Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV-1-related neurological diseases, excluding opportunistic infections and HIV encephalitis, are considered here. Most occur in severely immunosuppressed patients, with CD4 counts of under 200 x 10(6) l-1. Primary brain lymphoma and metastases from systemic non-Hodgkin's lymphoma, the second commonest cause of cerebral mass lesions in AIDS, are usually aggressive B cell tumours. Their poor median survival after treatment, compared with that of lymphomas in non-AIDS patients, seems related to systemic complications, particularly opportunistic infections. Kaposi's sarcoma produces neurological symptoms exceptionally. Cerebral infarction is often unrecognized clinically but large vessel arteritic occlusions may occur. Intracranial haemorrhages occur mostly in thrombocytopenic patients. Seizures are frequently referred to the neurologist; investigation may lead to a diagnosis of AIDS. Nearly 50% of patients with seizures have cerebral toxoplasmosis or cryptococcal meningitis; HIV-1 encephalitis is presumed to be the cause in 30%. A subacute or chronic vacuolar myelopathy with pyramidal and posterior column signs is the commonest form of spinal cord involvement in AIDS; its cause remains unknown. Peripheral nerve syndromes occur at all stages of HIV-1 infection. Distal symmetrical peripheral neuropathies are the most frequent, particularly a painful form with axonal atrophy, associated with CMV infection, and seen during ARC or AIDS. Mononeuritis multiplex due to vasculitis, CMV, or lymphoma and a serious lumbosacral polyradiculopathy due to CMV are infrequent. The commonest myopathy is due to zidovudine (AZT); it usually responds to drug withdrawal. The nature, prognosis and optimal management of most other myopathies is yet to be determined.
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PMID:Other neurological diseases in HIV-1 infection: clinical aspects. 134 49

As patients with human immunodeficiency virus infection live longer because of better antiretroviral therapy and infection prophylaxis, the incidence of non-Hodgkin's lymphoma has increased. The risk increases inversely with CD4 count--the most widely used surrogate marker for progressive immune suppression. Zidovudine itself does not appear to be a risk factor. Patients frequently present with extranodal advanced disease. The central nervous system is the primary site in 10% to 20% of cases. Important prognostic factors are performance status, a prior history of acquired immunodeficiency syndrome, and bone marrow involvement. Therapy is complicated by underlying immunosuppression, opportunistic infection, and poor bone marrow reserve. Progress has been made using colony-stimulating factors and less intensive chemotherapy regimens in systemic non-Hodgkin's lymphoma. Treatment of primary central nervous system lymphoma with radiation therapy has not improved survival.
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PMID:Clinical aspects of human immunodeficiency virus-related lymphoma. 145 4

Therapy of AIDS comprises two aspects: (1) causative therapy, directed against HIV, and (2) symptomatic therapy of opportunistic infections and malignancies. The best results regarding antiretroviral therapy - both in vitro and in vivo - have been obtained, so far, with inhibitors of reverse transcriptase. We discuss the mechanism of action, the efficacy, and the side effects of AZT, a nucleoside analogue, and comment on combined therapies with acyclovir and immunomodulators. We report on the therapy of the most frequent opportunistic infection - i.e. Pneumocystis carinii pneumonia - with sulfamethoxazole/trimethoprim and pentamidine as well as the chemoprophylaxis of this disease. During the last few years, important progress has been made in the field of antiviral chemotherapy (HSV, CMV, VZV) and the therapy of gastrointestinal infections. Moreover, the therapy of Kaposi's sarcoma associated with AIDS and that of non-Hodgkin's lymphoma has been established by now.
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PMID:[AIDS therapy]. 220 64

Eleven (50%) of 22 HIV-seropositive patients suffering from congenital coagulation defects and followed at the Hemophilia Center of Padua met the eligibility criteria for zidovudine (AZT) therapy. A 3-year clinical and laboratory follow up is described. Mean length of AZT treatment was 14.3 +/- 11 months. Three patients were enrolled at the latest stages (CDC stage IV) of HIV disease. They showed no clinical improvement after AZT administration and died with AIDS. One CDC stage III patient died from a high-grade non-Hodgkin's lymphoma (NHL) which suddenly developed 3 months after starting AZT. Seven patients began antiretroviral treatment when they were mild or asymptomatic for HIV infection (CDC stage II and III). None developed any sign of HIV disease progression on the basis of CDC criteria. Moreover, AZT administration induced an improvement of the humoral markers related to HIV disease, as CD4 T-lymphocyte count, serum beta 2-microglobulin (B2M) and, although only for few months, neopterin (Np) levels. A mild thrombocytopenia due to HIV infection was detected in 5 patients. In all cases AZT treatment was effective in increasing and/or normalizing the platelet count. Reduced daily dose AZT (600-500 mg/day) appeared to be well tolerated and of minimal toxicity as compared to the higher dose (1200 mg/day). In our study, the zidovudine-induced bone marrow suppression, namely severe anemia or pancytopenia, was the major side-effect limiting tolerance of the higher dose AZT.
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PMID:Report on a 3-year follow-up zidovudine (AZT) treatment in a group of HIV-positive patients with congenital clotting disorders. 795 71

About twenty years ago, the leaders of the National Cancer Institute (NCI) decided to start a new branch in the Clinical Oncology Program of the Division of Cancer Treatment. That new entity was named the Clinical Pharmacology Branch (CPB), and its first leader was a brilliant, young, promising investigator named Bruce A. Chabner. Chabner was educated at Yale and Harvard, and appeared to have an extraordinary grasp of novel concepts that were being developed in the emerging area of cancer chemotherapy. What the NCI leaders did not fully appreciate at the time was that they had just given birth to one of the most extraordinary careers in academic medicine. From the early seventies through the early eighties, Bruce Chabner developed a strong laboratory program that was based on scientific discovery and on the development of new talent. The CPB focused on new drug development, elucidation of drug mechanism(s) of action, and the development of new ways to use drugs that were already available. Concurrent with this laboratory effort was active participation in the development of clinical treatment regimens for Hodgkin's disease, non-Hodgkin's lymphoma, and other malignancies. Individuals who trained under Chabner are now cancer center directors, department heads, laboratory chiefs, and hold many other high-profile positions. From 1981 to 1995 Bruce Chabner was Director of the Division of Cancer Treatment (DCT) of the NCI. In that capacity he was Scientific Director of the Intramural Program within DCT, and he had oversight responsibility for the direction of extramural studies that were funded through the NCI, which were focused on the development of new treatments for human malignant disease. The NCI has five divisions for which the NCI Director has ultimate responsibility. While working with one NCI Director from 1981 to 1988, and with another from 1988 to 1995, and during the transition year of 1988, Bruce Chabner provided stability for the DCT while many changes were occurring throughout the five divisions of the NCI. How does one assess the impact of a career on a discipline such as cancer treatment? It's not easy! Each of the articles contributed to this tribute were written by a person who trained directly with Bruce Chabner, or was otherwise directly impacted by Bruce's guidance. As can be seen from the list of contributors to these Proceedings, each individual has made major contributions to the area of cancer treatment in his or her own right. However, Bruce's contribution to cancer treatment goes far beyond the individuals he trained. The many thousands of human lives who have benefited from his efforts cannot be accurately estimated, because his contributions have been so wide-ranging, as indicated below. Being "Scientific Director" is similar in a number of ways to being a football quarterback. One of those ways is that when things go well the quarterback may get a little too much credit, and when things go not-so-well the quarterback may get too much blame. However, it is the quarterback who "calls the plays." With that in mind, a partial list of the accomplishments of the Intramural Program of the DCT while Bruce Chabner was "quarterback" includes the following: * The first human retroviruses, HTLV-1 and HTLV-2, were discovered and shown to be directly linked to the development of specific human malignancies. * Adoptive immunotherapy for human cancer was developed, offering exciting new additions to the anticancer armamentarium. * Paclitaxel (Taxol®) was developed, and shown to be the most important new anticancer agent in the past two decades. * The human genes responsible for the development of several specific malignancies were discovered, such as those for kidney cancer. * Development of blood tests to detect HIV-tainted blood. * Treatment strategies for pediatric AIDS were developed. * The AIDS Drug Development Program within the NIH was established. * New drugs for the treatment of AIDS and AIDS-related conditions were developed. * The only three drugs to date that have been specifically approved for the treatment of AIDS-AZT, DDI, and DDC-were developed under the guidance of the DCT, with Bruce Chabner as Scientific Director. * The first clinical trials conducted with each of these agents-AZT, DDI, and DDC-were performed in the Intramural Program of the DCT. * Concurrently, many of the exciting findings reported by the National Surgical Adjuvant Breast and Bowel Project over the past 10 years (as well as other cooperative groups) were a direct result of the strong support shown by Bruce Chabner during his tenure as Director of the Division of Cancer Treatment. Further, the list above does not include his personal labortory and clinical accomplishments, some of which are: * Development of the principles of use of important antimetabolites, such as methotrexate. * Elucidation of biochemical pathways affected, and the mechanisms of action, of antifols and other antimetabolites. * The conduct of seminal studies in the clinical staging of non-Hodgkin's lymphomas, using laparoscopy as a primary tool. * Important contributions to the development of multiagent regimens in the clinical treatment of lymphomas, and of Hodgkin's disease. * Developed and is editor of the textbook which is considered to be the primary reference source for anticancer chemotherapeutic agents [1]. With all of these accomplishments, his career is long from over. Having just become the Medical Director of the Cancer Center at the Massachusetts General Hospital, Bruce Chabner is uniquely poised to have an even more far-reaching impact on a discipline in which he has played such a strong seminal role. This author was never a postdoctoral fellow in Bruce Chabner's laboratory. However, more than any other single person, he has played a central role in my professional development. I know of many others for whom the same statement would be true. It is a pleasure for me to witness the launching of the second phase of an already tremendous career. From Advances in Cancer Treatment: The Chabner Symposium. Stem Cells 1996;14:64-65.
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PMID:Closing Remarks. 1038 2

A cancer study conducted by the National Cancer Institute's (NCI) AIDS/Cancer Study Group disputes claims that AZT and other nucleoside analogs can predispose people to non-Hodgkin's lymphoma (MHL). The study compared rates of NHL before and after AZT was widely prescribed for HIV infection. The data, which include large numbers of people with AIDS, do not support suggestions that non-Hodgkin's lymphoma risk is increased in people with AIDS taking AZT.
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PMID:AZT does not cause cancer. 1136 72

Musculoskeletal manifestations of the human immunodeficiency virus (HIV) are common and are sometimes the initial presentation of the disease. Knowledge of the conditions affecting muscle, bone, and joints in HIV-infected patients is essential for successful management. Myopathies may be caused by pyogenic infection (eg, pyomyositis), idiopathic inflammation (eg, polymyositis), or drug effect (eg, AZT myopathy). Characteristic skeletal infections, such as tuberculosis and bacillary angiomatosis, require a high index of suspicion for accurate diagnosis. Neoplastic processes, such as non-Hodgkin's lymphoma and Kaposi's sarcoma, occur more frequently as the immune system deteriorates. Inflammatory and reactive arthropathies are more prevalent in HIV-positive than HIV-negative individuals and include Reiter's syndrome, psoriatic arthritis, HIV-associated arthritis, painful articular syndrome, acute symmetric polyarthritis, and hypertrophic osteoarthropathy. Patients with atypical musculoskeletal complaints and a suspected history of exposure should be tested for HIV.
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PMID:Musculoskeletal manifestations of human immunodeficiency virus infection. 1237 82

Both the incidence and prevalence of human immunodeficiency virus infection are increasing in the world. Diseases of ENT districts are more frequent in human immunodeficiency virus-infected patients and involve all the otolaryngological sites. The otorhinolaryngological manifestations in association with HIV infection are mainly atypical, so common in the clinical practice, really aspecific and very frequent in ENT daily routine (such as sinusitis, otitis, etc.) and, therefore, immunodeficiency may not be suspected. In other cases, ENT evidence is more peculiar or unusual, such as opportunistic infections, rare neoplasm and tumours with an unusual course, giving a very high suspect of a human immunodeficiency virus-related infection. The most frequent malignant neoplasm is Kaposi's Sarcoma which is extremely rare in non-human immunodeficiency virus-infected subjects; the second most frequent is non-Hodgkin's lymphoma with 50% in extranodal sites (oral and maxillary sinus). Following a review of the literature, modifications caused by current antiretroviral treatment on head and neck manifestations of human immunodeficiency virus infection have been evaluated. Highly active antiretroviral therapy is a new therapeutic strategy, based on poly-chemo-therapeutic schemes, providing simultaneously two or more anti-retroviral drugs. We have used highly active antiretroviral therapy in human immunodeficiency virus infection since 1997, substituting previous mono-chemotherapy based on Zidovudine or Didanosine alone. Highly active antiretroviral therapy is extremely efficient in reducing the viral load of human immunodeficiency virus and increasing CD4+ T-lymphocyte count. These biological effects are associated with an improvement in immune functions. To evaluate the effects of highly active antiretroviral therapy on otorhinolaryngological manifestations in human immunodeficiency virus infection, we performed a retrospective study on 470 adults, observed over 14 years (1989-2002) and constantly receiving the same treatment, with follow-up from 7 to 80 months. A total of 250 subjects underwent mono-antiretroviral chemotherapy (1989-1996), while 220 underwent highly active antiretroviral therapy (1997-2002). The results of the retrospective study showed that highly active antiretroviral therapy has greatly improved the control of the immune-deficiency (increasing the range of CD4+), reducing the number of otorhinolaryngological manifestations (also tumours). On the other hand, 2 patients presented sudden unilateral hearing loss following treatment: toxicity due to association of new drugs cannot be excluded.
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PMID:Human immunodeficiency virus infection: personal experience in changes in head and neck manifestations due to recent antiretroviral therapies. 1608 Mar 13