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)

The anti-CD25 immunotoxin (IT), RFT5-SMPT-dgA, was used in a phase I dose escalation trial in patients with refractory Hodgkin's lymphoma. The IT was constructed by linking the monoclonal antibody RFT5 via a sterically hindered disulfide linker to deglycosylated ricin-A. All patients in this trial were heavily pretreated with a mean of 5 (range, 2 to 8) different prior therapies, including autologous bone marrow transplantation in 8 of 15. The mean age was 29 years (range, 19 to 34 years). Thirteen of 15 patients had advanced disease (stage IV) with massive tumor burdens and 6 of 15 had B symptoms. The IT was administered intravenously over 4 hours on days 1, 3, 5, and 7 for total doses per cycle of 5, 10, 15, or 20 mg/m2. Patients received one to four cycles of treatment. The peak serum concentration of intact IT varied from 0.2 to 9.7 micrograms/mL. The serum half life (T1/2) of the IT ranged from 4.0 to 10.5 hours (mean, 6.1 hours). Side effects were related to vascular leak syndrome (VLS), ie, decreases in serum albumin, edema, weight gain, hypotension, tachycardia, myalgia, and weakness. Two patients had a National Cancer Institute (NCI) grade 2 allergic reaction with generalized urticaria and mild bronchospasm. At 15 mg/m2, 1 patient experienced a grade 3 myalgia. All 3 patients receiving 20 mg/m2 experienced NCI grade 3 toxicities (edema, nausea, dyspnea or tachycardia) and 1 patient had NCI grade 4 myalgia. Thus, the maximal tolerated dose was 15 mg/m2. Seven of 15 patients made human antiricin antibodies (> or = 1.0 microgram/mL) and 6 of 15 developed human antimouse antibodies (> or = 1.0 microgram/mL). Clinical response included 2 partial remissions, 1 minor response, 3 stable diseases, and 9 progressive diseases. As has been predicted from the preclinical tests, these data seem to indicate clinical efficacy of this new IT in heavily pretreated Hodgkin's patients, thus warranting further clinical investigation.
 ...
PMID:A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin's lymphoma. 900 41

This phase II trial was undertaken to determine the toxicities, response rate, pharmacokinetics and frequency of human anti-mouse antibody (HAMA) and anti-ricin antibody (HARA) when the B-cell restricted immunotoxin anti-B4-bR was administered to patients with previously treated multiple myeloma (MM). Five patients with MM were scheduled to receive a 7 d continuous infusion of anti-B4-bR. The initial four patients received therapy at 40 microg/kg lean body weight (LBW)/d. Two patients received a 7 d infusion, one patient received 6 d, and another patient 5 d of therapy. The fifth patient was treated for 7 d at a lower dose of 30 microg/kg LBW/d because of the side-effects observed in the initial patients. Pharmacokinetic studies demonstrated a peak serum level >2.6 nM in three of the patients. Side-effects of therapy included hepatic transaminase elevations, myalgias, thrombocytopenia, nausea, vomiting, decrease in performance status, and capillary leak syndrome. One patient developed HAMA and two patients HARA. One patient developed neurologic toxicity with akinetic mutism, and died following therapy. No patient demonstrated a significant decline in M-component during therapy. We concluded that anti-B4-bR can be administered by continuous infusion to patients with multiple myeloma, although immunotoxin levels >3 nM were associated with increased incidence of toxicity and required dose adjustment. Future trials using anti-B4-bR in MM will be needed to determine the optimal dose and administration schedule in this patient population, and to determine whether there is evidence of biologic activity.
 ...
PMID:Anti-B4-blocked ricin: a phase II trial of 7 day continuous infusion in patients with multiple myeloma. 969 66

This Phase II trial was undertaken to determine the safety, toxicity, and potential efficacy of the B-cell restricted immunotoxin anti-B4-blocked ricin (Anti-B4-bR) when administered as adjuvant therapy to patients in complete remission (CR) after autologous bone marrow transplantation (ABMT) for B-cell non-Hodgkin's lymphoma (NHL). Forty-nine patients with B-cell NHL in CR 46-202 days (median, 112 days) post-ABMT received Anti-B4-bR at a dose of 30 microg/kg lean body weight/day for 7 days by continuous i.v. infusion. Patients were eligible for up to two additional courses of therapy at 14-day intervals. A total of 83 courses of Anti-B4-bR were administered, with 31 patients receiving two or more courses of therapy. The mean serum level on day 7 of the first course was 0.77+/-0.41 nM. Reversible toxicities included hepatic transaminase elevations, thrombocytopenia, myalgias, fatigue, nausea, hypoalbuminemia, and dyspnea. Human antimouse antibody (HAMA) and/or human antiricin antibody (HARA) responses occurred in 23 patients at a median of 22 days from the initiation of Anti-B4-bR therapy (range, 11-100 days). The 4-year disease-free survival and overall survival are estimated at 56 and 72%, respectively. Twenty-six patients remain in CR after a median follow-up of 54.5 months. This study demonstrates that Anti-B4-bR can be administered safely to patients as adjuvant therapy early after ABMT for B-cell NHL. The toxicities are tolerable and reversible. Although the early estimate of disease-free survival was very encouraging in this single-armed trial, the 4-year follow-up data demonstrate continued relapse.
 ...
PMID:A Phase II study of adjuvant therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with relapsed B-cell non-Hodgkin's lymphoma. 1049 9

The castor bean plant (Ricinus communis L.) or wonder tree is cultivated in many countries as an ornamental annual plant in gardens. The highest concentration of the lectin ricin is present in the seeds and pods. Ricin is considered as one of the most toxic natural poisons. Ricinine is a piperidine alkaloidal toxin present in castor bean and is described as a biomarker for the exposure to ricin. A case report is presented of a 49-year-old man who committed suicide by intravenous and subcutaneous injection of a castor bean extract. He was brought to the emergency department 24 h after injecting himself. On admission, the patient was conscious and he presented with a history of nausea, vomiting, diarrhoea, dyspnoea, vertigo and muscular pain. Despite symptomatic and supportive intensive care, the man died 9 h after admission due to multiorgan failure. A body external examination was performed. Blood, urine, vitreous humour and the castor bean extract were submitted to the laboratory for toxicological analysis. The identification of ricinine in the extract was performed by solid phase extraction in combination with full-scan gas chromatography/mass spectrometry, high-performance liquid chromatography with photodiode array detection and liquid chromatography/mass spectrometry operated in the full-scan mode, respectively. An extraction procedure with Oasis HLB solid phase extraction cartridges was applied. Chromatography was achieved using a Symmetry C18 column using a gradient mode with 0.15% formic acid and 0.15% formic acid in acetonitrile as mobile phase. Exposure to the castor bean extract was confirmed by identification of the biomarker ricinine in blood, urine and vitreous humour using solid phase extraction and liquid chromatography tandem mass spectrometry with electro spray source in positive ionization mode. Multiple reaction monitoring was used for specific detection. To the authors' knowledge, it is the first time that ricinine has been identified in vitreous humour in a case of castor bean poisoning. Based on the clinical symptoms and the results of the toxicological analysis, we concluded that death was caused by intoxication with plant toxins originated from R. communis L.
 ...
PMID:Suicidal death after injection of a castor bean extract (Ricinus communis L.). 1947 90

Since the late 70s of the last century there were more than 700 incidents related to the use of the ricin toxin. For this reason, CDC (Center of Disease Control and Prevention) recognized toxin as a biological weapon category B. The lethal dose of ricin toxin after parenteral administration is 0.0001 mg/kg and after oral administration 0.2 mg. The first symptoms of poisoning occur within a few hours after application of toxin as a nausea, vomiting and abdominal pain. In the final stage there are observed: cardiac arrhythmia, collapse and symptoms suggestive of involvement of the central nervous system. Stage immediately preceding death is a state of coma. The ricin toxin is still the substance against which action has no optimal antidote. Developed a vaccine called RiVax is waiting for its registration. It should be pointed out that the availability of a ricin toxin makes it possible to use it for real bioterrorists.
...
PMID:[Today's threat of ricin toxin]. 2644 79

Ricin is a highly toxic agent derived from the castor bean plant (Ricinus communis). Poisoning occurs commonly by oral ingestion of the beans. Injection of ricin is believed to be more lethal. Ricin is a large glycosylated protein difficult to detect in clinical samples. Instead, ricinine, a small alkaloid found in the same beans, is used as surrogate marker for ricin exposure. We describe a simple LC-MS/MS method for the detection of ricinine in serum, blood and urine, validated according to EMA guidelines and successfully applied to patient samples of a suicidal death after injection of a castor bean extract. A 26-year-old man self-presented to the emergency department with severe abdominal cramps and nausea after injection of a castor bean extract. Due to rapid deterioration of his hemodynamic function despite early aggressive fluid resuscitation, he was transferred to ICU. Abdominal cramps worsened and a fulminant diarrhea developed, resulting in hypovolemic shock and cardiorespiratory collapse. Despite full supportive therapy, the patient died approximately 10 hours after injection due to multiple organ failure. Ricinine was quantified by LC-MS/MS after LLE with diethyl ether using ricinine-D3 as internal standard. Six hours after injection, ricinine concentrations in serum and blood were 16.5 and 12.9 ng/mL, respectively, which decreased to 12.4 and 10.6 ng/mL, 4 hours later. The urinary concentration was 81.1 ng/mL 7 hours after injection, which amply exceeded the levels previously reported in similar cases with lethal outcome. Concentrations of ricinine, compatible with a lethal exposure to castor beans, were detected in serum, blood and urine. Ricinine was also found in bile and liver tissue.
 ...
PMID:Lethal Injection of a Castor Bean Extract: Ricinine Quantification as a Marker for Ricin Exposure Using a Validated LC-MS/MS Method. 3059 May 81