-Pedro, N; Villanueva-Rodríguez, G; Martínez-Barrera, L; Macedo, E O; López-Rodríguez, V; Motola-Kuba, D; Corona-Cruz, J F

    2012-01-01

    Background: Chemotherapy based on platinum is the standard treatment for unresectable malignant pleural mesothelioma (MPM). Liposomal doxorubicin (LD) consists of pegylated phospholipid vesicles that encapsulate doxorubicin-enhancing liposome deposition in the tumour. We evaluated the toxicity profile and anti-tumour activity of cisplatin plus LD in untreated patients with MPM, as well as 99mTc-LD distribution in MPM lesions after chemotherapy administration. Methods: A total of 38 patients with non-resectable MPM received LD 40 mg m−2 and cisplatin 60 mg m−2 every 21 days. Gamma camera images of 99mTc-LD were acquired to evaluate LD accumulation in measurable tumour tissue. The study was registered in Clinical Trials (NCT00886028). Results: In all, 72% of patients were stage III and 28% were stage IV. Eighty four percent and 16% have high and low risk acording EORTC respectively. The median time to progression was 4.6 months (95% confidence interval (95% CI: 3.4–5.9 months), and median overall survival (OS) was 19.6 months (15.2–37.2 months). Patients that responded to chemotherapy treatment had better survival than patients who did not. Functional physical scales, dysnea, cough, and chest/arm pain demonstrated improvement. The accumulation ratio of LD in tumour and soft tissues vs liver was 0.78±0.16 and 0.29±0.09, respectively. After 1 h of administration, LD uptake in tumour tissue was higher than in soft tissue (P< 0.001). Conclusion: The combination of LD and cisplatin results in an active therapeutic regimen for unresectable MPM, with an acceptable toxicity profile and improvement in quality of life. 99mTc-LD showed higher levels of tumour uptake as compared with surrounding tissues. PMID:22353806

  20. Pleural malignancies.

    PubMed

    Friedberg, Joseph S; Cengel, Keith A

    2010-07-01

    Pleural malignancies, primary or metastatic, portend a grim prognosis. In addition to the serious oncologic implications of a pleural malignancy, these tumors can be highly symptomatic. A malignant pleural effusion can cause dyspnea, secondary to lung compression, or even tension physiology from a hydrothorax under pressure. The need to palliate these effusions is a seemingly straightforward clinical scenario, but with nuances that can result in disastrous complications for the patient if not attended to appropriately. Solid pleural malignancies can cause great pain from chest wall invasion or can cause a myriad of morbid symptoms because of the invasion of thoracic structures, such as the heart, lungs, or esophagus. This article reviews pleural malignancies, the purely palliative treatments, and the treatments that are performed with definitive (curative) intent.

  1. Efficacy and safety of micafungin for treatment of serious Candida infections in patients with or without malignant disease.

    PubMed

    Cornely, Oliver A; Marty, Francisco M; Stucker, Flavie; Pappas, Peter G; Ullmann, Andrew J

    2011-11-01

    The aim of this study was to evaluate micafungin efficacy for treatment of invasive candidiasis/candidaemia in patients with cancer. Modified intent-to-treat populations were analysed from two trials: one, in adults and children with confirmed Candida infection, compared micafungin (adults 100 mg day(-1); children 2 mg kg(-1) day(-1)) with liposomal amphotericin B (L-AmB 3 mg kg(-1) day(-1)); and the other, in adults only, compared micafungin (100 or 150 mg day(-1)) with caspofungin (50 mg day(-1); 70 mg loading dose). Primary efficacy endpoint in both trials was treatment success, defined as both clinical and mycological response at end of therapy. In the micafungin/L-AmB trial, 183/489 patients had malignancy (37% neutropenic). In the micafungin/caspofungin trial, 176/572 patients had malignancy (26% neutropenic). Micafungin treatment success rates were generally similar in patients with/without malignancy and to rates observed with L-AmB and caspofungin. Most patients with malignancy and neutropenia were successfully treated by all three drugs. For all drugs, incidence of discontinuations because of treatment-related adverse events was similar for patients with malignancy (≤7.7%) vs. no malignancy (≤8.0%). These results suggest that compared with L-AmB and caspofungin, micafungin was effective and well tolerated in patients with candidiasis/candidaemia with/without malignancy. Further prospective trials are recommended to evaluate comparative outcomes with a primary focus on patients with malignancies and invasive candidiasis.

  2. 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.

  3. Allogeneic marrow transplantation following cyclophosphamide and escalating doses of hyperfractionated total body irradiation in patients with advanced lymphoid malignancies: A phase I/II trial

    SciTech Connect

    Demirer, T.; Petersen, F.B.; Appelbaum, F.R.

    1995-07-15

    The purpose of this investigation was to define the maximum tolerated dose (MTD) of unshielded total body irradiation (TBI) delivered from dual {sup 60}C sources at an exposure rate of 0.08 Gy/min and given in thrice daily fractions of 1.2 Gy in patients with advanced lymphoid malignancies. Forty-four patients with a median age of 28 (range 6-48) years were entered into a Phase I/II study. All patients received cyclophosphamide (Cy), 120 mg/kg administered over 2 days before TBI. Marrow from human leukocyte antigen (HLA) identical siblings was infused following the last dose of TBI. An escalation-deescalation schema designed to not exceed an incidence of 25% of Grade 3-4 regimen-related toxicities (RRTs) was used. The first dose level tested was 13.2 Gy followed by 14.4 Gy. None of the four patients at the dose level of 13.2 Gy developed Grade 3-4 RRT. Two of the first eight patients receiving 14.4 Gy developed Grade 3-4 RRT, establishing this as the MTD. An additional 32 patients were evaluated at the 14.4 Gy level to confirm these initial observations. Of 40 patients receiving 14.4 Gy, 13 (32.5%) developed Grade 3-4 RRTs; 46% in adults and 12% in children. The primary dose limiting toxicity was Grade 3-4 hepatic toxicity, which occurred in 12.5% of patients. Noninfectious Grade 3-4 interstitial pneumonia syndrome occurred in 5% of patients. The actuarial probabilities of event-free survival, relapse, and nonrelapse mortality at 2 years were 0.10, 0.81, and 0.47, respectively, for patients who received 14.4 Gy of TBI. The outcome for patients receiving 14.4 Gy of TBI was not different from previous studies of other CY and TBI regimens in patients with advanced lymphoid malignancies. These data showed that the incidence of Grade 3-4 RRTs in adults was greater than the 25% maximum set as the goal of this study, suggesting that 13.2 Gy is a more appropriate dose of TBI for adults, while 14.4 Gy is an appropriate dose for children. 36 refs., 1 fig., 3 tabs.

  4. Vemurafenib for the treatment of locally advanced or metastatic BRAF V600 mutation-positive malignant melanoma: a NICE single technology appraisal.

    PubMed

    Beale, Sophie; Dickson, Rumona; Bagust, Adrian; Blundell, Michaela; Dundar, Yenal; Boland, Angela; Marshall, Ernie; Plummer, Ruth; Proudlove, Chris

    2013-12-01

    Vemurafenib is an oral BRAF inhibitor licenced for the treatment of locally advanced or metastatic BRAF V600-mutation positive malignant melanoma. The manufacturer of vemurafenib, Roche Products Limited, was invited by the National Institute for Health and Care Excellence (NICE) to submit evidence of the drug's clinical- and cost-effectiveness for its licenced indication, to inform the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal. This article summarises the ERG's review of the evidence submitted by the manufacturer and also includes a summary of the NICE Appraisal Committee (AC) decision. The ERG reviewed the clinical- and cost-effectiveness evidence in accordance with the decision problem defined by NICE. The ERG's analysis of the submitted economic model assessed the appropriateness of the approach taken by the manufacturer in modelling the decision problem. It also included an assessment of the reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to impact substantially on the base-case cost-effectiveness results. The clinical evidence was derived from BRIM 3 (BRAF Inhibitor in Melanoma 3), a well-designed, multi-centre, multi-national, phase III, randomised controlled trial (RCT). Clinical outcome results from the October 2011 data cut showed that median overall survival for patients treated with vemurafenib was 13.2 months compared with 9.6 months for those treated with dacarbazine. The ERG's main concern with the trial was the potential for confounding because of the early introduction of the crossover from the comparator drug to vemurafenib or another BRAF inhibitor. The submitted incremental cost-effectiveness ratio (ICER

  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. An advanced case of indium lung disease with progressive emphysema

    PubMed Central

    Nakano, Makiko; Tanaka, Akiyo; Hirata, Miyuki; Kumazoe, Hiroyuki; Wakamatsu, Kentaro; Kamada, Dan; Omae, Kazuyuki

    2016-01-01

    Objectives: To report the occurrence of an advanced case of indium lung disease with severely progressive emphysema in an indium-exposed worker. Case report: A healthy 42-year-old male smoker was employed to primarily grind indium-tin oxide (ITO) target plates, exposing him to indium for 9 years (1998-2008). In 2004, an epidemiological study was conducted on indium-exposed workers at the factory in which he worked. The subject's serum indium concentration (In-S) was 99.7 μg/l, while his serum Krebs von den Lungen-6 level was 2,350 U/ml. Pulmonary function tests showed forced vital capacity (FVC) of 4.17 l (91.5% of the JRS predicted value), forced expiratory volume in 1 s (FEV1) of 3.19 l (80.8% of predicted), and an FEV1-to-FVC ratio of 76.5%. A high-resolution chest computed tomography (HRCT) scan showed mild interlobular septal thickening and mild emphysematous changes. In 2008, he was transferred from the ITO grinding workplace to an inspection work section, where indium concentrations in total dusts had a range of 0.001-0.002 mg/m3. In 2009, the subject's In-S had increased to 132.1 μg/l, and pulmonary function tests revealed obstructive changes. In addition, HRCT scan showed clear evidence of progressive lung destruction with accompanying severe centrilobular emphysema and interlobular septal thickening in both lung fields. The subject's condition gradually worsened, and in 2015, he was registered with the Japan Organ Transplant Network for lung transplantation (LTx). Conclusions: Heavy indium exposure is a risk factor for emphysema, which can lead to a severity level that requires LTx as the final therapeutic option. PMID:27488043

  7. Hypercalcemia of malignancy and new treatment options

    PubMed Central

    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

  8. Serum alpha-fetoprotein subfractions identified by Ricinus communis agglutinin I in hepatic malignancies, yolk sac tumor, benign hepatic diseases, and fetal stage.

    PubMed

    Ishiguro, T; Takahashi, Y

    1989-01-01

    Using Ricinus communis agglutinin I (RCA-I) affinity crossed-line immunoelectrophoresis, alpha-fetoprotein (AFP) subfractions were studied in sera from patients with primary hepatic cancer (PHC), hepatic metastasis of gastric cancer (HMGC), yolk sac tumor (YST), acute or chronic hepatitis or hepatic cirrhosis. Fetal AFP subfractions were also examined in amniotic fluids or in culture fluids of fetal tissues. RCA-I non-reactive subfraction was commonly found in PHC, HMGC, YST, benign hepatic diseases, and fetal stage. RCA-I weakly reactive (WR) or strongly reactive (SR) subfraction was noted only in malignant diseases. RCA-I has a specific affinity to terminal galactose in oligosaccharide, and the presence of sialic acid on galactose residue(s) inhibits the affinity with RCA-I. Therefore, common AFP subfraction non-reactive with RCA-I was assumed to be galactosialyl form, while RCA-I WR and SR subfractions found only in malignancies were monogalactosyl and digalactosyl, respectively. Clinically this approach to detect the RCA-I WR or SR subfraction facilitates a differential diagnosis of AFP-producing malignancies and benign conditions.

  9. Improvement with ongoing Enzyme Replacement Therapy in advanced late-onset Pompe disease: a case study.

    PubMed

    Case, Laura E; Koeberl, Dwight D; Young, Sarah P; Bali, Deeksha; DeArmey, Stephanie M; Mackey, Joanne; Kishnani, Priya S

    2008-12-01

    Benefits of enzyme replacement therapy with Myozyme (alglucosidase alfa), anecdotally reported in late-onset Pompe disease, range from motor and pulmonary improvement in less severely affected patients, to stabilization with minimal improvement in those with advanced disease. We report a case of a 63-year-old patient with significant morbidity who made notable motor and pulmonary function gains after two years on therapy. Thus, improvements in those with advanced disease may be possible after long-term treatment.

  10. Advanced Tracers in PET Imaging of Cardiovascular Disease

    PubMed Central

    Zhang, Wei; Wu, Hua; Liu, Gang

    2014-01-01

    Cardiovascular disease is the leading cause of death worldwide. Molecular imaging with targeted tracers by positron emission tomography (PET) allows for the noninvasive detection and characterization of biological changes at the molecular level, leading to earlier disease detection, objective monitoring of therapies, and better prognostication of cardiovascular diseases progression. Here we review, the current role of PET in cardiovascular disease, with emphasize on tracers developed for PET imaging of cardiovascular diseases. PMID:25389529

  11. Dexamethasone-induced recrudescence of malignant catarrhal fever and associated lymphosarcoma and granulomatous disease in a Formosan sika deer (Cervus nippon taiouanus).

    PubMed

    Heuschele, W P; Nielsen, N O; Oosterhuis, J E; Castro, A E

    1985-07-01

    Malignant catarrhal fever (MCF) was diagnosed in a 2-week-old Formosan sika deer. The fawn had been previously exposed to a clinically normal neonatal wildebeest calf from which alcelaphine herpesvirus-1 was isolated. Alcelaphine herpesvirus-1 was isolated from buffy coat leukocytes and nasal and ocular secretions of the fawn during the acute illness. The fawn clinically recovered after 3 weeks. Virus was not recovered from blood at this time. Dexamethasone, given 4 months after clinical recovery, resulted in reisolation of MCF virus from blood and recrudescence of clinical MCF. The deer was euthanatized. At necropsy, pathognomonic lesions of MCF, granulomatous disease, and malignant lymphoma were observed. Antibodies to bovine leukosis viral antigens were not detected in the serum. The epidemiologic and pathogenetic importance of the findings are discussed.

  12. Expression of RNA-binding motif 10 is associated with advanced tumor stage and malignant behaviors of lung adenocarcinoma cancer cells.

    PubMed

    Guan, Guofang; Li, Ranwei; Tang, Wenfang; Liu, Tiecheng; Su, Zhenzhong; Wang, Yan; Tan, Jingjin; Jiang, Shan; Wang, Ke

    2017-03-01

    This study assessed RNA-binding motif 10 expression in lung adenocarcinoma tissues and examined the role and mechanism of RNA-binding motif 10 in the regulation of lung adenocarcinoma malignancy. Lung adenocarcinoma and corresponding adjacent non-tumor lung tissues from 41 patients were subjected to reverse transcription-polymerase chain reaction and Western blot assessment to detect RNA-binding motif 10 expression. Recombinant lentivirus carrying RNA-binding motif 10 complementary DNA was used to infect lung adenocarcinoma cell lines, A549 and H1299 cells. Complementary DNA microarray was used to profile RNA-binding motif 10-regulated genes. Levels of RNA-binding motif 10 messenger RNA and protein were significantly lower in lung adenocarcinoma tissues than those in paired non-tumor tissues (p < 0.001). Reduced RNA-binding motif 10 expression was found to be associated with an advanced tumor stage. RNA-binding motif 10 overexpression inhibited viability and colony formation capacity of lung adenocarcinoma cell lines and induced cell-cycle arrest at G0/G1 phase in A549 cells and at S phase in H1299 cells. Complementary DNA microarray analysis identified 304 upregulated and 386 downregulated genes induced by RNA-binding motif 10 overexpression, which may be involved in cancer, focal adhesion, peroxisome proliferator-activated receptor-regulated gene pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase signaling, complement and coagulation cascades, platelet amyloid precursor protein pathway, extracellular matrix-receptor interaction, and small cell lung cancer-related genes. Expression of FGF2, EGFR, WNT5A, NF-κB, and RAP1A was downregulated, whereas expression of AKT2, BIRC3, and JUN was upregulated. RNA-binding motif 10 messenger RNA and protein were reduced in lung adenocarcinoma tissues, and RNA-binding motif 10 overexpression inhibited lung adenocarcinoma cancer cell malignant behavior in vitro. Molecularly, RNA-binding motif

  13. Genetics Home Reference: malignant hyperthermia

    MedlinePlus

    ... 26(5):413-25. Citation on PubMed Robinson R, Carpenter D, Shaw MA, Halsall J, Hopkins P. Mutations in RYR1 in malignant hyperthermia and central core disease. Hum Mutat. 2006 Oct;27(10):977-89. Review. Citation on PubMed Rosenberg H, Davis M, James D, Pollock N, Stowell K. Malignant ...

  14. Early malignant syphilis*

    PubMed Central

    Ortigosa, Yara Martins; Bendazzoli, Paulo Salomão; Barbosa, Angela Marques; Ortigosa, Luciena Cegatto Martins

    2016-01-01

    Early malignant syphilis is a rare and severe variant of secondary syphilis. It is clinically characterized by lesions, which can suppurate and be accompanied by systemic symptoms such as high fever, asthenia, myalgia, and torpor state. We report a diabetic patient with characteristic features of the disease showing favorable evolution of the lesions after appropriate treatment. PMID:28300925

  15. 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...

  16. Nutrition for Advanced Chronic Kidney Disease in Adults

    MedlinePlus

    ... peanut oil canola oil Why is knowing about sodium important for someone with advanced CKD? Too much ... who have high blood pressure. High- and Low-sodium Foods High-sodium Foods Low-sodium Alternatives Salt ...

  17. New MS Drug Shows 'Breakthrough' Promise for Advanced Disease

    MedlinePlus

    ... News) -- A new drug slows the progress of multiple sclerosis, including an advanced form of the degenerative nerve ... also proved superior in treating people with relapsing multiple sclerosis, the most common form of MS, compared with ...

  18. Recent Advances in Endometrial Cancer

    PubMed Central

    Tran, Arthur-Quan; Gehrig, Paola

    2017-01-01

    Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer. PMID:28184290

  19. Current advances on genetic resistance to rice blast disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice blast disease caused by the fungal pathogen Magnaporthe oryzae is one of the most threatening fungal diseases resulting in significant annual crop losses worldwide. Blast disease has been effectively managed by a combination of resistant (R) gene deployment, application of fungicides, and suita...

  20. 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

  1. 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

    2016-04-22

    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.

  2. 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.

  3. Advances in surveillance of periodontitis: the Centers for Disease Control and Prevention periodontal disease surveillance project.

    PubMed

    Eke, Paul I; Thornton-Evans, Gina; Dye, Bruce; Genco, Robert

    2012-11-01

    The Centers for Disease Control and Prevention (CDC) has as one of its strategic goals to support and improve surveillance of periodontal disease. In 2003, the CDC initiated the CDC Periodontal Disease Surveillance Project in collaboration with the American Academy of Periodontology to address population-based surveillance of periodontal disease at the local, state, and national levels. This initiative has made significant advancements toward the goal of improved surveillance, including developing valid self-reported measures that can be obtained from interview-based surveys to predict prevalence of periodontitis in populations. This will allow surveillance of periodontitis at the state and local levels and in countries where clinical resources for surveillance are scarce. This work has produced standard case definitions for surveillance of periodontitis that are now widely recognized and applied in population studies and research. At the national level, this initiative has evaluated the validity of previous clinical examination protocols and tested new protocols on the National Health and Nutrition Examination Survey (NHANES), recommending and supporting funding for the gold-standard full-mouth periodontal examination in NHANES 2009 to 2012. These examinations will generate accurate estimates of the prevalence of periodontitis in the US adult population and provide a superior dataset for surveillance and research. Also, this data will be used to generate the necessary coefficients for our self-report questions for use in subsets of the total US population. The impact of these findings on population-based surveillance of periodontitis and future directions of the project are discussed along with plans for dissemination and translation efforts for broader public health use.

  4. Giant malignant insulinoma

    PubMed Central

    Karavias, Dimitrios; Habeos, Ioannis; Maroulis, Ioannis; Kalogeropoulou, Christina; Tsamandas, Athanasios; Chaveles, Ioannis

    2015-01-01

    Insulinomas are the most common pancreatic neuroendocrine tumors. Most insulinomas are benign, small, intrapancreatic solid tumors and only large tumors have a tendency for malignancy. Most patients present with symptoms of hypoglycemia that are relieved with the administration of glucose. We herein present the case of a 75-year-old woman who presented with an acute hypoglycemic episode. Subsequent laboratory and radiological studies established the diagnosis of a 17-cm malignant insulinoma, with local invasion to the left kidney, lymph node metastasis, and hepatic metastases. Patient symptoms, diagnostic and imaging work-up and surgical management of both the primary and the metastatic disease are reviewed. PMID:25960993

  5. Natural History of Malignant Bone Disease in Gastric Cancer: Final Results of a Multicenter Bone Metastasis Survey

    PubMed Central

    Silvestris, Nicola; Pantano, Francesco; Ibrahim, Toni; Gamucci, Teresa; De Vita, Fernando; Di Palma, Teresa; Pedrazzoli, Paolo; Barni, Sandro; Bernardo, Antonio; Febbraro, Antonio; Satolli, Maria Antonietta; Bertocchi, Paola; Catalano, Vincenzo; Giommoni, Elisa; Comandone, Alessandro; Maiello, Evaristo; Riccardi, Ferdinando; Ferrara, Raimondo; Trogu, Antonio; Berardi, Rossana; Leo, Silvana; Bertolini, Alessandro; Angelini, Francesco; Cinieri, Saverio; Russo, Antonio; Pisconti, Salvatore; Brunetti, Anna Elisabetta; Azzariti, Amalia; Santini, Daniele

    2013-01-01

    Background Bone metastasis represents an increasing clinical problem in advanced gastric cancer (GC) as disease-related survival improves. In literature, few data on the natural history of bone disease in GC are available. Patients and Methods Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 208 deceased GC patients with evidence of bone metastasis were statistically analyzed. Results Median time to bone metastasis was 8 months (CI 95%, 6.125–9.875 months) considering all included patients. Median number of SREs/patient was one. Less than half of the patients (31%) experienced at least one and only 4 and 2% experienced at least two and three events, respectively. Median times to first and second SRE were 2 and 4 months, respectively. Median survival was 6 months after bone metastasis diagnosis and 3 months after first SRE. Median survival in patients who did not experience SREs was 5 months. Among patients who received zoledronic acid before the first SRE, the median time to appearance of first SRE was significantly prolonged compared to control (7 months vs 4 months for control; P: 0.0005). Conclusions To our knowledge, this retrospective analysis is the largest multicenter study to demonstrate that bone metastases from GC are not so rare, are commonly aggressive and result in relatively early onset of SREs in the majority of patients. Indeed, our large study, which included 90 patients treated with ZOL, showed, for the first time in literature, a significant extension of time to first SRE and increase in the median survival time after diagnosis of bone metastasis. Taken together, these data may support the beneficial effects of ZOL in GC patients. PMID:24204569

  6. Malignancy and chronic renal failure.

    PubMed

    Peces, Ramon

    2003-01-01

    Increased incidence of cancer at various sites is observed in patients with end-stage renal disease (ESRD). Certain malignant diseases, such as lymphomas and carcinomas of the kidney, prostate, liver and uterus, show an enhanced prevalence compared with the general population. In particular, renal cell carcinoma (RCC) shows an excess incidence in ESRD patients. A multitude of factors, directly or indirectly associated with the renal disease and the treatment regimens, may contribute to the increased tumor formation in these patients. Patients undergoing renal replacement therapy (RRT) are prone to develop acquired cystic kidney disease (ACKD), which may subsequently lead to the development of RCC. In pre-dialysis patients with coexistent renal disease, as in dialysis and transplant patients, the presence of ACKD may predispose to RCC. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse, are additional risk factors for malignancy. Malignancy following renal transplantation is an important medical problem during the follow-up. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. The type of malignancy is different in various countries and dependent on genetic and environmental factors. Finally, previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and post-malignancy screening.

  7. 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.

  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 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.

  10. 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

  11. [Advances in research of dihydroartemisinin against parasitic diseases].

    PubMed

    Li, Hong-Jun; Wang, Wei; Liang, You-Sheng

    2011-08-01

    Dihydroartemisinin, the main metabolite of artemisinin and two artemisinin derivatives, artemether and artesunate, is a broad-spectrum anti-parasitic drug. The present paper systematically reviews the advances in research of dihydroartemisinin against Plasmodium, Schistosoma, Pneumocystis, Toxoplasma, Trichomonas vaginalis, Leishmania, Giardia lamblia.

  12. 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

  13. 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.

  14. A 5-day cytoreductive chemotherapy followed by haplo-identical hsct (FA5-BUCY) as a tumor-ablative regimen improved the survival of patients with advanced hematological malignancies

    PubMed Central

    Chen, Ping; Yuan, Xiaohong; Luo, Xiaofeng; Liu, Tingbo; Zheng, Jing; Zheng, Zhihong; Zheng, Xiaoyun; Chen, Xinji; Zhang, Langhui; Zheng, Hao; Chen, Zaisheng; Hua, Xueling; Le, Shaohua; Li, Jian; Chen, Zhizhe; Hu, Jianda

    2016-01-01

    Haplo-HSCT has been used when HLA-matched siblings are not available. Conditioning regimens aim to reduce tumor burden prior to HSCT and provide sufficient immunoablation. We report the outcome of haplo-HSCT in 63 consecutive patients from 2/2013 to 12/2015 (19 females/44 males) with high-risk or relapsed/refractory hematological malignancies (n=29-AML; 8-sAML; 19-ALL; 5-advanced-MDS; 2-CML-BC). Median age was 20 years (range: 1.1-49). Twenty-one patients achieved remission prior to transplant, while 42 did not. Patients received FA5-BUCY, i.e., 5-day salvage chemotherapy (Fludarabine/Ara-C) and conditioning (Busulfan/Cyclophosphamide). GvHD prophylaxis included ATG, CsA, MMF and short-term MTX. All patients received stem cells from bone marrow and peripheral blood, and achieved successful engraftment, except two who died before. With a median follow-up of 269 days (120-1081), 42/63 patients are still alive and disease-free. Two-year OS and RFS were similar in patients not in remission and in those in complete remission (61.3% vs 56.3%, p=0.88; 58.3% vs 56.3%, p=0.991). Non-relapse mortality and relapse incidence were 22.2% and 11.1%, respectively. Severe acute-GvHD occurred in 4/63 patients. Transplant-related mortality was low at day+100 (17.5%) and for the entire study period (20.6%). Unexpectedly, few patients experienced mild-to-moderate toxicity, and main causes of death were infection and GvHD. BM blast counts, age, and donor-recipient gender-pairs did not affect the outcome. Less chemotherapy cycles prior to HSCT might result in more favorable outcome. Thus, haplo-HSCT with FA5-BUCY appears promising for advanced disease, especially when TBI and amsacrine, used for FLAMSA, are not available and in pediatric patients for whom TBI is not recommended. PMID:27705929

  15. Malignant melanoma of the foot and ankle.

    PubMed

    John, K J; Hayes, D W; Green, D R; Dickerson, J

    2000-04-01

    Malignant melanoma is a serious and devastating skin disease that podiatrists may be called upon to treat. It is pertinent that delays in diagnosis and treatment of malignant melanoma be avoided. Some of the topics discussed in this article are causes, clinical features, classification, and treatment of malignant melanoma, focusing on the foot and ankle.

  16. Malignant Transformation of Pulmonary Benign Metastasizing Leiomyoma

    PubMed Central

    Song, Kyung Sub; Keum, Dong Yoon; Hwang, Il Seon

    2017-01-01

    Pulmonary benign metastasizing leiomyoma (PBML) is defined as metastasis of a leiomyoma to lung tissue. It was first reported in 1937. P BML is known as a benign disease, but can undergo malignant transformation. Only 1 case of the malignant transformation of PBML to leiomyosarcoma has been reported previously. In this report, we present a case of malignant transformation of PBML. PMID:28180107

  17. The role of positron emission tomography with computed tomography in the follow-up of asymptomatic cutaneous malignant melanoma patients with a high risk of disease recurrence.

    PubMed

    Abbott, Rachel Angharad; Acland, Katharine M; Harries, Mark; O'Doherty, Michael

    2011-10-01

    The aim of this study was to evaluate the role of [F] fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) as a surveillance tool in asymptomatic patients with primary cutaneous melanoma with the American Joint Committee on Cancer stage 3 disease. Thirty-four patients with primary cutaneous malignant melanoma with American Joint Committee on Cancer stage 3 disease, who underwent at least one annual surveillance PET/CT scan, were retrospectively identified from our PET Centre Database in May 2008 and their characteristics, PET/CT results and disease course were reviewed. In 20 patients with microscopic stage 3 disease at diagnosis, annual surveillance PET/CT detected two of three recurrences and detected one incidental breast carcinoma. In 14 patients with macroscopic stage 3 disease at, or subsequent to, their initial diagnosis, annual PET/CT detected four of four recurrences, detected metastases in one patient who remains asymptomatic and detected one incidental thyroid carcinoma. PET/CT seems to be a useful surveillance tool in patients with macroscopic stage 3 disease, although the numbers in this study are small. However, the role of PET/CT in patients initially presenting with microscopic stage 3 disease requires further confirmation.

  18. 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

  19. The advance of tomato disease-related microRNAs.

    PubMed

    Wang, Weichen; Luan, Yushi

    2015-07-01

    Tomato is a model plant for studying plant-pathogen interactions. As regulatory factors, microRNAs (miRNAs) have been widely identified and play crucial roles in tomato-pathogen interactions, including host defense and pathogen counter-defense. Here, the review summarizes the discoveries and highlights of miRNAs in tomato diseases. Roles of artificial miRNAs in disease resistance are further discussed. Hence, a better understanding of the contribution of miRNAs in tomato disease will shed light on strategies in enhancing tomato-pathogen resistance.

  20. Periodontitis and Buerger’s Disease: Recent Advances

    PubMed Central

    Pavlic, Verica; Vujic-Aleksic, Vesna; Zubovic, Nina; Gojkov-Vukelic, Mirjana

    2013-01-01

    Buerger’s disease (BD) is a relatively rare thrombotic, occlusive and non-atherosclerotic clinical syndrome of unknown etiology. In recent years, numerous epidemiological studies confirmed the strong association between chronic anaerobic periodontal infection and development of cardiovascular diseases, including BD. Therefore, the aim of this study is to clarify association between periodontal pathogens and Buerger’s disease. Confirmation of presence and identification of periopathogens in patients with BD can be considered crucial in developing novel therapies for BD. Further, periodontal therapy will lead to eventual improvement of BD patients’ condition. PMID:24554799

  1. 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

  2. The Risk of Infection and Malignancy with Tumor Necrosis Factor Antagonists in Adult Patients with Psoriatic Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

    PubMed Central

    Dommasch, E. D.; Abuabara, K.; Shin, D.B.; Nguyen, J.; Troxel, A. B.; Gelfand, J.M.

    2010-01-01

    Background There is a need to better understand the safety of TNF inhibitors in patients with psoriatic disease in whom TNF inhibitors are frequently used as monotherapy. Objective Examine the risks of infection and malignancy with the use of TNF antagonists in adult patients with psoriatic disease. Methods Systematic search for trials of TNF antagonists for adults with plaque psoriasis (PsO) and psoriatic arthritis (PsA). We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, and certolizumab for the treatment of PsO and PsA. 20 out of 820 identified studies with a total of 6,810 patients were included. Results were calculated using fixed effects models and reported as pooled odds ratios (OR). Results ORs for overall infection and serious infection over a mean of 17.8 weeks were 1.18 (95% CI: 1.05, 1.33) and 0.70 (95% CI: 0.40, 1.21), respectively. When adjusting for patient-years, the incidence rate ratio for overall infection was 1.01 (95% CI: 0.92, 1.11). The OR for malignancy was 1.48 (95% CI: 0.71, 3.09), and 1.26 (95% CI: 0.39, 4.15) when non-melanoma skin cancer was excluded. Limitations Short duration of follow-up and rarity of malignancies and serious infections. Conclusions There is a small increased risk of overall infection with the short-term use of TNF antagonists for psoriasis that may be attributable to differences in follow-up time between treatment and placebo groups. There was no evidence of an increased risk of serious infection and a statistically significant increased risk in cancer was not observed with short-term use of TNF inhibitors. PMID:21315483

  3. Advances in the genetically-complex autoinflammatory diseases

    PubMed Central

    Ombrello, Michael J.

    2015-01-01

    Monogenic diseases usually demonstrate Mendelian inheritance and are caused by highly penetrant genetic variants of a single gene. In contrast, genetically-complex diseases arise from a combination of multiple genetic and environmental factors. The concept of autoinflammation originally emerged from the identification of individual, activating lesions of the innate immune system as the molecular basis of the hereditary periodic fever syndromes. In addition to these rare, monogenic forms of autoinflammation, genetically-complex autoinflammatory diseases like the periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, chronic recurrent multifocal osteomyelitis (CRMO), Behçet’s disease, and systemic arthritis also fulfill the definition of autoinflammatory diseases - namely the development of apparently unprovoked episodes of inflammation without identifiable exogenous triggers and in the absence of autoimmunity. Interestingly, investigations of these genetically-complex autoinflammatory diseases have implicated both innate and adaptive immune abnormalities, blurring the line between autoinflammation and autoimmunity. This reinforces the paradigm of concerted innate and adaptive immune dysfunction leading to genetically-complex autoinflammatory phenotypes. PMID:26077134

  4. Advances in the pharmacological management of Huntington's disease.

    PubMed

    Frank, Samuel; Jankovic, Joseph

    2010-03-26

    There is inevitable physical, cognitive and behavioural decline in Huntington's disease (HD), a dominantly inherited progressive neurological disorder. The hallmark of the disease is chorea, an involuntary brief movement that tends to flow between body regions. HD is diagnosed clinically with genetic confirmation. Predictive testing is available; however, it should be undertaken with caution in patients at risk for the disease but without clinical disease expression. Ongoing observational trials have identified not only early subtle motor signs, but also striatal volume, verbal memory and olfaction as possible early manifestations of clinical disease. Multiple areas of the brain degenerate, with dopamine, glutamate and GABA being the predominant neurotransmitters affected in HD. Although many pharmacotherapies have been evaluated targeting these neurotransmitters, few well conducted trials for symptomatic or neuroprotective interventions have yielded positive results. Tetrabenazine is one of the better studied and more effective agents for reducing chorea, although with a risk of potentially serious adverse effects. Newer antipsychotic agents such as olanzapine and aripiprazole may have adequate efficacy with a more favourable adverse-effect profile than older antipsychotics for treating chorea and psychosis. In this review, the pathogenesis, epidemiology and diagnosis of HD are discussed as background for understanding potential pharmacological treatment options. Potential strategies to delay the progression of HD that have been studied and are planned for the future are summarized. Although there is no current method to change the course of this devastating disease, education and symptomatic therapies are effective tools available to clinicians and the families affected by HD.

  5. 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

  6. Nuclear magnetic resonance based metabolomics and liver diseases: Recent advances and future clinical applications

    PubMed Central

    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”. PMID:26755887

  7. 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

    2016-01-07

    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".

  8. 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

  9. Sheep-Associated Malignant Catarrhal Fever-Like Skin Disease in a Free-Ranging Bighorn Sheep ( Ovis canadensis ), Alberta, Canada.

    PubMed

    Slater, Owen M; Peters-Kennedy, Jeanine; Lejeune, Manigandan; Gummer, David; Macbeth, Bryan; Warren, Amy; Joseph, Tomy; Li, Hong; Cunha, Cristina W; Duignan, Pádraig J

    2017-01-01

    Malignant catarrhal fever-like clinical disease was diagnosed in a free-ranging bighorn sheep ( Ovis canadensis ) from Alberta, Canada, in June 2015. Antemortem and gross pathology findings included muscle atrophy, marked weight loss, and bilaterally symmetric alopecia with hyperpigmentation and crusting over the face, medial surfaces of the pinnae, dorsal trunk, distal limbs, perineal area, and tail. Histologically, the skin lesions were characterized by granulomatous mural folliculitis with numerous multinucleated giant cells and fewer lymphocytes and eosinophils consistent with previous reports of chronic ovine herpesvirus-2 (OvHV-2) infection. Multiple skin samples were positive for OvHV-2 DNA on PCR, and on partial sequencing of the viral DNA, there was 94% homology with reference GenBank OvHV-2. Quantitative PCR confirmed an increased level of OvHV-2 DNA in the lesional skin tissues. Based on exclusion of other disease processes, gross and histological lesions, PCR, and viral DNA sequencing results, a diagnosis of OvHV-2-mediated malignant catarrhal fever-like dermatitis was made.

  10. Neuroleptic malignant-like syndrome with a slight elevation of creatine-kinase levels and respiratory failure in a patient with Parkinson’s disease

    PubMed Central

    Wei, Li; Chen, Yinghui

    2014-01-01

    Neuroleptic malignant-like syndrome (NMLS) is a rare but catastrophic complication of drug treatment for Parkinson’s disease (PD). Sudden withdrawal and abrupt reduction of antiparkinsonian drugs are major risk factors. Just as its name suggests, the clinical features of NMLS are similar to neuroleptic malignant syndrome, which is a dangerous adverse response to antipsychotic drugs. Both of these conditions can present with hyperthermia, marked muscle rigidity, altered consciousness, autonomic dysfunction, and elevated serum creatine-kinase (CK) levels. However, we describe a special NMLS case with a slight elevation of CK levels and respiratory failure in the full course of her treatment. The patient, a 68-year-old woman with a 4-years history of Parkinson’s disease, presented with hyperthermia and severe muscular rigidity. During the course of her treatment, her maximum temperature was extremely high (above 41°C). At the beginning, the diagnosis of NMLS secondary to dopamine decrease was difficult to make, because her initial blood examination revealed that her serum CK levels were mildly elevated and decreased to normal range rapidly. Although antiparkinsonian drugs and supportive treatment were applied, the patient developed an acute respiratory failure in the early course of treatment. This case report highlights that when confronted with Parkinson’s patients with high body temperature and muscle rigidity, NMLS should be taken into consideration even if there is no CK elevation. Likewise, the need for supportive care is essential, because its complications are severe, even such as respiratory failure. PMID:24600209

  11. 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

  12. MGMT expression levels predict disease stabilisation, progression-free and overall survival in patients with advanced melanomas treated with DTIC.

    PubMed

    Busch, Christian; Geisler, Jürgen; Lillehaug, Johan R; Lønning, Per Eystein

    2010-07-01

    Metastatic melanoma responds poorly to systemic treatment. We report the results of a prospective single institution study evaluating O(6)-methylguanine-DNA methyltransferase (MGMT) status as a potential predictive and/or prognostic marker among patients treated with dacarbazine (DTIC) 800-1000 mg/m(2) monotherapy administered as a 3-weekly schedule for advanced malignant melanomas. The study was approved by the Regional Ethical Committee. Surgical biopsies from metastatic or loco-regional deposits obtained prior to DTIC treatment were snap-frozen immediately upon removal and stored in liquid nitrogen up to processing. Median time from enrolment to end of follow-up was 67 months. MGMT expression levels evaluated by qRT-PCR correlated significantly to DTIC benefit (CR/PR/SD; p=0.005), time to progression (TTP) (p=0.005) and overall survival (OS) (p=0.003). MGMT expression also correlated to Breslow thickness in the primary tumour (p=0.014). While MGMT promoter hypermethylation correlated to MGMT expression, MGMT promoter hypermethylation did not correlate to treatment benefit, TTP or OS, suggesting that other factors may be critical in determining MGMT expression levels in melanomas. In a Cox proportional regression analysis, serum lactate dehydrogenase (LDH, p<0.001), MGMT expression (p=0.022) and p16(INK4a) expression (p=0.037) independently predicted OS, while TTP correlated to DTIC benefit after 6 weeks only (p=0.001). Our data reveal MGMT expression levels to be associated with disease stabilisation and prognosis in patients receiving DTIC monotherapy for advanced melanoma. The role of MGMT expression as a predictor to DTIC sensitivity versus a general prognostic factor in advanced melanomas warrants further evaluation.

  13. The role of selenium, vitamin C, and zinc in benign thyroid diseases and of selenium in malignant thyroid diseases: Low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma

    PubMed Central

    Moncayo, Roy; Kroiss, Alexander; Oberwinkler, Manfred; Karakolcu, Fatih; Starzinger, Matthias; Kapelari, Klaus; Talasz, Heribert; Moncayo, Helga

    2008-01-01

    Background Thyroid physiology is closely related to oxidative changes. The aim of this controlled study was to evaluate the levels of nutritional anti-oxidants such as vitamin C, zinc (Zn) and selenium (Se), and to investigate any association of them with parameters of thyroid function and pathology including benign and malignant thyroid diseases. Methods This controlled evaluation of Se included a total of 1401 subjects (1186 adults and 215 children) distributed as follows: control group (n = 687), benign thyroid disease (85 children and 465 adults); malignant thyroid disease (2 children and 79 adults). Clinical evaluation of patients with benign thyroid disease included sonography, scintigraphy, as well as the determination of fT3, fT4, TSH, thyroid antibodies levels, Se, Zn, and vitamin C. Besides the routine oncological parameters (TG, TSH, fT4, ultrasound) Se was also determined in the cases of malignant disease. The local control groups for the evaluation of Se levels were taken from a general practice (WOMED) as well as from healthy active athletes. Blood samples were collected between 8:00 and 10:30 a.m. All patients lived in Innsbruck. Statistical analysis was done using SPSS 14.0. The Ho stated that there should be no differences in the levels of antioxidants between controls and thyroid disease patients. Results Among the thyroid disease patients neither vitamin C, nor Zn nor Se correlated with any of the following parameters: age, sex, BMI, body weight, thyroid scintigraphy, ultrasound pattern, thyroid function, or thyroid antibodies. The proportion of patients with benign thyroid diseases having analyte concentrations below external reference cut off levels were 8.7% of cases for vitamin C; 7.8% for Zn, and 20.3% for Se. Low Se levels in the control group were found in 12%. Se levels were significantly decreased in cases of sub-acute and silent thyroiditis (66.4 ± 23.1 μg/l and 59.3 ± 20.1 μg/l, respectively) as well as in follicular and papillary

  14. Disease evaluations and agronomic traits of advanced peanut breeding lines in 2016

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peanut disease evaluations of advanced breeding lines are conducted annually to compare the agronomic traits (crop value, yield, seed grade, and characteristics) and disease resistance of cultivars that are currently available or close to being released for the Southwest. In 2016, a total of 21 com...

  15. 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.

  16. A Phase I and pharmacological study of the glutamine antagonist acivicin with the amino acid solution aminosyn in patients with advanced solid malignancies.

    PubMed

    Hidalgo, M; Rodriguez, G; Kuhn, J G; Brown, T; Weiss, G; MacGovren, J P; Von Hoff, D D; Rowinsky, E K

    1998-11-01

    Acivicin is a glutamine analogue antimetabolite that inhibits several glutamate-dependent synthetic enzymes. Previous studies of this agent administered on a 72-h continuous i.v. infusion schedule every 3 weeks demonstrated a high rate of severe, albeit reversible, central nervous system (CNS) toxicity at the 30 mg/m2/day dose level. Animal studies have shown that the CNS toxicity of acivicin can be prevented by a concomitant infusion of amino acids postulated to block drug uptake in the CNS by a saturable transport system that is common to endogenous amino acids. This study evaluated the feasibility of escalating acivicin doses in cancer patients by administering acivicin with a concomitant 96-h i.v. infusion of a mixture of 16 amino acids (Aminosyn, 10%). Twenty-three patients with advanced malignancies were treated with acivicin on a 72-h continuous infusion schedule at doses ranging from 25 to 60 mg/m2/day every 3 weeks. Reversible, dose-limiting CNS toxicity, characterized by lethargy, confusion, and decreased mental status, occurred in the two patients enrolled at the 60 mg/m2/day dose level, precluding further dose escalation. The maximum tolerated dose (MTD) and recommended dose for additional evaluation of acivicin on this schedule is 50 mg/m2/day. Other toxicities observed were dose-related neutropenia that was grade 4 in four patients (four courses), complicated with fever in three of those patients, and grade 3-4 thrombocytopenia in three patients (three courses). Pharmacokinetics studies performed in 15 patients revealed that the acivicin plasma Css increased from 0.44 microg/ml (range, 0.28-0.59 microg/ml) at the 25 mg/m2/day to 1.06 microg/ml (0.64-1.5 microg/ml) at the 50 mg/m2/dose level. Acivicin Css at the MTD was not significantly higher than previously reported values with single-agent acivicin on the same schedule of administration at the MTD of 25 mg/m2/day dose level (0.60 microg/ml; range, 0.43-0.81 microg/ml). Neurotoxicity did not

  17. Advances in the treatment of visual hallucinations in neurodegenerative diseases

    PubMed Central

    Collerton, Daniel; Taylor, John-Paul

    2013-01-01

    Treatment of visual hallucinations in neurodegenerative disorders is not well advanced. The complexity of underlying mechanisms presents a number of potential avenues for developing treatments, but also suggests that any single one may be of limited efficacy. Reducing medication, with the careful introduction of antidementia medication if needed, is the mainstay of current management. Antipsychotic medication leads to excessive morbidity and mortality and should only be used in cases of high distress that do not otherwise respond. Education, reduction of risk factors and psychological treatments have limited evidence of efficacy, but are unlikely to cause harm. PMID:23882162

  18. 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

  19. Advancing the cellular and molecular therapy for intervertebral disc disease.

    PubMed

    Sakai, Daisuke; Grad, Sibylle

    2015-04-01

    The healthy intervertebral disc (IVD) fulfils the essential function of load absorption, while maintaining multi-axial flexibility of the spine. The interrelated tissues of the IVD, the annulus fibrosus, the nucleus pulposus, and the cartilaginous endplate, are characterised by their specific niche, implying avascularity, hypoxia, acidic environment, low nutrition, and low cellularity. Anabolic and catabolic factors balance a slow physiological turnover of extracellular matrix synthesis and breakdown. Deviations in mechanical load, nutrient supply, cellular activity, matrix composition and metabolism may initiate a cascade ultimately leading to tissue dehydration, fibrosis, nerve and vessel ingrowth, disc height loss and disc herniation. Spinal instability, inflammation and neural sensitisation are sources of back pain, a worldwide leading burden that is challenging to cure. In this review, advances in cell and molecular therapy, including mobilisation and activation of endogenous progenitor cells, progenitor cell homing, and targeted delivery of cells, genes, or bioactive factors are discussed.

  20. Advances in paediatric pulmonary vascular disease associated with bronchopulmonary dysplasia.

    PubMed

    Rossor, Thomas; Greenough, Anne

    2015-02-01

    Pulmonary hypertension (PH) is a common finding in infants with bronchopulmonary dysplasia (BPD). The aim of this review is to describe recent advances in the diagnosis and treatment of PH and discuss whether they will benefit infants and children with BPD related PH. Echocardiography remains the mainstay of diagnosis but has limitations, further developments in diagnostic techniques and identification of biomarkers are required. There are many potential therapies for PH associated with BPD. Inhaled nitric oxide has been shown to improve short term outcomes only. Sidenafil in resource limited settings was shown in three randomized trials to significantly reduce mortality. The efficacy of other therapies including prostacyclin, PDE3 inhibitors and endothelin receptor blockers has only been reported in case reports or case series. Randomized controlled trials with long term follow up are required to appropriately assess the efficacy of therapies aimed at improving the outcome of children with PH.

  1. 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

    2015-10-31

    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.

  2. 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.

  3. [Diabetes in patients with malignant tumors].

    PubMed

    Lengyel, Zoltán; Boér, Katalin; Halászlaki, Csaba; Németh, Zsuzsanna

    2013-09-01

    Disturbances of the carbohydrate metabolism are fairly common is patients with malignancy. On the other hand, diabetes appears to have an effect on the development and progression of various tumors. Malignant diseases and the therapies used in their treatment often have an impact on carbohydrate metabolism, while diabetes may hinder specific oncotherapy or influence oncological therapeutic decisions. Several complications of malignant diseases and some of the medications used in their treatment, such as steroids or parenteral nutrition, may raise blood glucose levels. The various obstacles of oral nutrition frequently seen in patients with malignancy can lead to hypoglycaemia in patients with diabetes. Our article endeavours to review the pathophysiological and clinical connection between diabetes and malignant diseases and the use of insulin, oral antidiabetic drugs and diet in patients with malignant disease.

  4. An assessment of the malignant potential of actinic keratoses and Bowen's disease: p53 and PCNA expression pattern correlate with the number of desmosomes.

    PubMed

    Ramzi, Saeef Taher; Maruno, Motoyoshi; Khaskhely, Noor Mohammad; Khan, Mohammed Abul Kasem; Takamiyagi, Atsushi; Uezato, Hiroshi; Nonaka, Shigeo

    2002-09-01

    Actinic keratoses (AK) and Bowen's disease (BD), both intraepidermal skin tumors, have a potential progression to squamous cell carcinoma (SCC). To evaluate the malignant potential of AK and BD, the expression pattern of p53 protein and proliferating cell nuclear antigen (PCNA) were examined in five types of AK and BD by immunohistochemistry. The ultrastructural difference of epidermal cells between AK and BD lesions was investigated. In the study of p53 and PCNA expression, the atrophic and acantholytic types of AK showed lower positive rates compared to others. These two types did not demonstrate all layers expression pattern. The number of desmosomes of the epidermal cells was significantly reduced in BD, and in the bowenoid and hypertrophic types of AK compared with other types of AK The number of hemi-desmosomes showed greatest reduction in BD and the bowenoid type of AK On the basis of our findings, it is hypothesized that atrophic and acantholytic types of AK may have the lowest, and the bowenoid type of AK and BD may have the highest, malignant potential.

  5. 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

  6. 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

  7. 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

  8. Advances in non-invasive imaging of intracranial vascular disease.

    PubMed Central

    Jäger, H. R.; Grieve, J. P.

    2000-01-01

    Intra-arterial catheter angiography has, in the past, been the mainstay for the investigation of intracranial vascular disease. It is, however, invasive, usually requires in-patients admission, and is associated with a rate of neurological complications between 1% and 3%. In recent years, magnetic resonance angiography (MRA) and CT angiography (CTA) have emerged as non-invasive alternatives for imaging blood vessels and have made a significant impact on neuroradiological investigations. It is the purpose of this article to explain the basic technical principles of these two methods and to give an overview of their current clinical applications. PMID:10700757

  9. 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

  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. 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

  12. von Willebrand disease: advances in pathogenetic understanding, diagnosis, and therapy.

    PubMed

    Lillicrap, David

    2013-01-01

    von Willebrand disease (VWD) is the most common autosomally inherited bleeding disorder. The disease represents a range of quantitative and qualitative pathologies of the adhesive glycoprotein von Willebrand factor (VWF). The pathogenic mechanisms responsible for the type 2 qualitative variants of VWF are now well characterized, with most mutations representing missense substitutions influencing VWF multimer structure and interactions with platelet GPIbα and collagen and with factor VIII. The molecular pathology of type 3 VWD has been similarly well characterized, with an array of different mutation types producing either a null phenotype or the production of VWF that is not secreted. In contrast, the pathogenetic mechanisms responsible for type 1 VWD remain only partially resolved. In the hemostasis laboratory, the measurement of VWF:Ag and VWF:RCo are key components in the diagnostic algorithm for VWD, although the introduction of direct GPIbα-binding assays may become the functional assay of choice. Molecular genetic testing can provide additional benefit, but its utility is currently limited to type 2 and 3 VWD. The treatment of bleeding in VWD involves the use of desmopressin and plasma-derived VWF concentrates and a variety of adjunctive agents. Finally, a new recombinant VWF concentrate has just completed clinical trial evaluation and has demonstrated excellent hemostatic efficacy and safety.

  13. Advances in alcoholic liver disease: An update on alcoholic hepatitis.

    PubMed

    Liang, Randy; Liu, Andy; Perumpail, Ryan B; Wong, Robert J; Ahmed, Aijaz

    2015-11-14

    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.

  14. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT).

    PubMed

    Ullmann, A J; Akova, M; Herbrecht, R; Viscoli, C; Arendrup, M C; Arikan-Akdagli, S; Bassetti, M; Bille, J; Calandra, T; Castagnola, E; Cornely, O A; Donnelly, J P; Garbino, J; Groll, A H; Hope, W W; Jensen, H E; Kullberg, B J; Lass-Flörl, C; Lortholary, O; Meersseman, W; Petrikkos, G; Richardson, M D; Roilides, E; Verweij, P E; Cuenca-Estrella, M

    2012-12-01

    Fungal diseases still play a major role in morbidity and mortality in patients with haematological malignancies, including those undergoing haematopoietic stem cell transplantation. Although Aspergillus and other filamentous fungal diseases remain a major concern, Candida infections are still a major cause of mortality. This part of the ESCMID guidelines focuses on this patient population and reviews pertaining to prophylaxis, empirical/pre-emptive and targeted therapy of Candida diseases. Anti-Candida prophylaxis is only recommended for patients receiving allogeneic stem cell transplantation. The authors recognize that the recommendations would have most likely been different if the purpose would have been prevention of all fungal infections (e.g. aspergillosis). In targeted treatment of candidaemia, recommendations for treatment are available for all echinocandins, that is anidulafungin (AI), caspofungin (AI) and micafungin (AI), although a warning for resistance is expressed. Liposomal amphotericin B received a BI recommendation due to higher number of reported adverse events in the trials. Amphotericin B deoxycholate should not be used (DII); and fluconazole was rated CI because of a change in epidemiology in some areas in Europe. Removal of central venous catheters is recommended during candidaemia but if catheter retention is a clinical necessity, treatment with an echinocandin is an option (CII(t) ). In chronic disseminated candidiasis therapy, recommendations are liposomal amphotericin B for 8 weeks (AIII), fluconazole for >3 months or other azoles (BIII). Granulocyte transfusions are only an option in desperate cases of patients with Candida disease and neutropenia (CIII).

  15. 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.

  16. 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

  17. 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

  18. Malignant tumours after renal transplantation.

    PubMed

    Fahlenkamp, D; Reinke, P; Kirchner, S; Schnorr, D; Lindeke, A; Loening, S A

    1996-10-01

    In 1243 patients after renal transplantation, 39 malignant tumours were detected in 37 patients. The average latency period between transplantation and tumour disease was 72 months. Tumours included 8 malignant lymphomas, 7 dermatomas and 24 visceral tumours. The patients who developed a tumour had received fewer blood transfusions before transplantation than a tumour-free control group of 60 patients with renal transplants. Rejection crises occurred in a significantly smaller number of tumour patients compared with the control group.

  19. Advances in the treatment of diseased equine cheek teeth.

    PubMed

    Tremaine, Henry

    2013-08-01

    The last decade has seen a number of studies that have illuminated our knowledge of hypsodont dental disease and re-examined some of the traditionally performed practices. In addition there has been a major interest in routine preventative dentistry and non-traumatic treatments. These have highlighted some potential risks of the use of modern tools when applied to traditional techniques. This has also led to a reflective review of equine dentistry with the emphasis on attempting to preserve and salvage dental and periodontal tissues, with minimal trauma. In addition, precise imaging and instrumentation have facilitated minimally invasive techniques in conscious sedated horses, and there is renewed interest in comparative dentistry leading to trials with restorative techniques that are practiced in other species.

  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. Recent advances in the molecular analysis of inherited disease.

    PubMed

    Malcolm, S

    1990-12-12

    Many important human genes have been cloned during the last ten years. In some cases, using reverse genetic techniques [Orkin, S. H. (1986) Cell 47, 845-850], disease-causing genes have been isolated whose product was previously unknown. Important examples include the dystrophin protein which, when mutated, gives rise to either Duchenne or Becker muscular dystrophy [Koenig, M., Hoffman, E. P., Bertelson, C. J., Monaco, A. P., Feener, C. and Kunkel, L. M. (1987) Cell 50, 509-517; Monaco, A. P., Bertelson, C. J., Liechti-Gallati, S. & Kunkel, L. M. (1988) Genomics 2, 90-95; Koenig, M., Monaco, A. P. & Kunkel, L. M. (1988) Cell 53, 219-228] and the cystic fibrosis transmembrane conductance regulator (CFTR) [Riordan, J. R., Rommens, J. M., Kerem, B.-S., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J.-L., Drumm, M. L., Ianuzzi, M. C., Collins, F. S. & Tsui, L.-C. (1989) Science 245, 1066-1073]. Recently the technology for systematically detecting single base-pair changes by chemical methods, enzymatic methods or direct DNA sequencing has greatly expanded and simplified. In addition to providing structural information about these clinically important genes and information on disease-causing mutations, these studies have led to an increased understanding of mechanisms of mutation, to the discovery of novel genetic mechanisms and to important clinical applications of carrier detection and pre-natal diagnosis. The recent rapid progress has been made possible by the development of DNA amplification using the polymerase chain reaction (pcr) invented by Saiki and colleagues [Saiki, R. K., Chang, C-A., Levenson, C. H., Warren, T. C., Boehm, C. D., Kazazian, H. H. & Ehrlich, H. A. (1988) N. Engl. J. Med. 319, 537-541].

  2. 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

  3. Cardiovascular complications of radiation therapy for thoracic malignancies: the role for non-invasive imaging for detection of cardiovascular disease

    PubMed Central

    Groarke, John D.; Nguyen, Paul L.; Nohria, Anju; Ferrari, Roberto; Cheng, Susan; Moslehi, Javid

    2014-01-01

    Radiation exposure to the thorax is associated with substantial risk for the subsequent development of cardiovascular disease. Thus, the increasing role of radiation therapy in the contemporary treatment of cancer, combined with improving survival rates of patients undergoing this therapy, contributes to a growing population at risk of cardiovascular morbidity and mortality. Associated cardiovascular injuries include pericardial disease, coronary artery disease, valvular disease, conduction disease, cardiomyopathy, and medium and large vessel vasculopathy—any of which can occur at varying intervals following irradiation. Higher radiation doses, younger age at the time of irradiation, longer intervals from the time of radiation, and coexisting cardiovascular risk factors all predispose to these injuries. The true incidence of radiation-related cardiovascular disease remains uncertain due to lack of large multicentre studies with a sufficient duration of cardiovascular follow-up. There are currently no consensus guidelines available to inform the optimal approach to cardiovascular surveillance of recipients of thoracic radiation. Therefore, we review the cardiovascular consequences of radiation therapy and focus on the potential role of non-invasive cardiovascular imaging in the assessment and management of radiation-related cardiovascular disease. In doing so, we highlight characteristics that can be used to identify individuals at risk for developing post-radiation cardiovascular disease and propose an imaging-based algorithm for their clinical surveillance. PMID:23666251

  4. Moments of homecoming among people with advanced dementia disease in a residential care facility.

    PubMed

    Norberg, Astrid; Ternestedt, Britt-Marie; Lundman, Berit

    2015-10-26

    This study concerns moments of homecoming among people with advanced dementia disease living in a residential care facility. Our main finding from participant observations with nine residents was that the residents showed moments of homecoming, i.e. they alternated between verbal and/or nonverbal expressions of feeling at home and of not feeling at home. If care providers understand that they can help people with advanced dementia disease experience moments of homecoming, they can focus on aspects of care that can promote these experiences.

  5. 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

  6. 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.

  7. 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.

  8. Recent advances in understanding and managing Crohn’s disease

    PubMed Central

    Stange, Eduard F.; Wehkamp, Jan

    2016-01-01

    There is consensus that inflammatory bowel diseases (IBDs) are the result of “dysregulated” immune reactivity towards commensal microorganisms in the intestine. This gut microbiome is clearly altered in IBD, but its primary or secondary role is still debated. The focus has shifted from adaptive to innate immunity, with its multitude of receptor molecules (Toll-like and NOD receptors) and antibacterial effector molecules (defensins, cathelicidin, and others). The latter appear to be at least partly deficient at different intestinal locations. Host genetics also support the notion that microbe–host interaction at the mucosa is the prime site of pathogenesis. In contrast, even the latest therapeutic antibodies are directed against secondary targets like cytokines and integrins identified decades ago. These so-called “biologicals” have disappointing long-term results, with the majority of patients not achieving remission in the long run. A promising approach is the development of novel drugs like defensin-derived molecules that substitute for the missing endogenous antibacterials. PMID:28163902

  9. 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

  10. Phase I dose-escalation study of the mTOR inhibitor sirolimus and the HDAC inhibitor vorinostat in patients with advanced malignancy

    PubMed Central

    Park, Haeseong; Garrido-Laguna, Ignacio; Naing, Aung; Fu, Siqing; Falchook, Gerald S.; Piha-Paul, Sarina A.; Wheler, Jennifer J.; Hong, David S.; Tsimberidou, Apostolia M.; Subbiah, Vivek; Zinner, Ralph G.; Kaseb, Ahmed O.; Patel, Shreyaskumar; Fanale, Michelle A.; Velez-Bravo, Vivianne M.; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

    2016-01-01

    Preclinical models suggest that histone deacetylase (HDAC) and mammalian target of rapamycin (mTOR) inhibitors have synergistic anticancer activity. We designed a phase I study to determine the safety, maximum tolerated dose (MTD), recommended phase II dose (RP2D), and dose-limiting toxicities (DLTs) of combined mTOR inhibitor sirolimus (1 mg-5 mg PO daily) and HDAC inhibitor vorinostat (100 mg-400 mg PO daily) in patients with advanced cancer. Seventy patients were enrolled and 46 (66%) were evaluable for DLT assessment since they completed cycle 1 without dose modification unless they had DLT. DLTs comprised grade 4 thrombocytopenia (n = 6) and grade 3 mucositis (n = 1). Sirolimus 4 mg and vorinostat 300 mg was declared RP2D because MTD with sirolimus 5 mg caused significant thrombocytopenia. The grade 3 and 4 drug-related toxic effects (including DLTs) were thrombocytopenia (31%), neutropenia (8%), anemia (7%), fatigue (3%), mucositis (1%), diarrhea (1%), and hyperglycemia (1%). Of the 70 patients, 35 (50%) required dose interruption or modification and 61 were evaluable for response. Partial responses were observed in refractory Hodgkin lymphoma (−78%) and perivascular epithelioid tumor (−54%), and stable disease in hepatocellular carcinoma and fibromyxoid sarcoma. In conclusion, the combination of sirolimus and vorinostat was feasible, with thrombocytopenia as the main DLT. Preliminary anticancer activity was observed in patients with refractory Hodgkin lymphoma, perivascular epithelioid tumor, and hepatocellular carcinoma. PMID:27589687

  11. [Chronic diseases and complexity: new roles in nursing. Advanced practice nurses and chronic patient].

    PubMed

    Sánchez-Martín, C Inmaculada

    2014-01-01

    The increase in chronic diseases and the progressive ageing of the population is a source of concern for the different agencies with responsibility for health care. This has led to the creation of many documents focused on the analysis of the current situation and care of chronic diseases, including the WHO recommendations intended to assist countries and health services design and implement strategies that will address the existing demand, control and prevention of chronic diseases. In addition, there is a need to respond to the demand generated by chronic diseases in every sense, and from the different systems it is becoming more difficult to get enough support from multidisciplinary teams where the nurse has a central importance. While chronic diseases are becoming a threat due to the costs they generate, it is also an opportunity for nursing to be at the forefront for advanced care requirements, performed by professionals with recognized advanced clinical skills and ability for case management while monitoring and controlling complex chronic patients. The different services of the National Health System have introduced nurses that play different roles (cases managers, liaison nurses, advanced practice nurses and so on). However, it could be argued that they are not being trained to a desirable development level. It is therefore time for health care authorities to determine the role of the advanced practice nurse in relation to functional positions, and allow them to make an advance in the development of unified skills for the whole National Health System. From our experience we have learned that the advanced practice nurse is a resource that helps in the sustainability of services, thanks to the efficiency shown in the results obtained from the care given to both chronic and complex chronic patients.

  12. Advances in MR imaging assessment of adults with congenital heart disease.

    PubMed

    Kathiria, Nazima N; Higgins, Charles B; Ordovas, Karen G

    2015-02-01

    Many novel cardiac MR sequences can be used for assessment of adult patients with congenital heart disease. Although most of these techniques are still primarily used in the research arena, there are many potential applications in clinical practice. Advanced cardiac MR assessment of myocardial tissue characterization, flow hemodynamics, and myocardial strain are promising tools for diagnostic and prognostic assessment late after repair of congenital heart diseases.

  13. Advances in sickle cell disease treatment: from drug discovery until the patient monitoring.

    PubMed

    dos Santos, Jean Leandro; Lanaro, Carolina; Chin, Chung Man

    2011-04-01

    Sickle cell disease (SCD) is one of the most prevalent hematological diseases in the world. Despite the immense progress in molecular knowledge about SCD in last years few therapeutical sources are currently available. Nowadays the treatment is performed mainly with drugs such as hydroxyurea or other fetal hemoglobin inducers and chelating agents. This review summarizes current knowledge about the treatment and the advancements in drug design in order to discover more effective and safe drugs. Patient monitoring methods in SCD are also discussed.

  14. 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

  15. Primary malignant melanoma, of head and neck: a comprehensive review of literature.

    PubMed

    Vikey, A K; Vikey, Deepali

    2012-05-01

    Malignant melanoma; since long time is considered as deadly disease, but risk factor is minimized due to new technologies, substantial literatures, and promising treatments. The diverse etiopathogenesis; including physical carcinogens, bio-molecules, biological behavior, anatomical locations, and negligence; contribute to complexity of disease. So even after advanced medical technology, malignant melanoma is the challenge to doctors as well as common public. There is increase in incidence rate day by day, which directly attributes to recent concept of sun beds or tanning beds and global climate. After considering its severity, different researches are carried out in the field of radiology and biotechnology. But again these are not sufficient to control the disease. However; to reduce the mortality there is need of general public awareness regarding causative factors and preventive measures. Many literatures recently advocate for long time survival of malignant melanoma, after its early detection and treatment.

  16. 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

  17. 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.

  18. Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology.

    PubMed

    Cornely, Oliver A; Böhme, Angelika; Buchheidt, Dieter; Einsele, Hermann; Heinz, Werner J; Karthaus, Meinolf; Krause, Stefan W; Krüger, William; Maschmeyer, Georg; Penack, Olaf; Ritter, Jörg; Ruhnke, Markus; Sandherr, Michael; Sieniawski, Michal; Vehreschild, Jörg-Janne; Wolf, Hans-Heinrich; Ullmann, Andrew J

    2009-01-01

    There is no widely accepted standard for antifungal prophylaxis in patients with hematologic malignancies. The Infectious Diseases Working Party of the German Society for Haematology and Oncology assigned a committee of hematologists and infectious disease specialists to develop recommendations. Literature data bases were systematically searched for clinical trials on antifungal prophylaxis. The studies identified were shared within the committee. Data were extracted by two of the authors (OAC and MSi). The consensus process was conducted by email communication. Finally, a review committee discussed the proposed recommendations. After consensus was established the recommendations were finalized. A total of 86 trials were identified including 16,922 patients. Only a few trials yielded significant differences in efficacy. Fluconazole 400 mg/d improved the incidence rates of invasive fungal infections and attributable mortality in allogeneic stem cell recipients. Posaconazole 600 mg/d reduced the incidence of IFI and attributable mortality in allogeneic stem cell recipients with severe graft versus host disease, and in patients with acute myelogenous leukemia or myelodysplastic syndrome additionally reduced overall mortality. Aerosolized liposomal amphotericin B reduced the incidence rate of invasive pulmonary aspergillosis. Posaconazole 600 mg/d is recommended in patients with acute myelogenous leukemia/myelodysplastic syndrome or undergoing allogeneic stem cell recipients with graft versus host disease for the prevention of invasive fungal infections and attributable mortality (Level A I). Fluconazole 400 mg/d is recommended in allogeneic stem cell recipients until development of graft versus host disease only (Level A I). Aerosolized liposomal amphotericin B is recommended during prolonged neutropenia (Level B II).

  19. Gynaecological Malignancies from Palliative Care Perspective

    PubMed Central

    Mishra, Kamlesh

    2011-01-01

    Of the approximately 80,000 new cases of all cancers detected every year in India, 10–15% are gynecological malignancies. As per population-based registries under the National Cancer Registry Program, the leading sites of cancer among women are the cervix uteri, breast, and oral cavity. About 50–60% of all cancers among women in India are mainly of the following four organs: cervix uteri, breast, corpus uteri, and ovaries. Over 70% of these women report for diagnostic and treatment services at an advanced stage of disease, resulting in poor survival and high mortality rates. Among all gynecological cancers, ovarian cancer is the deadliest one and, in 2/3rd of the cases, is detected in an advanced stage. But, in India and in other developing countries, due to inadequate screening facilities for the preventable cancer cervix, this kills more women than any other cancer in females. Gynecology Oncologist as a sub-specialist has an immensely important role in curtailing the menace of gynecological malignancies by providing comprehensive preventive, curative, palliative and follow-up services, with the aim of assuring a good quality of life to women as a cornerstone of cancer management. PMID:21811372

  20. 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

  1. 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.

  2. 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...

  3. Disease evaluations and agronomic traits of advanced peanut breeding lines in 2013

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A total of 21 peanut cultivars and high-oleic advanced breeding lines were evaluated in small field plots in 2013 for agronomic traits (crop value, yield, seed grade, and characteristics) and resistance to diseases (Sclerotinia blight, southern blight, and Pythium and Rhizoctonia pod rot). Among th...

  4. 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…

  5. 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.

  6. Safety and Efficacy of BL-8040 for the Mobilization of Donor Hematopoietic Stem Cells and Allogeneic Transplantation in Patients With Advanced Hematological Malignancies

    ClinicalTrials.gov

    2017-02-02

    Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Non-Hodgkin's Lymphoma; Non-Hodgkin Lymphoma; Hodgkin Disease; Hodgkins Disease; Hodgkin's Disease; Multiple Myeloma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm

  7. An incidental finding of a nodal recurrence of cutaneous malignant melanoma after a 45-year disease-free period.

    PubMed

    Goodenough, Jenny; Cozon, Caroline Louise; Liew, Se Hwang

    2014-06-03

    We report the case of an 84-year-old woman who had a nodal recurrence of melanoma 45 years after the primary diagnosis of an extremity cutaneous melanoma. It is believed to be the longest disease-free latency period reported between primary melanoma diagnosis and recurrence to date. Late recurrences of melanoma are rare and recurrence after four decades extremely rare. This article suggests melanoma is a disease with a potentially lifelong risk of recurrence and thus clinicians and patients must be vigilant and aware of this risk, particularly if late recurrences are to be recognised early and management optimised.

  8. Idiopathic Inflammatory Myopathies and Malignancy: a Comprehensive Review.

    PubMed

    Tiniakou, Eleni; Mammen, Andrew L

    2017-02-01

    The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases (collectively known as myositis) affecting the skeletal muscles as well as other organ systems such as skin, lungs, and joints. The primary forms of myositis include polymyositis (PM), dermatomyositis (PM), and immune-mediated necrotizing myopathy (IMNM). Patients with these diseases experience progressive proximal muscle weakness, have characteristic muscle biopsy findings, and produce autoantibodies that are associated with unique clinical features. One distinguishing feature of these patients is that they are also known to have an increased risk of cancer. Since the first description of the association in 1916, it has been extensively reported in the medical literature. However, there have been significant variations between the different studies with regard to the degree of cancer risk in patients with IIM. These discrepancies can, in part, be attributed to differences in the definition of malignancy-associated myositis used in different studies. In recent years, significant advances have been made in defining specific features of IIM that are associated with the development of malignancy. One of these has been myositis-specific antibodies (MSAs), which are linked to distinct clinical phenotypes and categorize patients into groups with more homogeneous features. Indeed, patients with certain MSAs seem to be at particularly increased risk of malignancy. This review attempts a systematic evaluation of research regarding the association between malignancy and myositis.

  9. Biologic response modifiers in gynecologic malignancies.

    PubMed Central

    Dutcher, J. P.; Wadler, S.; Wiernik, P. H.

    1988-01-01

    Biological therapy is currently being investigated in the treatment of a number of malignancies. The hypothesis for the use of this therapeutic modality involves an attempt to stimulate an already existent but perhaps suboptimal immune response to foreign protein, including tumor. Immunologic therapy appears to work best against small-volume disease, as indicated from animal studies. This condition is potentially achievable in advanced ovarian cancer, where surgery is capable of producing multi-log reduction in tumor mass, and thus immunotherapy may be an option in this disease. The attraction of biologic therapy in patients with ovarian cancer is the potential to treat relatively localized but often chemotherapy-resistant disease. In cervical cancer, the rationale for the use of interferon is somewhat different in that this disease may be a manifestation of a virally induced proliferative lesion. Thus, the antiviral properties of interferon are being investigated in both limited and advanced cervical cancer. Both of these hypothesis have pre-clinical data to support them. This paper presents the pre-clinical and clinical work currently available for consideration of future use. PMID:2461003

  10. 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

  11. 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.

  12. Selective inhibitors of phosphoinositide 3-kinase delta: modulators of B-cell function with potential for treating autoimmune inflammatory diseases and B-cell malignancies

    PubMed Central

    Puri, Kamal D.; Gold, Michael R.

    2012-01-01

    The delta isoform of the p110 catalytic subunit (p110δ) of phosphoinositide 3-kinase is expressed primarily in hematopoietic cells and plays an essential role in B-cell development and function. Studies employing mice lacking a functional p110δ protein, as well as the use of highly-selective chemical inhibitors of p110δ, have revealed that signaling via p110δ-containing PI3K complexes (PI3Kδ) is critical for B-cell survival, migration, and activation, functioning downstream of key receptors on B cells including the B-cell antigen receptor, chemokine receptors, pro-survival receptors such as BAFF-R and the IL-4 receptor, and co-stimulatory receptors such as CD40 and Toll-like receptors (TLRs). Similarly, this PI3K isoform plays a key role in the survival, proliferation, and dissemination of B-cell lymphomas. Herein we summarize studies showing that these processes can be inhibited in vitro and in vivo by small molecule inhibitors of p110δ enzymatic activity, and that these p110δ inhibitors have shown efficacy in clinical trials for the treatment of several types of B-cell malignancies including chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). PI3Kδ also plays a critical role in the activation, proliferation, and tissue homing of self-reactive B cells that contribute to autoimmune diseases, in particular innate-like B-cell populations such as marginal zone (MZ) B cells and B-1 cells that have been strongly linked to autoimmunity. We discuss the potential utility of p110δ inhibitors, either alone or in combination with B-cell depletion, for treating autoimmune diseases such as lupus, rheumatoid arthritis, and type 1 diabetes. Because PI3Kδ plays a major role in both B-cell-mediated autoimmune inflammation and B-cell malignancies, PI3Kδ inhibitors may represent a promising therapeutic approach for treating these diseases. PMID:22936933

  13. 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.

  14. Advances in understanding and treating liver diseases during pregnancy: A review.

    PubMed

    Kamimura, Kenya; Abe, Hiroyuki; Kawai, Hirokazu; Kamimura, Hiroteru; Kobayashi, Yuji; Nomoto, Minoru; Aoyagi, Yutaka; Terai, Shuji

    2015-05-07

    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.

  15. Malignant hyperthermia

    MedlinePlus

    ... a fast rise in body temperature and severe muscle contractions when someone with the disease gets general anesthesia . It is passed down through families. Hyperthermia means high body ... from medical emergencies such as heat stroke or infection.

  16. Malignant Catatonia Mimicking Pheochromocytoma

    PubMed Central

    Li, Dailin

    2013-01-01

    Malignant catatonia is an unusual and highly fatal neuropsychiatric condition which can present with clinical and biochemical manifestations similar to those of pheochromocytoma. Differentiating between the two diseases is essential as management options greatly diverge. We describe a case of malignant catatonia in a 20-year-old male who presented with concurrent psychotic symptoms and autonomic instability, with markedly increased 24-hour urinary levels of norepinephrine at 1752 nmol/day (normal, 89–470 nmol/day), epinephrine at 1045 nmol/day (normal, <160 nmol/day), and dopamine at 7.9 μmol/day (normal, 0.4–3.3 μmol/day). The patient was treated with multiple sessions of electroconvulsive therapy, which led to complete clinical resolution. Repeat urine collections within weeks of this presenting event revealed normalization or near normalization of his catecholamine and metanephrine levels. Malignant catatonia should be considered in the differential diagnosis of the hypercatecholamine state, particularly in a patient who also exhibits concurrent catatonic features. PMID:24251048

  17. Divergent Activity Profiles of Type 1 Ryanodine Receptor Channels Carrying Malignant Hyperthermia and Central Core Disease Mutations in the Amino-Terminal Region.

    PubMed

    Murayama, Takashi; Kurebayashi, Nagomi; Yamazawa, Toshiko; Oyamada, Hideto; Suzuki, Junji; Kanemaru, Kazunori; Oguchi, Katsuji; Iino, Masamitsu; Sakurai, Takashi

    2015-01-01

    The type 1 ryanodine receptor (RyR1) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal muscle and is mutated in several diseases, including malignant hyperthermia (MH) and central core disease (CCD). Most MH and CCD mutations cause accelerated Ca2+ release, resulting in abnormal Ca2+ homeostasis in skeletal muscle. However, how specific mutations affect the channel to produce different phenotypes is not well understood. In this study, we have investigated 11 mutations at 7 different positions in the amino (N)-terminal region of RyR1 (9 MH and 2 MH/CCD mutations) using a heterologous expression system in HEK293 cells. In live-cell Ca2+ imaging at room temperature (~25 °C), cells expressing mutant channels exhibited alterations in Ca2+ homeostasis, i.e., an enhanced sensitivity to caffeine, a depletion of Ca2+ in the ER and an increase in resting cytoplasmic Ca2+. RyR1 channel activity was quantitatively evaluated by [3H]ryanodine binding and three parameters (sensitivity to activating Ca2+, sensitivity to inactivating Ca2+ and attainable maximum activity, i.e., gain) were obtained by fitting analysis. The mutations increased the gain and the sensitivity to activating Ca2+ in a site-specific manner. The gain was consistently higher in both MH and MH/CCD mutations. Sensitivity to activating Ca2+ was markedly enhanced in MH/CCD mutations. The channel activity estimated from the three parameters provides a reasonable explanation to the pathological phenotype assessed by Ca2+ homeostasis. These properties were also observed at higher temperatures (~37 °C). Our data suggest that divergent activity profiles may cause varied disease phenotypes by specific mutations. This approach should be useful for diagnosis and treatment of diseases with mutations in RyR1.

  18. Gene Expression Profiles in Peripheral Blood Mononuclear Cells Can Distinguish Patients with Non-Small-Cell Lung Cancer from Patients with Non-Malignant Lung Disease

    PubMed Central

    Showe, Michael K.; Vachani, Anil; Kossenkov, Andrew V.; Yousef, Malik; Nichols, Calen; Nikonova, Elena V.; Chang, Celia; Kucharczuk, John; Tran, Bao; Wakeam, Elliot; Yie, Ting An; Speicher, David; Rom, William N.; Albelda, Steven

    2009-01-01

    Early diagnosis of lung cancer followed by surgery presently is the most effective treatment for non-small-cell lung cancer (NSCLC). An accurate, minimally invasive test that could detect early disease would permit timely intervention and potentially reduce mortality. Recent studies have shown that the peripheral blood can carry information related to the presence of disease, including prognostic information and information on therapeutic response. We have analyzed gene expression in peripheral blood mononuclear cell (PBMC) samples including 137 patients with NSCLC tumors and 91 patient controls with non-malignant lung conditions, including histologically diagnosed benign nodules. Subjects were primarily smokers and former smokers. We have identified a 29-gene signature that separates these two patient classes with 86% accuracy (91% sensitivity, 80% specificity). Accuracy in an independent validation set, including samples from a new location, was 78% (sensitivity of 76% and specificity of 82%). An analysis of this NSCLC-gene signature in 18 NSCLCs taken pre-surgery, with matched samples from 2-5 months post-surgery, showed that in 78% of cases, the signature was reduced post-surgery and disappeared entirely in 33%. Our results demonstrate the feasibility of using peripheral blood gene expression signatures to identify early-stage NSCLC in at-risk populations. PMID:19951989

  19. 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

  20. Molecular forms of prostate-specific antigen in the serum of women with benign and malignant breast diseases.

    PubMed Central

    Borchert, G. H.; Melegos, D. N.; Tomlinson, G.; Giai, M.; Roagna, R.; Ponzone, R.; Sgro, L.; Diamandis, E. P.

    1997-01-01

    Using a highly sensitive immunofluorometric procedure, we measured the total prostate-specific antigen (PSA) concentration in 632 sera obtained from female blood donors and women with idiopathic hirsutism, breast cancer or benign breast diseases. A total of 50 sera with total PSA > 15 ng l(-1) were fractionated by high-performance liquid chromatography (HPLC) in order to resolve the two immunoreactive molecular forms, i.e. free PSA (approximately 30 kDa) and PSA bound to alpha1-antichymotrypsin (PSA-ACT, 100 kDa). We found that breast cancer patients have presurgical serum total PSA levels similar to those of blood donors. Total serum PSA concentration decreases with age in women with idiopathic hirsutism, in cancer patients and in patients with benign breast diseases. The major molecular form of PSA in the serum of all normal and hirsute women (n = 15) is PSA bound to the proteinase inhibitor alpha1-antichymotrypsin. The major molecular form in 44% of presurgical cancer patient sera is free PSA. A total of 58% of benign breast disease patients also have in their serum mainly free PSA. We conclude that about half the patients with breast cancer or benign breast diseases have free PSA as the major molecular form in their serum, whereas patients without breast pathologies (normal blood donors, idiopathic hirsutism) have PSA bound to alpha1-antichymotrypsin as the major molecular form. The ratio of PSA/PSA-ACT may have value as a simple biochemical test for diagnosis of breast pathologies including breast cancer. PMID:9376271

  1. 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.

  2. 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.

  3. Epidemiological Survey of Sinonasal Malignancy in North-East Iran

    PubMed Central

    Poursadegh, Mehdi; Poursadegh, Farid; Esmaeili, Majid; Bakhshaee, Mehdi

    2015-01-01

    Introduction: Sinonasal malignancies are uncommon neoplasms with several histological subtypes. These malignancies have a poor prognosis and, because of the nonspecific nature of the symptoms, most patients are diagnosed late when the disease is already at an advanced stage. Therefore, most sinonasal malignancies tend to be treated with surgery and postoperative radiotherapy. Understanding the incidence and prevalence of clinical symptoms, pathology, diagnosis, and subsequent prognosis of the disease is important for early diagnosis. Materials and Methods: Medical records of patients with a confirmed diagnosis of sinonasal malignancy in a tertiary referral center from 1998 to 2009 were retrospectively investigated by chronological examination. Information relating to symptoms, pathology, and treatment of patients were collected from the checklists and used to generate tables and graphs, while descriptive statistical tests were used to compare data. Results: The records of 69 patients were examined, including 45 (65.2%) male and 24 (34.8%) female patients with a combined mean age of 54.07±16.04 years. Twenty-one patients (30.4%) were aged less than 45 years and 48 (69.6%) were more than 45 years of age. The most common symptom was facial swelling in 46 (66.6%) patients and the most common kind of tumor was squamous cell carcinoma in 28 (40.6%) patients. The primary location of the tumor in most patients was the maxillary sinus (54 patients; 78.3%). A majority of patients present in advanced stage (stage III or more) with intraorbital (39.1%) or intracranial (4.3%) involvement, or regional lymphatic (28.99%) or distance metastasis (7.2%). The most common treatment was surgery (17 patients; 24.6%). Conclusion: Due to their nonspecific symptoms, most sinonasal malignancies are diagnosed at an advanced stage of the disease. Therefore, all patients with nonspecific symptoms, especially older males, should be evaluated for sinonasal malignancies in order to

  4. Malignant lymphoma of bone.

    PubMed

    Dürr, Hans Roland; Müller, Peter Ernst; Hiller, Erhard; Maier, Markus; Baur, Andrea; Jansson, Volkmar; Refior, Hans Jürgen

    2002-02-01

    Malignant lymphoma of bone is rare. In many cases, its diagnosis is delayed because of unspecific clinical signs and equivocal radiographs. Therapy in general is multimodal, including surgery and radio- and chemotherapy. Our objective was to demonstrate the clinical and radiological aspects of the lesion to optimize diagnostic approaches and to evaluate treatment and prognostic factors. Thirty-six patients with malignant lymphoma of bone who were surgically treated over a 15-year-period were retrospectively reviewed. Seventeen of them showed a singular bone non-Hodgkin's lymphoma (NHL) which was classified as primary lymphoma of the bone (PLB). In 13 cases, dissemination of the disease with multiple bone or visceral involvement was apparent (dNHL). Six patients suffered from bone involvement due to Hodgkin's disease (HD). Surgical treatment was indicated for diagnostic reasons or complications due to the disease. Radiation and chemotherapy were part of the oncological treatment. The patients' mean age was 57 years. The main symptom in malignant bone lymphoma in 33 patients was pain, with an average duration of 8 months. In the secondary cases, bone involvement appeared on average 57 months after the initial diagnosis. An osteolytic pattern was seen in 58% of the lesions. Soft-tissue involvement was seen in 71% of cases (PLB 80%, dNHL 73%, HD 40%) and was the primary diagnostic sign associated with this disease. The 5-year survival rate was 61% (PLB 88%, dNHL 38%, HD 50%). Multiple vs solitary bone involvement was the most significant factor in the prognosis. Extraskeletal involvement significantly decreased survival. No correlation was found between gender, age, location, or histological subtypes and survival. Bone involvement in NHL appears late in the extraskeletal disease. The clinical appearance is nonspecific, and the delay between the onset of symptoms and diagnosis is often long. One of the major radiologic signs is the existence of a soft-tissue tumor

  5. Proteomics and plant disease: advances in combating a major threat to the global food supply.

    PubMed

    Rampitsch, Christof; Bykova, Natalia V

    2012-02-01

    The study of plant disease and immunity is benefiting tremendously from proteomics. Parallel streams of research from model systems, from pathogens in vitro and from the relevant pathogen-crop interactions themselves have begun to reveal a model of how plants succumb to invading pathogens and how they defend themselves without the benefit of a circulating immune system. In this review, we discuss the contribution of proteomics to these advances, drawing mainly on examples from crop-fungus interactions, from Arabidopsis-bacteria interactions, from elicitor-based model systems and from pathogen studies, to highlight also the important contribution of non-crop systems to advancing crop protection.

  6. 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.

  7. Recent Advances in Kawasaki Disease - Proceedings of the 3rd Kawasaki Disease Summit, Chandigarh, 2014.

    PubMed

    Singh, Surjit; Sharma, Dhrubajyoti; Bhattad, Sagar; Phillip, Saji

    2016-01-01

    Kawasaki disease (KD) is the most common cause of acquired heart disease in children in Japan, North America and Europe. It is now being increasingly recognized from the developing countries as well. If not diagnosed and treated in time, KD can result in coronary artery abnormalities in approximately 15-25% cases. The long-term consequences of these abnormalities may manifest in adults as myocardial ischemia and congestive heart failure. Intravenous immunoglobulin (IVIg) remains the drug of choice for treatment of KD, but several new agents like infliximab, cyclosporine, glucocorticoids and statins are now being increasingly used in these patients. While echocardiography has been the preferred imaging modality hitherto, CT coronary angiography has emerged as an exciting new supplementary option and provides an entirely new dimension to this disease. The incidence of KD has shown a progressive increase in several countries and it is likely that this disease would impact public health programmes in the near future even in the developing countries.

  8. Eosinophilic Dermatosis of Hematologic Malignancy.

    PubMed

    Lucas-Truyols, S; Rodrigo-Nicolás, B; Lloret-Ruiz, C; Quecedo-Estébanez, E

    2017-03-22

    Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most commonly associated malignancy is chronic lymphocytic leukemia. Eosinophilic dermatosis of hematologic malignancy is a rare condition with a wide variety of clinical presentations, ranging from papules, erythematous nodules, or blisters that simulate arthropod bites, to the formation of true plaques of differing sizes. Histology reveals the presence of abundant eosinophils. We present 4 new cases seen in Hospital Arnau de Vilanova, Valencia, during the past 7 years. Three of these cases were associated with chronic lymphocytic leukemia and 1 with mycosis fungoides. It is important to recognize this dermatosis as it can indicate progression of the underlying disease, as was the case in 3 of our patients.

  9. Recent advances in host defense mechanisms/therapies against oral infectious diseases and consequences for systemic disease.

    PubMed

    Gaffen, S L; Herzberg, M C; Taubman, M A; Van Dyke, T E

    2014-05-01

    The innate and adaptive immune systems are both crucial to oral disease mechanisms and their impact on systemic health status. Greater understanding of these interrelationships will yield opportunities to identify new therapeutic targets to modulate disease processes and/or increase host resistance to infectious or inflammatory insult. The topics addressed reflect the latest advances in our knowledge of the role of innate and adaptive immune systems and inflammatory mechanisms in infectious diseases affecting the oral cavity, including periodontitis and candidiasis. In addition, several potential links with systemic inflammatory conditions, such as cardiovascular disease, are explored. The findings elucidate some of the defense mechanisms utilized by host tissues, including the role of IL-17 in providing immunity to oral candidiasis, the antimicrobial defense of mucosal epithelial cells, and the pro-resolution effects of the natural inflammatory regulators, proresolvins and lipoxins. They also describe the role of immune cells in mediating pathologic bone resorption in periodontal disease. These insights highlight the potential for therapeutic benefit of immunomodulatory interventions that bolster or modulate host defense mechanisms in both oral and systemic disease. Among the promising new therapeutic approaches discussed here are epithelial cell gene therapy, passive immunization against immune cell targets, and the use of proresolvin agents.

  10. [Metachronous four primary malignancies in gastro-intestinal tract].

    PubMed

    Bae, Jung Min; Kim, Se Won; Kim, Sang Woon; Song, Sun Kyo

    2009-06-01

    Multiple primary malignancy was reported firstly by Billroth in 1889. Recently, multiple primary malignancies are considered to increase due to improved survival rate of cancer patients, advanced diagnostic tools, and increased use of chemotherapy and radiotherapy. In Korea, several cases of triple primary malignancies were reported. However, four primary malignancies in gastro-intestinal tract was rarely reported. Recently, we experienced a 70 year-old male who was diagnosed with metachronous four primary malignancies in rectum, ascending colon, stomach, and ampulla of Vater. We report this rare case of metachronous four primary malignancies with a review of literature.

  11. Genetics and molecular pathology of gastric malignancy: Development of targeted therapies in the era of personalized medicine

    PubMed Central

    Van Ness, Michael; Gregg, Jeffrey; Wang, Jun

    2012-01-01

    Gastric malignancy constitutes a major cause of cancer deaths worldwide. Despite recent advances in surgical techniques combined with neoadjuvant chemotherapy and radiotherapy approaches, patients with advanced disease still have poor outcomes. An emerging understanding of the molecular pathways that characterize cell growth, cell cycle, apoptosis, angiogenesis, invasion and metastasis has provided novel targets in gastric cancer therapy. In this review, recent advances in the understanding of molecular tumorigenesis for common gastric malignancies are discussed. We also briefly review the current targeted therapies in the treatment of gastric malignancies. Practical insights are highlighted including HER2 testing and target therapy in gastric adenocarcinoma, morphologic features and molecular signatures of imatinib-resistance GISTs, and recent investigations aimed at tumor-specific therapy for neuroendocrine tumors. PMID:22943015

  12. Malignant hyperthermia

    PubMed Central

    Rosenberg, Henry; Davis, Mark; James, Danielle; Pollock, Neil; Stowell, Kathryn

    2007-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene

  13. The importance of lung function, non-malignant diseases associated with asbestos, and symptoms as predictors of ischaemic heart disease in shipyard workers exposed to asbestos.

    PubMed Central

    Sandén, A; Järvholm, B; Larsson, S

    1993-01-01

    The mortality from ischaemic heart disease was studied in a prospective cohort of 1725 shipyard workers exposed to asbestos. The analyses were stratified for age and smoking habits and restricted to men. In agreement with other findings, men with impaired lung function had a significantly higher risk (relative risk (RR) = 3.5) of dying from ischaemic heart disease than men with normal lung function. Men with asbestosis or suspected asbestosis had a significantly higher risk (RR = 3.1) of dying from ischaemic heart disease than men without asbestosis. Thus asbestosis or suspected asbestosis also seemed to be a risk factor for ischaemic heart disease. This finding was independent of respiratory function. There was no increased risk for ischaemic heart disease in men with compared with men without pleural plaques. Men with production of phlegm or sputum and wheezing or whistling had no increased risk for ischaemic heart disease compared with men without these symptoms. In the group with normal lung function men with dyspnoea had a significantly higher risk of dying from ischaemic heart disease than men without dyspnoea. The findings for men with asbestosis or suspected asbestosis indicated a further risk factor besides impaired lung function, in persons exposed to asbestos. Perhaps this risk factor is due to lesions of the pericardium with consequences for heart function. PMID:8398871

  14. Advanced laparoscopic surgery for colorectal disease: NOTES/NOSE or single port?

    PubMed

    Sehgal, Rishabh; Cahill, Ronan A

    2014-02-01

    Laparoscopic surgery for colorectal disease is an evolving, dynamic subject undergoing constant adaptation. Hence there are significant ongoing advances in technique and technology as has been seen with the emergence of single port and Natural Orifice Transluminal Endoscopic operations with already considerable ramifications for many aspects of minimal access surgery. Most recently single port technologies and expertise have synergized with Transanal Endoscopic (TEM/TEO) experience to allow their convergence out of their respective niches so that pelvic surgery can be laparoendoscopically performed from both its abdominal and perineal aspects. Distinct from wound-related benefits, such capacity for high resolution and multi-dimensional imaging relates significant benefit to the operating team and patient. This state of the art review demonstrates the crucial perspective that advanced practices and performance capabilities are intrinsically complimentary rather than competitive. All surgeons need therefore to participate in adapting their practice styles to allow technical step-advance across the discipline.

  15. Low Circulating Levels of Dehydroepiandrosterone in Histologically Advanced Nonalcoholic Fatty Liver Disease

    PubMed Central

    Charlton, Michael; Angulo, Paul; Chalasani, Naga; Merriman, Ralph; Viker, Kimberly; Charatcharoenwitthaya, Phunchai; Sanderson, Schuyler; Gawrieh, Samer; Krishnan, Anuradha; Lindor, Keith

    2010-01-01

    The biological basis of variability in histological progression of nonalcoholic fatty liver disease (NAFLD) is unknown. Dehydroepiandrosterone(DHEA) is the most abundant steroid hormone and has been shown to influence sensitivity to oxidative stress, insulin sensitivity, and expression of peroxisome proliferator-activated receptor alpha and procollagen messenger RNA. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of DHEA. Serum samples were obtained prospectively at the time of liver biopsy in 439 patients with NAFLD (78 in an initial and 361 in validation cohorts) and in controls with cholestatic liver disease (n = 44). NAFLD was characterized as mild [simple steatosis or nonalcoholic steatohepatitis (NASH) with fibrosis stage 0–2] or advanced (NASH with fibrosis stage 3–4). Serum levels of sulfated DHEA (DHEA-S) were measured by enzyme-linked immunosorbent assay. Patients with advanced NAFLD had lower plasma levels of DHEA-S than patients with mild NAFLD in both the initial (0.25 ± 0.07 versus 1.1 ± 0.09 µg/mL, P < 0.001) and validation cohorts (0.47 ± 0.06 versus 0.99 ± 0.04 µg/mL, P < 0.001). A “dose effect” of decreasing DHEA-S and incremental fibrosis stage was observed with a mean DHEA-S of 1.03 ± 0.05, 0.96 ± 0.07, 0.83 ± 0.11, 0.66 ± 0.11, and 0.35 ± 0.06 µg/mL for fibrosis stages 0, 1, 2, 3, and 4, respectively. All patients in both cohorts in the advanced NAFLD group had low DHEA-S levels, with the majority in the hypoadrenal range. The association between DHEA-S and severity of NAFLD persisted after adjusting for age. A relationship between disease/fibrosis severity and DHEA-S levels was not seen in patients with cholestatic liver diseases. Conclusion More advanced NAFLD, as indicated by the presence of NASH with advanced fibrosis stage, is strongly associated with low circulating DHEA-S. These data provide novel evidence for relative DHEA-S deficiency in patients with

  16. Congenital heart disease and rheumatic heart disease in Africa: recent advances and current priorities.

    PubMed

    Zühlke, Liesl; Mirabel, Mariana; Marijon, Eloi

    2013-11-01

    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.

  17. 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.

  18. Advances in Biomedical Imaging, Bioengineering, and Related Technologies for the Development of Biomarkers of Pancreatic Disease: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Biomedical Imaging and Bioengineering Workshop.

    PubMed

    Kelly, Kimberly A; Hollingsworth, Michael A; Brand, Randall E; Liu, Christina H; Singh, Vikesh K; Srivastava, Sudhir; Wasan, Ajay D; Yadav, Dhiraj; Andersen, Dana K

    2015-11-01

    A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Biomedical Imaging and Bioengineering focused on research gaps and opportunities in the development of new biomarkers of pancreatic disease. The session was held on July 22, 2015, and structured into 6 sessions: 1) Introduction and Overview; 2) Keynote Address; 3) New Approaches to the Diagnosis of Chronic Pancreatitis; 4) Biomarkers of Pain and Inflammation; 5) New Approaches to the Detection of Pancreatic Cancer; and 6) Shed Exosomes, Shed Cells, and Shed Proteins. Recent advances in the fields of pancreatic imaging, functional markers of pancreatic disease, proteomics, molecular and cellular imaging, and detection of circulating cancer cells and exosomes were reviewed. Knowledge gaps and research needs were highlighted. The development of new methods for the noninvasive determination of pancreatic pathology; the use of cellular markers of pancreatic function, inflammation, pain, and malignancy; and the refinement of methods to identify cells and cellular constituents of pancreatic cancer were discussed. The further refinement of sophisticated technical methods and the need for clinical studies to validate these new approaches in large-scale studies of patients at risk for the development of pancreatic disease were repeatedly emphasized.

  19. Advances in Biomedical Imaging, Bioengineering, and Related Technologies for the Development of Biomarkers of Pancreatic Disease: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Biomedical Imaging and Bioengineering Workshop

    PubMed Central

    Kelly, Kimberly A.; Hollingsworth, Michael A.; Brand, Randall E.; Liu, Christina H.; Singh, Vikesh K.; Srivastava, Sudhir; Wasan, Ajay D.; Yadav, Dhiraj; Andersen, Dana K.

    2015-01-01

    A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Biomedical Imaging and Bioengineering focused on research gaps and opportunities in the development of new biomarkers of pancreatic disease. The session was held on July 22, 2015, and structured into six sessions: 1) introduction and overview, 2) keynote address, 3) new approaches to the diagnosis of chronic pancreatitis, 4) biomarkers of pain and inflammation, 5) new approaches to the detection of pancreatic cancer, and 6) shed exosomes, shed cells, and shed proteins. Recent advances in the fields of pancreatic imaging, functional markers of pancreatic disease, proteomics, molecular and cellular imaging, and detection of circulating cancer cells and exosomes were reviewed. Knowledge gaps and research needs were highlighted. The development of new methods for the non-invasive determination of pancreatic pathology, the use of cellular markers of pancreatic function, inflammation, pain, and malignancy, and the refinement of methods to identify cells and cellular constituents of pancreatic cancer were discussed. The further refinement of sophisticated technical methods, and the need for clinical studies to validate these new approaches in large-scale studies of patients at risk for the development of pancreatic disease was repeatedly emphasized. PMID:26465948

  20. Biliary atresia and other cholestatic childhood diseases: Advances and future challenges.

    PubMed

    Verkade, Henkjan J; Bezerra, Jorge A; Davenport, Mark; Schreiber, Richard A; Mieli-Vergani, Georgina; Hulscher, Jan B; Sokol, Ronald J; Kelly, Deirdre A; Ure, Benno; Whitington, Peter F; Samyn, Marianne; Petersen, Claus

    2016-09-01

    Biliary Atresia and other cholestatic childhood diseases are rare conditions affecting the function and/or anatomy along the canalicular-bile duct continuum, characterised by onset of persistent cholestatic jaundice during the neonatal period. Biliary atresia (BA) is the most common among these, but still has an incidence of only 1 in 10-19,000 in Europe and North America. Other diseases such as the genetic conditions, Alagille syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC), are less common. Choledochal malformations are amenable to surgical correction and require a high index of suspicion. The low incidence of such diseases hinder patient-based studies that include large cohorts, while the limited numbers of animal models of disease that recapitulate the spectrum of disease phenotypes hinders both basic research and the development of new treatments. Despite their individual rarity, collectively BA and other cholestatic childhood diseases are the commonest indications for liver transplantation during childhood. Here, we review the recent advances in basic research and clinical progress in these diseases, as well as the research needs. For the various diseases, we formulate current key questions and controversies and identify top priorities to guide future research.

  1. Advances in Cardiovascular MRI for Diagnostics: Applications in Coronary Artery Disease and Cardiomyopathies

    PubMed Central

    Salerno, Michael; Kramer, Christopher M

    2010-01-01

    Background Cardiac magnetic resonance (CMR) imaging has emerged as an important cardiac imaging technique for the evaluation of multiple cardiac pathologies. Objective/Method The goal of this review is to describe recent advances in techniques which have extended the potential applications of CMR. The focus will be on the clinical applications of CMR for the evaluation of coronary artery disease and heart failure/cardiomyopathies which are major causes of morbidity and mortality worldwide. Conclusion CMR provides unique tissue characterization which is not available from other imaging modalities and has demonstrated important diagnostic and prognostic information in many forms of heart disease. PMID:21113233

  2. Advanced biomaterials and their potential applications in the treatment of periodontal disease.

    PubMed

    Chen, Xi; Wu, Guofeng; Feng, Zhihong; Dong, Yan; Zhou, Wei; Li, Bei; Bai, Shizhu; Zhao, Yimin

    2016-08-01

    Periodontal disease is considered as a widespread infectious disease and the most common cause of tooth loss in adults. Attempts for developing periodontal disease treatment strategies, including drug delivery and regeneration approaches, provide a useful experimental model for the evaluation of future periodontal therapies. Recently, emerging advanced biomaterials including hydrogels, films, micro/nanofibers and particles, hold great potential to be utilized as cell/drug carriers for local drug delivery and biomimetic scaffolds for future regeneration therapies. In this review, first, we describe the pathogenesis of periodontal disease, including plaque formation, immune response and inflammatory reactions caused by bacteria. Second, periodontal therapy and an overview of current biomaterials in periodontal regenerative medicine have been discussed. Third, the roles of state-of-the-art biomaterials, including hydrogels, films, micro/nanofibers and micro/nanoparticles, developed for periodontal disease treatment and periodontal tissue regeneration, and their fabrication methods, have been presented. Finally, biological properties, including biocompatibility, biodegradability and immunogenicity of the biomaterials, together with their current applications strategies are given. Conclusive remarks and future perspectives for such advanced biomaterials are discussed.

  3. 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

  4. 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.

  5. ATYPICAL MACULOPATHY IN A PATIENT WITH LIGHT CHAIN DEPOSITION DISEASE MIMICKING ADVANCED GEOGRAPHIC ATROPHY

    PubMed Central

    Oshry, Lauren J.; Reichel, Elias

    2017-01-01

    Purpose: To report a previously unreported presentation of advanced geographic atrophy of the macula mimicking nonneovascular (dry) age-related macular degeneration in a patient with light chain deposition disease. Methods: Ocular examination included dilated fundus examination, fundus autofluorescence, full-field electroretinography, and spectral domain optical coherence tomography. Patients: Single-patient case report. Results: Dilated fundus examination demonstrated diffuse loss of the retinal pigment epithelium in a geographic atrophy pattern in the macula and drusenlike deposits localized to the outer retina and retinal pigment epithelium. There were no signs of choroidal neovascularization or retinal pigment epithelium detachments. Fundus autofluorescence demonstrated wide areas of retinal pigment epithelium loss. Full-field electroretinography was normal. Spectral domain optical coherence tomography displayed atrophy of the outer retinal layers. Discussion: This is the first documented case of drusenlike deposits and maculopathy in a patient with light chain deposition disease that mimics advanced geographic atrophy that is typically observed in nonneovascular age-related macular degeneration. Physicians should be aware of the macular changes that can be associated with light chain deposition disease, and patients with light chain deposition disease should be regularly evaluated for associated macular disease. PMID:26934302

  6. Role of laparoscopy in hepatobiliary malignancies

    PubMed Central

    Arumugam, Prabhu; Balarajah, Vickna; Watt, Jennifer; Abraham, Ajit T.; Bhattacharya, Satyajit; Kocher, Hemant M.

    2016-01-01

    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 T2 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Association of mannose-binding lectin levels and invasive fungal disease in hematologic malignancy patients receiving myelosuppressive chemotherapy or allogeneic hematopoietic stem cell transplantation.

    PubMed

    Riwes, M M; Leather, H; Neal, D; Bennett, C; Sugrue, M; Cline, C; Stokes, J; Hiemenz, J; Hsu, J; Wingard, J R

    2016-09-01

    Several studies have suggested an association of mannose-binding lectin (MBL) deficiency with infections. In this study, we investigated the association between MBL deficiency and invasive fungal disease (IFD) in hematologic malignancy patients receiving myelosuppressive chemotherapy or hematopoietic stem cell transplant. MBL levels were quantified at the start of treatment in 152 patients who were followed for 6 months and scored as developing IFD or not. Forty-five patients (29.6%) developed IFD, of which 21 (46.7% of IFD cases and 13.8% of patients) were proven or probable IFD. Fifty-nine (38.8%) had MBL levels <1000 ng/mL. The rates of all IFD in patients with MBL levels below and above 1000 ng/mL were 33.9% and 26.9%, respectively (P=0.356). The rates of proven or probable IFD in patients with MBL levels below and above 1000 ng/mL were 11.9% and 15.1%, respectively (P=0.579). MBL levels <1000 ng/mL were not predictors of death (P=0.233). As expected, IFD was associated with death (P<0.0001). Our findings indicate that MBL levels <1000 ng/mL were not associated with an increased risk of developing IFD or overall survival.

  12. 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...

  13. 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

  14. [Application of levodopa/carbidopa intestinal gel in advanced Parkinson's disease].

    PubMed

    Toth, Adrián; Nagy, Helga; Wacha, Judit; Bereczki, Dániel; Takáts, Annamária

    2015-12-01

    Parkinson's disease is the second most common neurodegenerative disorder around the world. Levodopa has remained the "gold standard" of the therapy even several decades after its introduction. Chronic levodopa treatment is associated with the development of motor complications in most patients. Advanced Parkinson's disease is characterized by these complications: motor and non-motor fluctuation and disturbing dyskinesia. Continuous dopaminergic stimulation might reduce these complications. In advanced Parkinson's disease levodopa is still effective. In the treatment of this stage there are several advanced or device-aided therapies: apomorphine pump, deep brain stimulation and levodopa/carbidopa intestinal gel. Levodopa/carbidopa intestinal gel is an aqueous gel that can be delivered to the jejunum via a percutaneous gastrojejunostomy tube which is connected to an infusion pump dosing the levodopa gel continuously to the place of absorption. Levodopa/carbidopa gel infusion can be used as monotherapy, can be tested, can be used individually and this therapy is reversible. Several clinical trials demonstrated that levodopa/carbidopa intestinal gel therapy is of long-term benefit, improves the quality of life of the patients and can reduce motor fluctuation and dyskinesia.

  15. 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.

  16. ‘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

  17. Malignant Pleural Mesothelioma

    PubMed Central

    Tsao, Anne S.; Wistuba, Ignacio; Roth, Jack A.; Kindler, Hedy Lee

    2009-01-01

    Malignant pleural mesothelioma (MPM) is a deadly disease that occurs in 2,000 to 3,000 people each year in the United States. Although MPM is an extremely difficult disease to treat, with the median overall survival ranging between 9 and 17 months regardless of stage, there has been significant progress over the last few years that has reshaped the clinical landscape. This article will provide a comprehensive discussion of the latest developments in the treatment of MPM. We will provide an update of the major clinical trials that impact mesothelioma treatment in the resectable and unresectable settings, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. In addition, there are controversial issues, such as the role of extrapleural pneumonectomy, adjuvant radiotherapy, and use of intensity-modulated radiotherapy versus hemithoracic therapy that will also be addressed in this manuscript. PMID:19255316

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. The role of single-photon emission computed tomography/computed tomography in benign and malignant bone disease.

    PubMed

    Horger, Marius; Bares, Roland

    2006-10-01

    Radiological (plain radiographs, computed tomography [CT], magnetic resonance imaging [MRI]) and nuclear medicine methods (bone scan, leukocyte scan) both provide unique information about the status of the skeleton. Both have typical strengths and weaknesses, which often lead to the sequential use of different procedures in daily routine. This use causes the unnecessary loss of time and sometimes money, if redundant information is obtained without establishing a final diagnosis. Recently, new devices for hybrid imaging (single-photon emission computed tomography/computed tomography [SPECT/CT], positron emission tomography/computed tomography [PET/CT]) were introduced, which allow for direct fusion of morphological (CT) and functional (SPECT, PET) data sets. With regard to skeletal abnormalities, this approach appears to be extremely useful because it combines the advantages of both techniques (high-resolution imaging of bone morphology and high sensitivity imaging of bone metabolism). By the accurate correlation of both, a new quality of bone imaging has now become accessible. Although researchers undertaking the initial studies exclusively used low-dose CT equipment, a new generation of SPECT/CT devices has emerged recently. By integrating high-resolution spiral CT, quality of bone imaging may improve once more. Ongoing prospective studies will have to show whether completely new diagnostic algorithms will come up for classification of bone disease as a consequence of this development. Besides, the role of ultrasonography and MRI for bone and soft-tissue imaging also will have to be re-evaluated. Looking at the final aim of all imaging techniques--to achieve correct diagnosis in a fast, noninvasive, comprehensive, and inexpensive way--we are now on the edge of a new era of multimodality imaging that will probably change the paths and structure of medicine in many ways. Presently, hybrid imaging using SPECT/CT has been proven to increase sensitivity and specificity

  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. Low vitamin D status is associated with advanced liver fibrosis in patients with nonalcoholic fatty liver disease.

    PubMed

    Yang, Bing-Bing; Chen, Yuan-Hua; Zhang, Cheng; Shi, Chang-E; Hu, Kai-Feng; Zhou, Ju; Xu, De-Xiang; Chen, Xi

    2017-02-01

    Several studies explored the association between vitamin D status and nonalcoholic fatty liver disease with contradictory results. We aimed to investigate the association between vitamin D status, inflammatory cytokines and liver fibrosis in nonalcoholic fatty liver disease patients. Two hundred nineteen nonalcoholic fatty liver disease patients and 166 age- and gender- matched healthy controls were recruited for this study. Serum 25(OH)D was measured by radioimmunoassay. Serum interleukin-8 and transforming growth factor-β1 were measured using ELISA. Serum 25(OH)D was only marginally decreased in nonalcoholic fatty liver disease patients. Interestingly, serum 25(OH)D was markedly reduced in nonalcoholic fatty liver disease patients with advanced liver fibrosis compared to nonalcoholic fatty liver disease patients with indeterminate liver fibrosis and no advanced fibrosis. Logistic regression analysis showed that there was an inverse association between serum 25(OH)D and severity of liver fibrosis in nonalcoholic fatty liver disease patients. Further analysis showed that serum interleukin-8 was elevated in nonalcoholic fatty liver disease patients, the highest interleukin-8 in patients with advanced fibrosis. An inverse correlation between serum 25(OH)D and interleukin-8 was observed in nonalcoholic fatty liver disease patients with and without liver fibrosis. Although serum transforming growth factor-β1 was slightly elevated in nonalcoholic fatty liver disease patients, serum transforming growth factor-β1 was reduced in nonalcoholic fatty liver disease patients with advanced fibrosis. Unexpectedly, a positive correlation between serum 25(OH)D and transforming growth factor-β1 was observed in nonalcoholic fatty liver disease patients with advanced fibrosis. In conclusion, low vitamin D status is associated with advanced liver fibrosis in nonalcoholic fatty liver disease patients. Interleukin-8 may be an important mediator for hepatic fibrosis in nonalcoholic

  5. Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications

    PubMed Central

    Weidemann, F; Niemann, M; Störk, S; Breunig, F; Beer, M; Sommer, C; Herrmann, S; Ertl, G; Wanner, C

    2013-01-01

    Objective The long-term effects of enzyme-replacement therapy (ERT) in Fabry disease are unknown. Thus, the aim of this study was to determine whether ERT in patients with advanced Fabry disease affects progression towards ‘hard’ clinical end-points in comparison with the natural course of the disease. Methods A total of 40 patients with genetically proven Fabry disease (mean age 40 ± 9 years; n = 9 women) were treated prospectively with ERT for 6 years. In addition, 40 subjects from the Fabry Registry, matched for age, sex, chronic kidney disease stage and previous transient ischaemic attack (TIA), served as a comparison group. The main outcome was a composite of stroke, end-stage renal disease (ESRD) and death. Secondary outcomes included changes in myocardial left ventricular (LV) wall thickness and replacement fibrosis, change in glomerular filtration rate (GFR), new TIA and change in neuropathic pain. Results During a median follow-up of 6.0 years (bottom and top quartiles: 5.1, 7.2), 15 events occurred in 13 patients (n = 7 deaths, n = 4 cases of ESRD and n = 4 strokes). Sudden death occurred (n = 6) only in patients with documented ventricular tachycardia and myocardial replacement fibrosis. The annual progression of myocardial LV fibrosis in the entire cohort was 0.6 ± 0.7%. As a result, posterior end-diastolic wall thinning was observed (baseline, 13.2 ± 2.0 mm; follow-up, 11.4 ± 2.1 mm; P < 0.01). GFR decreased by 2.3 ± 4.6 mL min−1 per year. Three patients experienced a TIA. The major clinical symptom was neuropathic pain (n = 37), and this symptom improved in 25 patients. The event rate was not different between the ERT group and the untreated (natural history) group of the Fabry Registry. Conclusion Despite ERT, clinically meaningful events including sudden cardiac death continue to develop in patients with advanced Fabry disease. PMID:23586858

  6. [Advance in application of syndromic surveillance for detection of emerging infectious diseases and outbreak alerts].

    PubMed

    Lin, Mei; Wang, Xin; Liang, Dabin

    2015-07-01

    Over the past decade, syndromic surveillance, as supplementation of disease surveillance, has provided possibility of early alert in a real-time way for detection of emerging infectious diseases and outbreaks of widespread infectious diseases, resulting in improvement in sensitivity of outbreak detection and public health alert capacity. This tool has been highly valued and widely used in the world, and effective implementation has been observed in China. Upon abundant literature search, the authors reviewed the progress and advance of syndromic surveillance in early alert of emerging infectious diseases and outbreaks, and analyzed the problem met in the current situation in China when implementing syndromic surveillance in local facilities, which are high cost, lack of medical information platform, lack of real-time digital alert system and lack of a comprehensive information exchange platform. The authors suggested that syndromic surveillance should be implemented considering the local situation and performed in a more effective way in the current situation. Syndromic surveillance has to be integrated into the conventional public health surveillance systems and advanced laboratory networks. Digital information system is urgently needed to achieve real-time alert.

  7. Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson's Disease

    ClinicalTrials.gov

    2017-02-22

    Idiopathic Parkinson's Disease; Parkinson's Disease; Basal Ganglia Disease; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Nervous System Diseases; Neurodegenerative Diseases; Parkinsonian Disorders

  8. 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

  9. 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

  10. Treatment of Parkinson disease: a 64-year-old man with motor complications of advanced Parkinson disease.

    PubMed

    Tarsy, Daniel

    2012-06-06

    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.

  11. Diagnosis and management options in malignant pleural effusions

    PubMed Central

    Dixit, Ramakant; Agarwal, KC; Gokhroo, Archana; Patil, Chetan B; Meena, Manoj; Shah, Narender S; Arora, Piyush

    2017-01-01

    Malignant pleural effusion (MPE) denotes an advanced malignant disease process. Most of the MPE are metastatic involvement of the pleura from primary malignancy at lung, breast, and other body sites apart from lymphomas. The diagnosis of MPE has been traditionally made on cytological examination of pleural fluid and/or histological examination of pleural biopsy tissue that still remains the initial approach in these cases. There has been tremendous advancement in the diagnosis of MPE now a day with techniques i.e. characteristic Ultrasound and computed tomography features, image guided biopsies, fluorodeoxyglucose-positron emission tomography imaging, thoracoscopy with direct biopsy under vision, tumor marker studies and immunocytochemical analysis etc., that have made possible an early diagnosis of MPE. The management of MPE still remains a challenge to pulmonologist and oncologist. Despite having various modalities with better tolerance such as pleurodesis and indwelling pleural catheters etc., for long-term control, all the management approaches remain palliative to improve the quality of life and reduce symptoms. While choosing an appropriate management intervention, one should consider the clinical status of the patient, life expectancy, overall cost, availability and comparative institutional outcomes, etc. PMID:28360465

  12. 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

  13. Kienböck Disease: Recent Advances in the Basic Science, Assessment and Treatment.

    PubMed

    Bain, Gregory Ian; Yeo, Chong Jin; Morse, Levi Philip

    2015-10-01

    Kienböck disease is a disorder of impaired lunate vascularity which ultimately has the potential to lead to marked degeneration of the wrist and impaired wrist function. The aetiology of the avascular necrosis is uncertain, but theories relate to ulnar variance, variability in lunate vascularity and intraosseous pressures. Clinical symptoms can be subtle and variable, requiring a high index of suspicion for the diagnosis. The Lichtmann classification has historically been used to guide management. We present a review of Kienböck disease, with a focus on the recent advances in assessment and treatment. Based on our understanding thus far of the pathoanatomy of Kienböck's disease, we are proposing a pathological staging system founded on the vascularity, osseous and chondral health of the lunate. We also propose an articular-based approach to treatment, with an arthroscopic grading system to guide management.

  14. 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

  15. Palliative care in pediatric patients with hematologic malignancies.

    PubMed

    Humphrey, Lisa; Kang, Tammy I

    2015-01-01

    Children with advanced cancer, including those with hematologic malignancies, can benefit from interdisciplinary palliative care services. Palliative care includes management of distressing symptoms, attention to psychosocial and spiritual needs, and assistance with navigating complex medical decisions with the ultimate goal of maximizing the quality-of-life of the child and family. Palliative care is distinct from hospice care and can assist with the care of patients throughout the cancer continuum, irrespective of prognosis. While key healthcare organizations, including the Institute of Medicine, the American Academy of Pediatrics and the American Society of Clinical Oncology among many others endorse palliative care for children with advanced illness, barriers to integration of palliative care into cancer care still exist. Providing assistance with advance care planning, guiding patients and families through prognostic uncertainty, and managing transitions of care are also included in goals of palliative care involvement. For patients with advanced malignancy, legislation, included in the Patient Protection and Affordable Health Care Act allows patients and families more options as they make the difficult transition from disease directed therapy to care focused on comfort and quality-of-life.

  16. Advanced glycation end-products produced systemically and by macrophages: A common contributor to inflammation and degenerative diseases.

    PubMed

    Byun, Kyunghee; Yoo, YongCheol; Son, Myeongjoo; Lee, Jaesuk; Jeong, Goo-Bo; Park, Young Mok; Salekdeh, Ghasem Hosseini; Lee, Bonghee

    2017-02-13

    Advanced glycation end products (AGEs) and their receptor have been implicated in the progressions of many intractable diseases, such as diabetes and atherosclerosis, and are also critical for pathologic changes in chronic degenerative diseases, such as Alzheimer's disease, Parkinson's disease, and alcoholic brain damage. Recently activated macrophages were found to be a source of AGEs, and the most abundant form of AGEs, AGE-albumin excreted by macrophages has been implicated in these diseases and to act through common pathways. AGEs inhibition has been shown to prevent the pathogenesis of AGEs-related diseases in human, and therapeutic advances have resulted in several agents that prevent their adverse effects. Recently, anti-inflammatory molecules that inhibit AGEs have been shown to be good candidates for ameliorating diabetic complications as well as degenerative diseases. This review was undertaken to present, discuss, and clarify current understanding regarding AGEs formation in association with macrophages, different diseases, therapeutic and diagnostic strategy and links with RAGE inhibition.

  17. 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

  18. 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.

  19. 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.

  20. TNF-α and Tumor Lysate Promote the Maturation of Dendritic Cells for Immunotherapy for Advanced Malignant Bone and Soft Tissue Tumors

    PubMed Central

    Miwa, Shinji; Nishida, Hideji; Tanzawa, Yoshikazu; Takata, Munetomo; Takeuchi, Akihiko; Yamamoto, Norio; Shirai, Toshiharu; Hayashi, Katsuhiro; Kimura, Hiroaki; Igarashi, Kentaro; Mizukoshi, Eishiro; Nakamoto, Yasunari; Kaneko, Shuichi; Tsuchiya, Hiroyuki

    2012-01-01

    Background Dendritic cells (DCs) play a pivotal role in the immune system. There are many reports concerning DC-based immunotherapy. The differentiation and maturation of DCs is a critical part of DC-based immunotherapy. We investigated the differentiation and maturation of DCs in response to various stimuli. Methods Thirty-one patients with malignant bone and soft tissue tumors were enrolled in this study. All the patients had metastatic tumors and/or recurrent tumors. Peripheral blood mononuclear cells (PBMCs) were suspended in media containing interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF). These cells were then treated with or without 1) tumor lysate (TL), 2) TL + TNF-α, 3) OK-432. The generated DCs were mixed and injected in the inguinal or axillary region. Treatment courses were performed every week and repeated 6 times. A portion of the cells were analyzed by flow cytometry to determine the degree of differentiation and maturation of the DCs. Serum IFN-γ and serum IL-12 were measured in order to determine the immune response following the DC-based immunotherapy. Results Approximately 50% of PBMCs differentiated into DCs. Maturation of the lysate-pulsed DCs was slightly increased. Maturation of the TL/TNF-α-pulsed DCs was increased, commensurate with OK-432-pulsed DCs. Serum IFN-γ and serum IL-12 showed significant elevation at one and three months after DC-based immunotherapy. Conclusions Although TL-pulsed DCs exhibit tumor specific immunity, TL-pulsed cells showed low levels of maturation. Conversely, the TL/TNF-α-pulsed DCs showed remarkable maturation. The combination of IL-4/GM-CSF/TL/TNF-α resulted in the greatest differentiation and maturation for DC-based immunotherapy for patients with bone and soft tissue tumors. PMID:23300824

  1. 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

  2. Advances in the Development of Disease-Modifying Treatments for Amyotrophic Lateral Sclerosis.

    PubMed

    Moujalled, Diane; White, Anthony R

    2016-03-01

    Amyotrophic lateral sclerosis (ALS) is a progressive adult-onset, neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. Over recent years, numerous genes ha ve been identified that promote disease pathology, including SOD1, TARDBP, and the expanded hexanucleotide repeat (GGGGCC) within C9ORF72. However, despite these major advances in identifying genes contributing to ALS pathogenesis, there remains only one currently approved therapeutic: the glutamate antagonist, riluzole. Seminal breakthroughs in the pathomechanisms and genetic factors associated with ALS have heavily relied on the use of rodent models that recapitulate the ALS phenotype; however, while many therapeutics have proved to be significant in animal models by prolonging life and rescuing motor deficits, they have failed in human clinical trials. This may be due to fundamental differences between rodent models and human disease, the fact that animal models are based on overexpression of mutated genes, and confounding issues such as difficulties mimicking the dosing schedules and regimens implemented in mouse models to humans. Here, we review the major pathways associated with the pathology of ALS, the rodent models engineered to test efficacy of candidate drugs, the advancements being made in stem cell therapy for ALS, and what strategies may be important to circumvent the lack of successful translational studies in the clinic.

  3. Clinical and Genetic Advances in Paget's Disease of Bone: a Review.

    PubMed

    Alonso, N; Calero-Paniagua, I; Del Pino-Montes, J

    2017-01-01

    Paget's disease of bone (PDB) is the second most common metabolic bone disorder, after osteoporosis. It is characterised by focal areas of increased and disorganised bone turnover, coupled with increased bone formation. This disease usually appears in the late stages of life, being slightly more frequent in men than in women. It has been reported worldwide, but primarily affects individuals of British descent. Majority of PDB patients are asymptomatic, but clinical manifestations include pain, bone deformity and complications, like pathological fractures and deafness. The causes of the disease are poorly understood and it is considered as a complex trait, combining genetic predisposition with environmental factors. Linkage analysis identified SQSTM1, at chromosome 5q35, as directly related to the disease. A number of mutations in this gene have been reported, pP392L being the most common variant among different populations. Most of these variants affect the ubiquitin-associated (UBA) domain of the protein, which is involved in autophagy processes. Genome-wide association studies enlarged the number of loci associated with PDB, and further fine-mapping studies, combined with functional analysis, identified OPTN and RIN3 as causal genes for Paget's disease. A combination of risk alleles identified by genome-wide association studies led to the development of a score to predict disease severity, which could improve the management of the disease. Further studies need to be conducted to elucidate other important aspects of the trait, such as its focal nature and the epidemiological changes found in some populations. In this review, we summarize the clinical characteristics of the disease and the latest genetic advances to identify susceptibility genes. We also list current available treatments and prospective options.

  4. Canine olfactory detection of malignant melanoma

    PubMed Central

    Campbell, Leon Frederick; Farmery, Luke; George, Susannah Mary Creighton; Farrant, Paul B J

    2013-01-01

    Our patient is a 75-year-old man who presented after his pet dog licked persistently at an asymptomatic lesion behin