Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The B-cell antigen CD20 is expressed on normal B cells and by nearly all B-cell lymphomas. This nonmodulating antigen provides an excellent target for antibody-directed therapies. A chimeric anti-CD20 antibody (IDEC-C2B8), consisting of human IgG1-kappa constant regions and variable regions from the murine monoclonal anti-CD20 antibody IDEC-2B8, has been produced for clinical trials. It lyses CD20+ cells in vitro via complement and antibody-dependent cell-mediated lysis. Preclinical studies have shown that the chimeric antibody selectively depletes B cells in blood and lymph nodes in macaque monkeys. In this phase I clinical trial, 15 patients (3 per dose level) with relapsed low-grade B-cell lymphoma were treated with a single dose (10, 50, 100, 250, or 500 mg/m2) of antibody administered intravenously. Treatment-related symptoms correlated with the number of circulating CD20 cells and grade II events consisted of fever (5 patients); nausea (2), rigor (2), orthostatic hypotension (2), bronchospasm (1), and thrombocytopenia (1). No significant toxicities were observed during the 3 months of follow-up. Serum C3, IgG, and IgM levels, neutrophils, and T cells were largely unchanged. At the three higher dose levels, pharmacokinetics of the free antibody showed a serum half-life of 4.4 days (range, 1.6 to 10.5). Levels greater than 10 micrograms/mL persisted in 6 of 9 patients for more than 14 days. No quantifiable immune responses to the infused antibody have been detected. CD20+ B cells were rapidly and specifically depleted in the peripheral blood at 24 to 72 hours and remained depleted for at least 2 to 3 months in most patients. Two-week postinfusion tumor biopsies showed the chimeric antibody bound to tumor cells and a decrease in the percentage of B cells. Tumor regressions occurred in 6 of 15 patients (2 partial and 4 minor responses). The results of this single-dose trial have been used to design a multiple-dose phase I/II study.
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PMID:Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. 752 29

Helicobacter pylori-like organisms (Hp) and polymorphonuclear leucocytes (PMNs) in 2614 gastroduodenal biopsies from 602 patients with dyspepsia, in Al Ain, United Arab Emirates, between October 1990 and October 1992, were histologically graded to determine the prevalence of Hp gastritis and their utilization in the evaluation of treatment efficacy in these patients. Symptoms of functional dyspepsia included, in order of frequency, abdominal pain or discomfort, flatulence, burning sensation, regurgitation, fullness, nausea, vomiting, bloating and belching. The biopsies were paraffin embedded, sectioned and stained with hematoxylin and eosin (H and E) to grade the inflammation. In addition to H and E, several special stains including modified Giemsa (MG), Wharthin-Starry silver and cold Ziehl-Neelsen stains were utilized to clearly identify Hp organisms. Giemsa method was found to be superior to other special stains in visualizing the Hp organisms in paraffin sections, and was utilized in every case. Two immunohistochemical markers for B cells (CD20) and T cells (CD45RO) were utilized for labeling lymphocytes infiltrating the lamina propria of the gastroduodenal biopsies in formalin-fixed paraffin-embedded sections. H and E and MG stained sections were utilized to count PMNs and Hp, and were graded 0, 1, 2, and 3, corresponding to none, mild, moderate, and severe grades of the Sydney system for classification of gastritis, respectively. Of the total initial 2318 endoscopic biopsies, 98.8% of the patients had suitable biopsies for histologic evaluation. Unsuitable biopsies were recovered from patients with gastric carcinoma. Inflammation was seen in 98.5% of 595 patients with suitable biopsies. In 74.5% of these patients the inflammation was active; 37.5, 32.5 and 4.5% had mild, moderate and severe active inflammation, respectively. In the remaining 24% of the 595 patients, the gastritis was chronic without activity or atrophic changes. As many as 73.6% of the patients with suitable biopsies were Hp positive; 39.8, 29.1 and 4.7% had grades 1, 2 and 3 Hp, respectively. Intestinal metaplasia was found in 28.9% of the 602 patients, and was seen more often in Hp positive than Hp negative patients (34.5 vs 14%, P < 0.005, for d.f. = 1; chi 2 = 10.35). Of the Hp positive patients, 172 and 46 patients attended the first and second follow-up endoscopy visits, respectively. The triple treatment was composed of one dose of tinidazole (2gm), doxycycline, 200 mg initial dose and 100 mg daily for two weeks, and bismuth subcitrate (Gist-Brocades nv, Delft, The Netherlands), 2 tablets twice daily for 4 weeks. After triple drug treatment, eradication of Hp was accomplished, histologically, in 38.4 and 45.7% of the patients on first and second follow-up visits, respectively. Thus, the Sydney system-based grading scale provides an objective histological evaluation of Hp gastritis for accurate prevalence studies, and may prove to be of value in estimating treatment efficacy.
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PMID:Grading Helicobacter pylori gastritis in dyspeptic patients. 881 77

The clinicopathological and immunohistochemical findings in 25 cases of inflammatory pseudotumor of lymph nodes (IPT) are presented. The patients were 13 women and 12 men between 8 and 81 years of age. Clinically, symptoms of prior infection, fatigue, abdominal pain, weight loss, fever of unknown origin, pelvic inflammatory disease, or nausea and night sweats were obtained in 15 patients, whereas six patients presented with asymptomatic lymphadenopathy. In four additional patients, no clinical information was obtained. The involved nodes included cervical, supraclavicular, inguinal, mesenteric, and mediastinal lymph nodes. In two cases, there was synchronous involvement of separate lymph node groups (inguinal and cervical in one case and cervical and mediastinal in another case), whereas in a third patient there was synchronous involvement of the spleen and a paraaortic lymph node. Histologically, the lesions were characterized by a fibrosing/inflammatory process that showed marked heterogeneity and striking variation from case to case. Based on their histological features, the lesions could be classified into three different groups: Stage I was characterized by the appearance of single or multiple small foci containing a spindle cell proliferation admixed with a prominent inflammatory background, with complete preservation of the remainder of the nodal architecture; stage II was characterized by more diffuse involvement of the lymph node with a marked inflammatory response admixed with a prominent myofibroblastic proliferation leading to subtotal effacement of the nodal architecture, often with extension of the process beyond the capsule into perinodal fat; and stage III was characterized by almost complete replacement of the lymph node by diffuse sclerosis with scant residual inflammatory elements and total loss of the normal nodal architecture. Immunohistochemical studies in 20 cases showed a striking number of vimentin- and actin-positive myofibroblastic cells with moderate increase in CD20/CD45+ small lymphocytes and polyclonal plasma cells in the stage I lesions, the emergence of numerous CD68+ histiocytes admixed with lymphocytes, plasma cells, and abundant fibromyofibroblastic cells in the stage II lesions, and only few remaining scattered CD68+ histiocytes and fibroblasts in the stage III lesions. Our findings suggest that inflammatory pseudotumor of lymph node represents an evolving, dynamic process that may adopt different morphological appearances depending on its stage of evolution. Recognition of the various stages of this process may be of importance for differential diagnosis with other fibrosing/inflammatory conditions of lymph nodes.
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PMID:Inflammatory pseudotumor of lymph nodes: a study of 25 cases with emphasis on morphological heterogeneity. 904 98

Cancer anorexia-cachexia syndrome (CACS), which is characterized by progressive weight loss (WL) and anorexia (A), is present in 50% of advanced cancer patients and in 80% of terminally ill cancer patients. One of the most controversial aspects of CACS is its oetiopathogenesis; experimental studies have identified certain cytokines [Tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), interleukin 6 (IL-6), and gamma interferon (gamma-IFN)] as possible co-factors in the onset of the syndrome. The aim of our study was to investigate the correlation between serum levels of circulating cytokines and severity of CACS. The following series of parameters was identified in 61 patients with advanced and terminal cancer: stage of disease; Karnofsky performance status (KPS) and clinical symptoms; biohumoral, anthropometric and immunological situation; level of circulating cytokines. All these parameters were evaluated for a possible link with WL/A. Our data do not show any significant correlation between circulating cytokines and WL/A. A direct correlation was identified between WL/A and nausea (P = 0.03 and P < 0.001, respectively) whereas inverse correlations were observed for both factors as regards arm circumference (P < 0.001 for both), wrist circumference (P < 0.001 for both), KPS (P < 0.001 and P = 0.003, respectively) and creatinine (P = 0.005 and P = 0.03, respectively). Other biochemical factors, such as haemoglobin, haematocrit, glycaemia, prealbumin, sodium and chlorine were also correlated with at least one of two clinical parameters in question. Unexpected results were seen in the increases in CD20 and CD4 and in the CD4/CD8 ratio. Serum levels of these cytokines do not, therefore, appear to be critical in the onset of CACS. On the contrary, our findings confirmed the clinico-laboratory picture that is characteristic of CACS. If we consider the possibility that CACS is provoked by an aspecific response of the host's defence mechanisms against prolonged neoplastic attack, the increase in CD4 (helper lymphocytes) could be linked to the persistent response.
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PMID:Serum levels of tumour necrosis factor alpha and other cytokines do not correlate with weight loss and anorexia in cancer patients. 932 57

Eleven patients with relapsed fludarabine-resistant B-cell chronic lymphocytic leukemia (CLL) or leukemic variants of low-grade B-cell non-Hodgkin's lymphoma (NHL) were treated with the chimeric monoclonal anti-CD20 antibody rituximab (IDEC-C2B8). Peripheral lymphocyte counts at baseline varied from 0.2 to 294.3 x 10(9)/L. During the first rituximab infusion, patients with lymphocyte counts exceeding 50.0 x 10(9)/L experienced a severe cytokine-release syndrome. Ninety minutes after onset of the infusion, serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) peaked in all patients. Elevated cytokine levels during treatment were associated with clinical symptoms, including fever, chills, nausea, vomiting, hypotension, and dyspnea. Lymphocyte and platelet counts dropped to 50% to 75% of baseline values within 12 hours after the onset of the infusion. Simultaneously, there was a 5-fold to 10-fold increase of liver enzymes, d-dimers, and lactate dehydrogenase (LDH), as well as a prolongation of the prothrombin time. Frequency and severity of first-dose adverse events were dependent on the number of circulating tumor cells at baseline: patients with lymphocyte counts greater than 50.0 x 10(9)/L experienced significantly more adverse events of National Cancer Institute (NCI) grade III/IV toxicity than patients with less than 50.0 x 10(9)/L peripheral tumor cells (P = .0017). Due to massive side effects in the first patient treated with 375 mg/m(2) in 1 day, a fractionated dosing schedule was used in all subsequent patients with application of 50 mg rituximab on day 1, 150 mg on day 2, and the rest of the 375 mg/m(2) dose on day 3. While the patient with the leukemic variant of the mantle-cell NHL achieved a complete remission (9 months+) after treatment with 4 x 375 mg/m(2) rituximab, efficacy in patients with relapsed fludarabine-resistant B-CLL was poor: 1 partial remission, 7 cases of stable disease, and 1 progressive disease were observed in 9 evaluable patients with CLL. On the basis of these data, different infusion schedules and/or combination regimens with chemotherapeutic drugs to reduce tumor burden before treatment with rituximab will have to be evaluated.
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PMID:Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). 1049 91

Lymphomas are the fifth most common malignancy in the United States and are increasing in incidence. Despite being among the most responsive malignancies to radiation and chemotherapy, the majority of patients relapse or have progressive disease. Monoclonal antibodies (MAbs) directed at cell-specific surface antigens have been useful in the diagnosis of lymphomas and, more recently, the therapeutic mouse-human chimeric MAb rituximab has demonstrated effectiveness in B cell lymphomas. Conjugating MAbs to radionuclides is a strategy for improving the efficacy of MAb lymphoma therapy by delivering radiation in close proximity to the tumour (radioimmunotherapy or RIT). In addition, the low dose rate of the delivered radiation may exert a greater antitumour activity than an equivalent dose of conventional external beam radiation. The antigenic targets for MAb therapy have included CD20, CD22, HLA-DR, and B cell idiotype. Radionuclides that have been used include iodine-131, yttrium-90, and copper-67; there are relative merits and disadvantages to each source of radiation. Clinical studies to date have focused on relapsed and refractory patients with both indolent and aggressive lymphomas, although more recent studies have included previously untreated patients with indolent lymphoma. Radioimmunoconjugate has been delivered as either single or multiple doses. Response rates have varied widely, dependent on the patient population and the response criteria. Of note, complete responses can be achieved in this typically refractory patient group. Toxicities have generally consisted of mild infusion-related nausea, fever, chills, and asthenia. Neutropenia and thrombocytopenia are the dose-limiting toxicities and have prompted the incorporation of autologous stem cell support as a means of achieving dose escalation. To date, RIT has been delivered to highly selected patients in relatively few centres with requisite equipment and specialised personnel. In addition to these requirements, cost is likely to be a barrier to widespread use. The combination of RIT with chemotherapy at conventional or high dose, or with biological agents is a fertile area for investigation. The potential of RIT in the treatment for lymphomas will be defined only by well designed comparative prospective clinical studies.
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PMID:Radioimmunotherapy: potential as a therapeutic strategy in non-Hodgkin's lymphoma. 1143 81

The treatment of primary central nervous system lymphoma (PCNSL) with chemo- and radiotherapy is efficient in terms of tumor response. However, time to tumor progression often is of short duration and leptomeningeal relapse is common. We present a 66-year-old man in third relapse of a CD20-positive PCNSL. After treatment with intravenous and intraventricular administration of the chimeric anti-CD20 monoclonal antibody rituximab, a total clearing of lymphoma cells in the cerebrospinal fluid (CSF) was achieved. There was no change in the size of the parenchymal tumor mass but there was slight improvement of clinical symptoms after therapy. Rituximab infusions (375 mg/m2) were first given systemically on days 1 and 8. Intraventricular injections of rituximab via Ommaya reservoir were given on days 16 (10 mg), 17 (40 mg), 24 (25 mg) and 25 (25 mg). Reversible side effects such as nausea, chills and hypotension were observed only immediately after intraventricular administration of 40 mg rituximab. Antibody levels in CSF were measured at 7 timepoints during and after the treatment period. These data suggest that intraventicular treatment with rituximab is safe and feasible with a potential activity on leptomeningeal tumor manifestation. Efficacy and pharmacokinetics of rituximab in PCNSL should be investigated in future trials.
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PMID:Intraventricular and intravenous treatment of a patient with refractory primary CNS lymphoma using rituximab. 1224 Nov 17

This phase 2 trial was performed to evaluate the safety and efficacy of the chimeric monoclonal anti-CD20 antibody rituximab in patients with relapsed lymphocyte-predominant Hodgkin lymphoma or other CD20(+) subtypes of Hodgkin disease (HD). Eligibility criteria required expression of the CD20 antigen on more than 30% of malignant cells. Fourteen patients were treated with 4 weekly intravenous infusions of rituximab (375 mg/m(2)). All patients had at least one prior chemotherapy (median, 2). The median time from first diagnosis was 9 years. Adverse events, such as rhinitis, fever, chills, and nausea, were usually transient and of mild to moderate grade, allowing outpatient treatment in most cases. All patients completed treatment and were eligible for a response. The overall response in 14 assessable patients was 86%, with 8 complete remissions and 4 partial remissions, and 2 patients with progressive disease. At a median follow-up of 12 months, 9 of 12 responders were in remission. The median duration of response has not been reached yet (20+ months). We conclude that rituximab is both safe and effective in a subgroup of CD20(+) patients with HD.
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PMID:Treatment of relapsed CD20+ Hodgkin lymphoma with the monoclonal antibody rituximab is effective and well tolerated: results of a phase 2 trial of the German Hodgkin Lymphoma Study Group. 1250 81

Most patients with non-Hodgkin's lymphoma (NHL) achieve remission but, despite newer drugs, the natural history of this disease has not improved during the last 20 years. Less than one half of patients with aggressive NHL are cured, and few of those with low-grade NHL are curable. Furthermore, NHL becomes progressively more chemoresistant while remaining responsive to external beam radiation therapy. Radioimmunotherapy (RIT) is a logical strategy for the treatment of NHL because this disease is multifocal and radiosensitive. Because of their remarkable effectiveness for RIT, 2 anti-CD20 monoclonal antibodies (mAbs), one labeled with (111)In for imaging or (90)Y for therapy and a second labeled with (131)I for imaging and therapy, have been approved for use in patients with NHL. These drugs have proven remarkably effective and safe. Evidence for the importance of the radionuclide is manifested by the data in the randomized pivotal phase III trial of (90)Y-ibritumomab that revealed response rates were several times greater in the (90)Y-ibritumomab arm than in the rituximab arm. A second drug for RIT, (131)I-tositumomab, was compared in a pivotal trial with the efficacy of the last chemotherapy received by each patient. Once again, response rates were much higher for RIT. Both (90)Y-ibritumomab and (131)I-tositumomab require preinfusion of several hundred milligrams of unlabeled anti-CD20 mAb to obtain "favorable" biodistribution, that is, targeting of NHL. Response rates for other mAbs and radionuclides in NHL also have been high but these drugs have not reached the approval stage. These drugs can be used safely by physicians who have suitable training and judgment. Unlike chemotherapy, RIT is not associated with mucositis, hair loss, or persistent nausea or vomiting. Although hematologic toxicity is dose limiting, hospitalization for febrile neutropenia is uncommon. Randomized trials of RIT in different formulations have not been conducted, but there is evidence to suggest that the mAb, antigen, radionuclide, chelator, linker, and dosing strategy may make a difference in the outcome.
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PMID:Treatment of non-Hodgkin's lymphoma (NHL) with radiolabeled antibodies (mAbs). 1609 94

A 59-year-old woman with goiter complained of nausea, vomiting and weight loss in April 2000. She underwent an endoscopic examination and was admitted to our hospital because gastric biopsy specimens revealed that she had diffuse large B-cell lymphoma. A thyroid biopsy also detected the diffuse infiltration of lymphoma cells, which were positive for CD19, CD20, CD38 and HLA-DR. Although the cells expressed surface immunoglobulin a chain, they lacked expressions of the kappa and lambda light chains. Chromosomal analysis of the thyroid cells showed 47, XX, t(2 ; 3)(q31 ; q13), + 3, t(8 ; 22)(q24 ; q11). After five courses of biweekly CHOP chemotherapy, she received autologous peripheral blood stem cell transplantation in October 2000. Currently, she has maintained complete remission for more than 4 years.
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PMID:[Diffuse large B-cell lymphoma expressing surface immunoglobulin heavy chain (Ig alpha) and lacking light chains]. 1644 Jul 40


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