Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 40-year-old male was admitted to the hospital with acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP). Two months before admission the patient had a high fever, general fatigue and mild epigastic tenderness. On admission, physical examination revealed numerous small tumors on the head, gingiva, neck, nasal ala, anterior forehead, anterior thoracic, bilateral sole and bilateral lower limbs. At that time, the CD4 cell count was 130/microliters. Upper GI endoscopy was performed because of sever epigastralgia and hematemesis. The gastric mucosa was diffusely nodular and erythematous with bleeding. This biopsy showed Kaposi's sarcoma, and the same findings were obtained from the duodenum, rectum and skin, AIDS with related cutaneous and gastrointestinal KS and PCP was diagnosed. We performed a combination of chemotherapy and Interferon-alpha therapy, and the KS almost completely disappeared within 3 months.
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PMID:[Efficiency of combination chemotherapy and interferon-alpha therapy in a patient with AIDS-related cutaneous and gastrointestinal Kaposi's sarcoma]. 874 13

Kaposi's sarcoma (KS) is a common malignancy in patients with acquired immunodeficiency syndrome (AIDS), classically appearing as red to purple plaques containing small papules and nodules. We report our experience with an adolescent orthotopic liver transplant recipient who presented with an unusual presentation of KS. The patient had a protracted multisystem illness that began with hemolytic anemia, fevers, and fatigue and progressed to pancreatitis, sinusitis, lymphadenopathy, and mouth ulcers. The diagnosis was made by a lymph node biopsy that was performed to evaluate for Epstein-Barr virus. The classical subcutaneous nodules characteristic of KS did not become evident until shortly before the patient died. We present this case to emphasize that KS in pediatric liver transplant patients can present as a multisystem disease that progresses to disseminated organ involvement before the characteristic subcutaneous manifestations are evident.
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PMID:Kaposi's sarcoma presenting as a protracted multisystem illness in an adolescent liver transplant recipient. 934 99

Two forms of recombinant interferon-alpha (IFN-alpha2a and IFN-alpha2b) have been approved by the Food and Drug Administration for a variety of clinical indications, including hairy cell leukemia, hepatitis, acquired immunodeficiency syndrome-related Kaposi's sarcoma, chronic myelogenous leukemia (IFN-alpha2a only), and adjuvant therapy for melanoma (IFN-alpha2b only), based on their proven clinical efficacy and acceptable safety profiles. The continued postmarketing monitoring of adverse reactions associated with IFN-alpha therapy has revealed some new toxicities. The most common adverse events associated with IFN-alpha therapy are flu-like symptoms, fatigue, anorexia, and central nervous system and psychiatric reactions. In particular, the incidence of depression has only recently been fully appreciated. Some of these side effects, particularly chronic fatigue, anorexia, and neuropsychiatric reactions, may become dose limiting. New approaches to minimize and manage the side effects of IFN-alpha therapy are needed.
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PMID:Safety profile of interferon-alpha therapy. 948 35

Three patients, negative for human immunodeficiency virus (HIV), with histologically and polymerase chain reaction-proven non-HIV Kaposi's sarcoma who received low-dose interferon (IFN) as first-line treatment because of disseminated symptomatic disease are reported. Applying 3-18 million IU of IFN-alpha 2a per day, 3 days a week, subcutaneously for 8-20 months, major responses were achieved in all three cases. Tumour regression was observed within 4 months and has continued for 57 and 18 months to date (cases 1 and 2, respectively). Influenza-like symptoms, including fever, headaches and fatigue, were mild side-effects. However, in the third patient interferon injections had to be stopped because of hepatic enzyme elevation. Including this case report, 27 non-HIV Kaposi's sarcoma patients subcutaneously treated with IFN-alpha have been reported in literature. Most therapy regimens included 3-18 million IU IFN-alpha per day for 3 days a week. Twenty of 27 patients, or 74%, responded to therapy, whereas seven patients or 26% had stable or progressive disease. Relapse after IFN withdrawal can occur but is frequently delayed and limited, as in case 1. Following the response to IFN treatment, human herpesvirus-8 DNA was detected in the blood mononuclear cells of all three patients, possibly contributing to future relapses.
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PMID:Non-human immunodeficiency virus Kaposi's sarcoma can be effectively treated with low-dose interferon-alpha despite the persistence of herpesvirus-8. 999 Mar 71

TNP-470, an analogue of fumagillin, has been shown to inhibit angiogenesis in vitro and in vivo. In 1992, TNP-470 entered clinical development for cancer as an anti-angiogenic agent. It is currently in Phase I/II trials in Kaposi's sarcoma, renal cell carcinoma, brain cancer, breast cancer, cervical cancer and prostate cancer. In early clinical reports, TNP-470 is tolerated up to 177 mg/m(2) with neurotoxic effects (fatigue, vertigo, ataxia, and loss of concentration) being the principal dose limiting toxicity (DLT). Terminal half-life values are short and have shown intermittent and intrapatient variation (range: 0.05 - 1.07 h). Recently, mechanistic studies have identified cell cycle mediators and the protein methionine aminopeptidase-2 (MetAP-2) as molecular targets of TNP-470 and fumagillin. Animal studies confirm some toxic effects on normal angiogenic processes such as the female reproductive system and wound healing, which will require caution and close monitoring in the clinic. TNP-470 is one of the first anti-angiogenic compounds to enter clinical trials, making it a valuable prototype for future trials of angiogenesis inhibitors in oncology.
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PMID:TNP-470: an angiogenesis inhibitor in clinical development for cancer. 1106 Jul 50

Human herpesvirus 8 (HHV-8) is a recently discovered gammaherpesvirus that is the etiologic agent of Kaposi sarcoma (KS). The natural history of primary HHV-8 infection, including clinical outcome and host immune responses that may be important in preventing disease related to HHV-8, has not been elucidated. The present study characterized the clinical, immunologic, and virologic parameters of primary HHV-8 infection in 5 cases detected during a 15-year longitudinal study of 108 human immunodeficiency virus type 1 seronegative men in the Multicenter AIDS Cohort Study. Primary HHV-8 infection was associated with mild, nonspecific signs and symptoms of diarrhea, fatigue, localized rash, and lymphadenopathy. There were no alterations in numbers of CD4(+) or CD8(+) T cells or CD8(+) T-cell interferon gamma (IFN-gamma) production to mitogen or nominal antigen. CD8(+) cytotoxic T-lymphocyte precursor (CTLp) and IFN-gamma reactivity were detected during primary HHV-8 infection, with broad specificity to 5 lytic cycle proteins of HHV-8 encoded by open reading frame 8 (ORF 8; glycoprotein B homolog of Epstein-Barr virus), ORF 22 (gH homolog), ORF 25 (major capsid protein homolog), ORF 26 (a minor capsid protein homolog), or ORF 57 (an early protein homolog), in association with increases in serum antibody titers and appearance of HHV-8 DNA in blood mononuclear cells. CD8(+) T-cell responses to HHV-8 decreased by 2 to 3 years after primary infection. This antiviral T-cell response may control initial HHV-8 infection and prevent development of disease.
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PMID:Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell response to viral lytic cycle proteins. 1129 May 99

Vestar has asked for a second time for Food and Drug Administration (FDA) approval of DaunoXome, a liposomal daunorubicin, for the treatment of patients with systemic Kaposi's Sarcoma (KS) based on results from a large phase III trial. Overall response rates were lower than expected in this trial, with only 23 percent responding to DaunoXome, and there were slightly more than expected cases of reported neutropenia. However, incidence of toxicity such as hair loss, fatigue, and neuropathy were significantly lower. One other liposomal anthracycline, Doxil, has also been recommended for approval. No trials as yet have been done to compare the two drugs' effectiveness, although quality-of-life issues make these drugs attractive candidates.
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PMID:Liposomal chemotherapies. 1136 53

HIV-positive patients are prone to many illnesses due to their weakened immune systems. Pneumocystis carinii pneumonia (PCP) and tuberculosis (TB) both cause respiratory difficulties, as well as fatigue, scratchy throat and weight loss. Cytomegalovirus (CMV) causes changes in vision. Cryptococcal meningitis and toxoplasmosis share symptoms of acute headaches, confusion and memory loss. Kaposi's Sarcoma (KS) causes red and purple skin legions to appear. Candidiasis symptoms reveal themselves in oral, esophagal and vaginal forms. Other AIDS-related diseases and symptoms are discussed.
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PMID:[Self-detection of symptoms]. 1136 15

Multicentric Castleman's disease (MCD) is a lymphoproliferative disorder that can be defined based upon both clinical and pathological characteristics. The clinical features of this frequently fatal disease include fever, generalized lymphadenopathy, fatigue, splenomegaly, hepatomegaly, and pancytopenia. Recently, severe forms of this disease have been diagnosed in HIV positive patients. Human herpesvirus type 8 (HHV-8) DNA sequences have been detected in peripheral blood mononuclear cells (PBMCs) of patients with Kaposi's sarcoma and MCD, regardless of HIV infection status. Treatment and outcomes in HIV associated MCD are generally unfavorable. We recently treated two HIV-positive patients diagnosed with aggressive MCD with daily oral etoposide (50 mg). The first patient had relapsed on several occasions despite previous therapy with doxil, paclitaxel, and oral ganciclovir. The second patient was treatment naive. Both patients had HHV-8 detectable by polymerase chain reaction in PBMCs, widespread tumor, and B-type symptoms when therapy was initiated. In both cases remissions (documented by computerized tomography) have been durable, 1.5 and 6 months, respectively, with minimal side effects. Oral etoposide may be a safe, tolerable, and active agent in MCD.
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PMID:Treatment of HIV-associated multicentric Castleman's disease with oral etoposide. 1142 Dec 97

In addition to immunomodulatory and cytokine-modulatory properties, thalidomide has antiangiogenic activity. It has been investigated in a number of cancers including multiple myeloma, myelodysplastic syndromes, gliomas, Kaposi's sarcoma, renal cell carcinoma, advanced breast cancer, and colon cancer. Its role has been best explored in myeloma, where, at daily doses of 100 to 800 mg, it is remarkably active, causing clinically meaningful responses in one-third of extensively pretreated patients and in over half of patients treated early in the course of the disease. It also acts synergistically with corticosteroids and chemotherapy in myeloma. Thalidomide produces improvement of cytopenias characteristic of myelodysplastic syndrome, resulting in the reduction or elimination of transfusion dependence in some patients. Responses have also been seen in one-third of patients with Kaposi's sarcoma, in a small proportion of patients with renal cell carcinoma and high grade glioma and, in combination with irinotecan, in some patients with colon cancer. Thalidomide is being investigated currently in a number of clinical trials for cancer. Drowsiness, constipation and fatigue are common adverse effects seen in 75% of patients. Symptoms of peripheral neuropathy and skin rash are seen in 30%. A minority of patients experience bradycardia and thrombotic phenomena. Despite the high frequency of adverse effects, those severe enough to necessitate cessation of therapy are seen in only 10 to 15% of patients. A therapeutic trial of thalidomide should be considered in all patients with myeloma who are unresponsive to or relapse after standard therapy. In other malignant diseases, the most appropriate way to use the drug is in the setting of well designed clinical trials. In the absence of access to such studies, thalidomide could be considered singly or in combination with standard therapy in patients with no meaningful therapeutic options.
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PMID:Thalidomide in cancer: potential uses and limitations. 1143 82


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