PRIMARY OBJECTIVES: I. To determine the maximally tolerated dose (MTD) of ATM (gold sodium thiomalate) plus sirolimus. SECONDARY OBJECTIVES: I. To describe the adverse event profile associated with this treatment combination. II. To preliminarily evaluate the response rate, time to progression, progression-free survival and overall survival of patients treated with this treatment combination. TERTIARY OBJECTIVES: I. To evaluate tumor biomarkers of protein kinase C (PKCι) and mammalian Target Of Rapamycin (mTOR) signaling activity as predictors of response to ATM/sirolimus therapy. II. To evaluate the use of surrogate biomarkers of PKCι and mTOR inhibition in peripheral blood lymphocytes (PBLs) to monitor response to ATM/sirolimus therapy. OUTLINE: This is a dose-escalation study. Patients receive sirolimus orally (PO) once daily (QD) on days 1-28 and gold sodium thiomalate intramuscularly (IM) on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or ...
PRIMARY OBJECTIVES: I. To determine the maximally tolerated dose (MTD) of ATM (gold sodium thiomalate) plus sirolimus. SECONDARY OBJECTIVES: I. To describe the adverse event profile associated with this treatment combination. II. To preliminarily evaluate the response rate, time to progression, progression-free survival and overall survival of patients treated with this treatment combination. TERTIARY OBJECTIVES: I. To evaluate tumor biomarkers of protein kinase C (PKCι) and mammalian Target Of Rapamycin (mTOR) signaling activity as predictors of response to ATM/sirolimus therapy. II. To evaluate the use of surrogate biomarkers of PKCι and mTOR inhibition in peripheral blood lymphocytes (PBLs) to monitor response to ATM/sirolimus therapy. OUTLINE: This is a dose-escalation study. Patients receive sirolimus orally (PO) once daily (QD) on days 1-28 and gold sodium thiomalate intramuscularly (IM) on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or ...
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Sodium aurothiomalate (INN, known in the United States as gold sodium thiomalate) is a gold compound that is used for its immunosuppressive anti-rheumatic effects. Along with an orally-administered gold salt, auranofin, it is one of only two gold compounds currently employed in modern medicine. It is primarily given once or twice weekly by intramuscular injection for moderate-severe rheumatoid arthritis although it has also proven itself effective in treating tuberculosis. Its most common side effects are digestive (mostly dyspepsia, mouth swelling, nausea, vomiting and taste disturbance), vasomotor (mostly flushing, fainting, dizziness, sweating, weakness, palpitations, shortness of breath and blurred vision) or dermatologic (usually itchiness, rash, local irritation near to the injection site and hair loss) in nature, although conjunctivitis, blood dyscrasias, kidney damage, joint pain, muscle aches/pains and liver dysfunction are also common. Less commonly, it can cause GI bleeds, dry mucous ...
Comment: The publication reports results that were obtained using a mouse model. The News Release states that a Phase I clinical trial is under way at the Mayo Clinic, but this trial isnt mentioned in the full text of the publication in Cancer Research. According to MedicineNet.com, aurothiomalate is a "gold-containing chemical (salt) used in treating rheumatoid arthritis ...
Consumer Medicine InformationWhat is in this leafletThis leaflet answers some common questions about Myocrisin.It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist. All medicines have risks and benefits. Your doctor has weighed the risks of you being given this medicine against the benefits they expect it will have for you. If you have any concerns about being given this medicine, ask your doctor or pharmacist.Keep this leaflet with..
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Freshly isolated peripheral blood mononuclear cells (PBMC) from 10 healthy volunteers, 28 patients with rheumatoid arthritis (RA), eight patients with osteoarthritis, and five patients with ankylosing spondylitis were examined for interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) production using monoclonal antibodies and an indirect immunofluorescent method. In freshly isolated PBMC from healthy controls very few cells were stained for either IL-1 type. All 20 RA patients who were not receiving parenteral gold therapy had PBMC staining for IL-1 alpha. In these patients, up to 7.5% of PBMC showed bright IL-1 alpha staining (range 1.2-7.5%). No IL-1 beta staining was seen. These IL-1 alpha-staining cells had a dendritic morphology and the percentage of cells staining correlated well with levels of C-reactive protein, an index of disease activity in these RA patients. Significantly fewer IL-1 alpha-staining cells were present in the peripheral blood of RA patients receiving gold therapy
Researchers at the Mayo Clinic have found that protein kinase C-iota (PKCi), an oncogene known to be important in colon and lung cancers, is over-produced in pancreatic cancer and is linked to poor patient survival. They also found that genetically inhibiting PKCi in laboratory animals led to a significant decrease in pancreatic tumor growth and spread. The scientists said that their results strongly indicate that PKCi will be an effective target for pancreatic cancer therapy. The discovery is especially encouraging, they said, because an experimental agent that targets PKCi is already being tested in patients at the Mayo Clinic for other indications. "This is the first study to establish a role for PKCi in growth of pancreatic cancer, so it is exciting to know that an agent already exists that targets PKCi which we can now try in preclinical studies," said the studys senior investigator, Dr. Nicole Murray, of the Mayo Clinics Department of Cancer Biology. The drug, aurothiomalate, which was ...
Gold shimmers, attracts and has always been relatively expensive. This led people to believe that it must have mystical curative properties. Gold therapy was popular. It was given for arthritis, psoriasis, asthma and sexually transmitted diseases in the form of orally administered gold salts. It was and is still used in several ancient systems of medicine.Gold therapy is effective in rheumatoid arthritis. Eventually, as scientific evidence-based medicine gained popularity, the use of gold fell into disrepute. It did not work in all forms of arthritis. It had no effect on some of the other diseases mentioned. In fact, unless the dosage was carefully controlled, gold accumulated in the body and produced itching, skin pigmentation, pneumonia, jaundice and kidney failure. Today, however, the use of gold has resurged and it is effective when used in rheumatoid arthritis (RA).. Some 10 million Indians, 70 per cent of whom are women between the ages 30 and 50, are affected by RA. The disease strikes ...
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The effect of therapeutic concentrations of D-penicillamine, sodium aurothiomalate, and levamisole on in vitro neutrophil chemotaxis and random migration in normal subjects and patients with rheumatoid arthritis was studied. D-penicillamine produced no changes. Sodium aurothiomalate produced dose-related reductions in chemotaxis in normal subjects and in patients who had a good clinical response to gold therapy, while patients who had failed to respond to gold showed a minimal nondose dependent reduction. Levamisole produced dose-dependent stimulation of chemotaxis, a greater effect found with the patients cells. Neutrophil chemotaxis improved to normal values in most patients responding to several months of D-penicillamine treatment but showed an immediate and marked stimulation in patients treated with levamisole. ...
Seventy-four Israeli patients with rheumatoid arthritis (RA) were studied for possible association between HLA antigens and adverse reactions to gold treatment (aurothioglucose). HLA-B35 was significantly increased in patients who developed gold induced mucocutaneous lesions. These results are in accord with earlier reports, despite the different genetic background of the Israeli RA population and the different type of gold compound used. ...
We describe the first case of chronic neutropenia of 17 years duration following gold therapy in a 53-year-old woman given a 1-g course of gold therapy in 1965 for treatment of seropositive rheumatoid arthritis. Although she had a good response to the gold therapy, her originally normal leukocyte count fell to 1.2 x 10(9)/L. Over the subsequent 17 years, she required multiple hospitalizations for recurrent skin, mouth, and respiratory tract infections. Serial leukocyte counts failed to show a cyclical nature to the chronic neutropenia. Normal results of a technetium Tc 99m spleen scan and lack of increased bone marrow leukocyte precursors rendered a diagnosis of Feltys syndrome unlikely. A bone marrow biopsy specimen revealed an isolated reduction in the number of myeloid precursors, which is consistent with gold-induced bone marrow toxicity. This patients relative freedom from serious life-threatening infections remains enigmatic, but is undoubtedly related to her ability to augment another ...
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The book The Essential Guide to Planning Law: Decision-Making and Practice in the UK, Adam Sheppard, Deborah Peel, Heather Ritchie, and Sophie Berry is published by Policy Press at the University of Bristol.
... looks at the story of Rebecca Latimer Felton, who at the age of 87 became the first woman to serve in the Untitled States senate. While she only served for one day, she led the way for greater representation of women in the senate. While I was racing through the tunnels that link the concourses at Atlantas […]. ...
Dennis Ritchie was a computer scientist who wrote the popular C programming language and helped develop the Unix operating system.
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Eldest son of Hugh Wallace of Biscany the younger and his wife Frances, second daughter of James Ritchie of Busbie and Craigton. Inherited his fathers share of Biscany estate in St Elizabeth, Jamaica, in 1800.. Born 03/11/1789. Lieutenant in the 7th Royal Fusileers. Died at Auxerre in France c. 1870, unmarried.. ...
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TY - GEN. T1 - (111)-Oriented large-grain Ge on insulator by gold-induced crystallization combined with interfacial layer insertion. AU - Park, Jong Hyeok. AU - Suzuki, Tsuneharu. AU - Kurosawa, Masashi. AU - Miyao, Masanobu. AU - Sadoh, Taizoh. PY - 2012/10/31. Y1 - 2012/10/31. N2 - Low-temperature (≤ 350°C) formation of orientation-controlled large-grain Ge on insulating substrates is essential to achieve advanced flexible devices employing plastic substrates. To achieve this, effects of interfacial-oxide layer insertion on gold-induced crystallization (GIC) of amorphous Ge films on insulating substrates have been investigated. Consequently, (111)-oriented large-grain (20-50 μm) Ge crystals are obtained at 350°C by inserting interfacial oxide layers. It is speculated that this phenomena is attributed to suppression of random bulk nucleation of Ge in Au films.. AB - Low-temperature (≤ 350°C) formation of orientation-controlled large-grain Ge on insulating substrates is essential to ...
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Rheumatoid arthritis is a painful and debilitating inflammatory disorder with no known cure. It has been hypothesised that targeting the activity of RHO family proteins might be an effective therapeutic strategy, as these proteins are required for the function of macrophages, which contribute to immunopathology in arthritic joints. However, this notion is challenged in a recent paper by Khan et al. Unexpectedly, mice deficient for a key RHO-activating enzyme, geranylgeranyltransferase type I (GGTase-I), specifically in macrophages were found to develop spontaneous and severe joint inflammation resembling erosive rheumatoid arthritis. Macrophage-specific deficiency in GGTase-I was sufficient to induce pro-inflammatory signalling pathways and initiate the disease owing to sustained activation of RHO family proteins in macrophages. These data indicate that GGTase-I is not essential for the activity of RHO family proteins, and that inhibition of this enzyme can worsen, rather than prevent, the ...
If rheumatoid arthritis is ever to be controlled completely and permanently, it would seem reasonable to suppose that such a result would have to be achieved during the comparatively early stages of the disease; that is, before marked crippling caused by joint destruction, ankylosis and deformity has taken place. In the early months of rheumatoid arthritis, apparently up to one year, the disease is nearly always completely reversible. It may be completely reversible even later if joint destruction has not occurred. This characteristic of rheumatoid arthritis has been stressed recently by Hench in his Heberden Oration.1. Much has been written ...
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Make a difference, no matter how big or small.. It is a motto for Penticton Secondary School student Victoria Ritchies life.. "I really like giving back. I love this community and all it has given me over the years. I share my voice in many areas as I feel it is important youth be involved in decision-making in our community." said Ritchie.. Ritchie, who was chosen as the Rotary Club of Penticton-Okanagan student of the month, enjoys volunteering whether it is weekly at the local hospital, with the Special Olympic swimming team every Saturday, as the youth voice on the executive board of First Things First South Okanagan, or on the steering committee of the Youth Engagement Strategy, she wants to make a difference.. Read more: Penticton youth raise their voices with YES Project. "Victoria is an altruistic, diligent, courageous, positive and humble person. In my 30 years as an educator, I have never known a student who has given so much to her school, community and the world. She is our top ...
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