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

We report on a 56-year-old woman with acute lymphocytic leukemia who presented with right upper quadrant pain, fever, nausea, and vomiting. Laboratory studies confirmed fungemia with Trichosporum beigelii, and contrast-enhanced computed tomography of the abdomen demonstrated numerous low-attenuation liver lesions and a hypodense spleen with capsular enhancement suggestive of complete splenic infarction. Subsequent splenectomy confirmed that the spleen was completely infarcted and infiltrated with Trichosporum. The patient had a difficult postoperative course and died despite aggressive antifungal therapy.
 ...
PMID:Fatal, complete splenic infarction and hepatic infection due to disseminated Trichosporon beigelii infection: CT findings. 1529 Sep 51

Clofarabine (2-chloro-2'-fluoro-deoxy-9-beta-D-arabinofuranosyladenine) is a second-generation nucleoside analog with activity in acute leukemias. As clofarabine is a potent inhibitor of ribonucleotide reductase (RnR), we hypothesized that clofarabine will modulate ara-c triphosphate accumulation and increase the antileukemic activity of cytarabine (ara-C). We conducted a phase 1-2 study of clofarabine plus ara-C in 32 patients with relapsed acute leukemia (25 acute myeloid leukemia [AML], 2 acute lymphoblastic leukemia [ALL]), 4 high-risk myelodysplastic syndrome (MDS), and 1 blast-phase chronic myeloid leukemia (CML).(1) Clofarabine was given as a 1-hour intravenous infusion for 5 days (days 2 through 6) followed 4 hours later by ara-C at 1 g/m(2) per day as a 2-hour intravenous infusion for 5 days (days 1 through 5). The phase 2 dose of clofarabine was 40 mg/m(2) per day for 5 days. Among all patients, 7 (22%) achieved complete remission (CR), and 5 (16%) achieved CR with incomplete platelet recovery (CRp), for an overall response rate of 38%. No responses occurred in 3 patients with ALL and CML. One patient (3%) died during induction. Adverse events were mainly less than or equal to grade 2, including transient liver test abnormalities, nausea/vomiting, diarrhea, skin rashes, mucositis, and palmoplantar erythrodysesthesias. Plasma clofarabine levels generated clofarabine triphosphate accumulation, which resulted in an increase in ara-CTP in the leukemic blasts. The combination of clofarabine with ara-C is safe and active. Cellular pharmacology data support the biochemical modulation strategy.
 ...
PMID:Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. 1548 72

Clofarabine is a purine nucleoside analog that inhibits DNA synthesis and repair. Its effects are mediated via the inhibition of ribonucleotide reductase and DNA polymerase. Clofarabine also disrupts the integrity of mitochondrial membranes, resulting in programmed cell death. In 61 pediatric patients with relapsed or refractory acute lymphoblastic leukemia treated with clofarabine 52 mg/m2 infused intravenously over 2 hours once daily for 5 days every 2-6 weeks, rates of complete remission, complete remission without platelet recovery, and partial remission were 12%, 8%, and 10%, respectively. Data are from two non-comparative, multicenter, phase II studies. The most common adverse events associated with clofarabine 52 mg/m2 once daily for 5 days every 2-6 weeks in 96 patients with acute myelogenous or lymphoblastic leukemia (combined analysis of phase I/II trials) were hematologic events (including anemia, leukopenia, thrombocytopenia, neutropenia, and febrile neutro-penia), gastrointestinal events (including vomiting, nausea, and diarrhea), infections, and transient elevations in liver enzymes. Capillary leak syndrome or systemic inflammatory response syndrome was reported in four patients.
 ...
PMID:Clofarabine: in pediatric patients with acute lymphoblastic leukemia. 1611 62

The purpose of the study was to identify the association between chemotherapy-induced nausea/vomiting and changes to the electrogastrogram (EGG) of two children suffering from leukemia. After receiving written consent/assent, the children, both with acute lymphoblastic leukemia (ALL), were recruited. One of the subjects, a ten year-old boy, was given 1.1 gm Cytarabine (intravenous infusion for six hours per day) for three days and Tropisetron 5 mg intravenous infusion for 24 hours. The other subject, an eight year-old girl, received the induction phase of TPOG 93HR chemotherapy, which included Epirubicin, Vincristin, L-asparaginase, and Prednisolone and Tropisetron 5 mg on Day 1. The EGG recordings of both patients were recorded for a total of 42 hours by cutaneous electrogastrography over a seven day period. This included two-hour and four-hour readings taken before and immediately following the administration of chemotherapy each day. The position, movements, and activities of the children while on the EGG were recorded on digital video. Four episodes of nausea and vomiting were detected during this period. Pre- and post-nausea and vomiting during the EGG were analyzed using spectrum analysis after the deletion of motion artifacts. The findings of this study indicated that two episodes of nausea were 5.3-10.3% bradygastria and 2.1-10.3% tachygastria, with 85.8% and 100% normal gastric slow waves detected by EGG during the pre-vomiting period. Tachygastria was present in 3.4% and 12.2% of the post-vomiting period of each episode. The association of artifacts with position, movement, and activities must be considered during data collection.
 ...
PMID:[A pilot study: gastric motility and nausea/vomiting in two leukemia children receiving chemotherapy]. 1647 72

We evaluated efficacy and toxicity profiles of fludarabine, Ara-C, idarubicin, and G-CSF (Ida-FLAG) combination chemotherapy in 56 refractory and/or relapsed acute leukemia patients. Patients were treated with fludarabine phosphate 25 mg/m2/d (d1-5), Ara-C 2 g/m2/d (d1-5), idarubicin 12 mg/m2/d (d1-3), G-CSF was given subcutaneously from sixth day until absolute neutrophil count (ANC) >500/microL. One third of the acute myeloblastic leukemia (AML) and 45% of acute lymphoblastic leukemia (ALL) cases were primary refractory disease. In AML patients, complete remission (CR) was achieved in 15 cases (53.6%). One case showed partial remission (PR) (3.6%) and 12 cases (42.8%) had resistant to this regimen (RD). Grade IV hematologic toxicity occurred in all AML cases. Leukocyte recovery time was 16 days. Nonhematologic complications were mild to moderate nausea, vomiting, and mucositis and could be controlled by routine measures. Stem cell transplantation was performed in 5 patients and all achieved CR, 2 autologous and 3 allogeneic. In ALL patients, CR and PR were obtained in 8 (42.2%) and 2 (10.5%) of 22 cases; disease was resistant to Ida-FLAG in 9 (47.3%) cases. Grade IV hematologic toxicity occurred in all ALL cases. Leukocyte recovery time was 17 days. Nonhematologic toxicity consisted of nausea, vomiting, and mucositis and could be controlled by supportive therapy. Autologous transplantation was performed in 1 patient, but relapse disease occurred after 5 weeks. There was no correlation between response rate and leukemia subtype (AML versus ALL), leukocyte count, age, sex, disease status (de novo versus secondary), and RFS (early versus late relapse) (P > 0.05). Median survival was 16 weeks in all cases (22 weeks in AML versus 13 weeks). At present, only 3 patients are alive and 2 of these are in continuous remission. The rest of the patients died. In conclusion, Ida-FLAG is a good choice in cases with refractory/relapsing acute leukemia for salvage chemotherapy. High efficacy and a low-toxicity profile are preferable properties of this regimen, and this regimen has been found to be useful for cytoreduction, especially in candidates for allo-SCT.
 ...
PMID:IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience. 1698 32

Relapse occurs frequently after allogeneic hematopoietic cell transplantation (HCT) for treatment of high-risk Philadelphia chromosome-positive (Ph+) leukemia. Administration of imatinib early after HCT might provide an effective approach for preventing recurrent Ph+ leukemia, but the feasibility of this approach has not been systematically tested. Twenty-two patients, 15 with Ph+ acute lymphoblastic leukemia and 7 with high-risk chronic myelogenous leukemia, were enrolled in a prospective study and given imatinib from the time of engraftment until 365 days after HCT. Before day 90, adults (n = 19) tolerated a median average daily imatinib dose of 400 mg/d (range, 200-500 mg/d), and children (n = 3) tolerated 265 mg/m2/d (range, 200-290 mg/m2/ d). The most common adverse events related to imatinib administration were grade 1-3 nausea, emesis, and serum transaminase elevations. We conclude that imatinib can be safely administered early after myeloablative allogeneic HCT at a dose intensity comparable to that used in primary therapy.
 ...
PMID:Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. 1711 11

Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase inhibitor active clinically in cutaneous T-cell lymphoma and preclinically in leukemia. A phase 1 study was conducted to evaluate the safety and activity of oral vorinostat 100 to 300 mg twice or thrice daily for 14 days followed by 1-week rest. Patients with relapsed or refractory leukemias or myelodysplastic syndromes (MDS) and untreated patients who were not candidates for chemotherapy were eligible. Of 41 patients, 31 had acute myeloid leukemia (AML), 4 chronic lymphocytic leukemia, 3 MDS, 2 acute lymphoblastic leukemia, and 1 chronic myelocytic leukemia. The maximum tolerated dose (MTD) was 200 mg twice daily or 250 mg thrice daily. Dose-limiting toxicities were fatigue, nausea, vomiting, and diarrhea. Common drug-related adverse experiences were diarrhea, nausea, fatigue, and anorexia and were mild/moderate in severity. Grade 3/4 drug-related adverse experiences included fatigue (27%), thrombocytopenia (12%), and diarrhea (10%). There were no drug-related deaths; 7 patients had hematologic improvement response, including 2 complete responses and 2 complete responses with incomplete blood count recovery (all with AML treated at/below MTD). Increased histone acetylation was observed at all doses. Antioxidant gene expression may confer vorinostat resistance. Further evaluation of vorinostat in AML/MDS is warranted.
 ...
PMID:Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes. 1796 10

At concentrations >0.1 mM, hydroxyurea (HU) enhances the accumulation of cytosine arabinoside (ara-C) in leukemia cells in vitro. This study of children with refractory acute leukemia was designed to take advantage of this biochemical modulation. A fixed dose of HU and an escalating dose of ara-C were used. Oral HU (1200 mg/m2) was followed 2 hours later by ara-C (250-3100 mg/m2) intravenously in 15 minutes. The combination was given on days 1, 2, 3 and 8, 9, 10. Thirty-three children [26 acute lymphocytic leukemia (ALL), 7 acute nonlymphocytic leukemia] were treated; 29 received at least 1 full course. All patients developed grade 4 cytopenias. Other grade 3 to 4 toxicities included hyperbilirubinemia (2), elevated transaminases (3), transient gait disturbance (1), stomatitis (3), typhlitis (1), nausea/vomiting (9), and marrow aplasia >4 weeks (1). Three patients had intracranial bleeds while thrombocytopenic. Only liver toxicities and nausea/vomiting exhibited any dosage effect. The maximum tolerated dose of ara-C was 2400 mg/m2. There were 6 complete responses (5 ALL), 5 partial responses (3 ALL), and 19 patients with no response or progressive disease. There was no dosage effect for response with 2 complete responses occurring at the lowest ara-C level. Responses were transient (1 to 3 mo). Twenty of twenty-six patients achieved a peak serum HU level >0.5 mM by 2 hours after the HU dose. The mean level at 2 hours was 0.57 mM (range: 0.21 to 0.99 mM). This combination of HU and ara-C is tolerable and has efficacy in refractory leukemias. Responses at the lowest ara-C dose level suggests synergism.
 ...
PMID:Sequential oral hydroxyurea and intravenous cytosine arabinoside in refractory childhood acute leukemia: a pediatric oncology group phase 1 study. 1845 68

Solar burn reactivation, a rare and idiosyncratic drug reaction, has been reported with the use of a variety of drugs. This reaction is believed to be the result of exposure to ultraviolet light during the subsiding phase of an acute inflammatory reaction. It affects areas of the body that have been previously sunburned. We describe a 16-year-old girl who was receiving treatment for acute lymphoblastic leukemia and experienced a second-degree solar burn reactivation reaction to methotrexate. The patient had a mild sunburn on her face and shoulders the day she went to the oncology clinic for her interim maintenance chemotherapy with vincristine 1.5 mg/m(2)/dose and methotrexate 100 mg/m(2)/dose. Three days later, she returned to the clinic with a 2-day history of fever (<or= 100.2 degrees F), nausea, vomiting, and malaise; the sunburn on her face and shoulders also had become severe, without further sun exposure. Laboratory results revealed elevated blood urea nitrogen and serum creatinine concentrations, and her methotrexate level was elevated at 0.9 mM. The patient was diagnosed with acute renal failure, dehydration, methotrexate toxicity, and second-degree solar burn reactivation reaction. She was admitted to the children's hospital and treated with sodium bicarbonate, acetaminophen with codeine, ondansetron, and silvadene cream. On hospital day 3, the patient's methotrexate level decreased to less than 0.1 mM. The sunburn continued to heal, and after a 14-day hospital stay, complicated by a streptococcal infection, grade 3 mucositis, bacteremia, and mild gastritis and duodenitis, the patient recovered and was discharged. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patient's solar burn reactivation and methotrexate. Although methotrexate-induced solar burn reactivation is rare, clinicians should be aware of this potential adverse reaction and consider delaying administration of methotrexate by 5-7 days if a patient reports ultraviolet-related erythema in the past 2-4 days or presents with a notable sunburn.
 ...
PMID:Solar burn reactivation induced by methotrexate. 2033 62

Although allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL), the prognosis of patients who relapse after allogeneic HSCT has been extremely poor. Dasatinib, a second-generation tyrosine kinase inhibitor, is a promising agent for the treatment of Ph-ALL. We report on a Ph-ALL patient who relapsed early after the first allogeneic HSCT, but achieved complete molecular remission with dasatinib alone. She remains in molecular remission 12 months after the second allogeneic HSCT. Dasatinib was generally well tolerated, but she developed myalgia, nausea and positive cytomegalovirus antigenemia. In addition, sudden-onset bloody diarrhea was observed 10 days after the second HSCT, which was possibly associated with the use of dasatinib in addition to the effect of the conditioning regimen and graft-versus-host disease. In conclusion, dasatinib is an effective agent for Ph-ALL with a poor prognosis, but may be associated with specific adverse events including opportunistic infection and gastrointestinal bleeding.
 ...
PMID:Dasatinib followed by second allogeneic hematopoietic stem cell transplantation for relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia after the first transplantation. 2082 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>