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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excessive fluid and electrolyte secretion, resulting symptomatically in diarrhea, has been associated with mast cell activation in a variety of experimental and clinical settings. The present study has used a human colonic epithelial cell line to examine mechanisms underlying this phenomenon. Acute addition of mixed mast cell mediators (as a lysate of rat basophilic leukemia cells) to epithelial cells led to prompt and sustained chloride secretion. The response was partially inhibitable by an antihistaminic drug and an adenosine antagonist, suggesting that histamine, adenosine, and possibly other mediators are responsible for producing the acute effect. Supernatants from immunologically activated rat basophilic leukemia cells had similar effects. Chronic exposure of epithelial cells to the lysate mediator preparation, followed by washing, had no effect on their basal electrical or electrolyte-transporting properties. However, the chloride secretory response of the cells to subsequent addition of vasoactive intestinal peptide, carbachol, and heat-stable enterotoxin of Escherichia coli was significantly enhanced, whereas responses to an adenosine agonist or PGE1 were unaffected. This study has, therefore, demonstrated two ways in which mast cell mediators can directly influence intestinal epithelial cells to secrete more chloride and, hence, to enhance fluid secretion in the gut. The findings may be of relevance to our understanding of inflammatory diarrhea and may aid the development of novel therapies for this disorder.
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PMID:Immune-related intestinal chloride secretion. III. Acute and chronic effects of mast cell mediators on chloride secretion by a human colonic epithelial cell line. 165 Mar 88

In a 72-year-old man with watery diarrhoea and leukocytosis the proliferation of abnormal cells was studied in specimens obtained by endoscopic biopsy of the gastrointestinal tract. Flow cytometry of leukaemia cells revealed a monoclonal expansion of "double-negative" (CD4-, CD8-) cells bearing T-cell receptor (TCR) alpha beta products. Southern blotting confirmed monoclonal integration of HTLV-I. A novel T-cell subset of double-negative TCR alpha beta cells in the gastrointestinal tract in adult man may be a target for HTLV-I infection.
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PMID:Leukaemia of novel gastrointestinal T-lymphocyte population infected with HTLV-I. 167 10

Beyond infancy, pneumatosis cystoides intestinalis (PCI) is rare. Data concerning pathogenesis and treatment are limited. Our experience with 12 children was examined to define predisposing factors, presentation, treatment, and outcome. Nine children were immunosuppressed, thus identifying an important etiologic subgroup. Presentation was variable but included abdominal pain, distention, diarrhea and hematochezia. Clostridium difficile was found in 3 patients and cytomegalovirus in 1. Radiographs showed free air in 3. Nine were treated with antibiotics and bowel rest, 1 with bowel rest alone, 1 with oral metronidazole, and 1 with observation. PCI resolved in 7 of 9 treated with antibiotics, although 1 child with leukemia had severe hematochezia secondary to colonic ulceration and required hemicolectomy. No other patient required laparotomy. The free air resolved in 2 of 3. There were 2 deaths, both from sepsis. One had free air on admission but no perforation was found at autopsy. Treatment recommendations remain unclear; however, C difficile and cytomegalovirus are important pathogens that should be identified and treated promptly. In symptomatic patients, bowel rest and antibiotics seem beneficial. Operative intervention should be reserved for patients with peritoneal signs, progressive deterioration, obstruction, or persistent, severe bleeding. Free air alone is not an indication for operative management in children with PCI.
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PMID:Pneumatosis cystoides intestinalis in children beyond the first year of life: manifestations and management. 176 11

Because of the synergy seen in adult trials when 5-fluorouracil is combined with leucovorin, we initiated a Phase I trial of this combination in children's refractory cancer. Leucovorin, an equal mixture of the (6R,S)-diastereoisomers, was administered p.o. for 6 consecutive days as 4 equal doses at 0, 1, 2, and 3 h totaling 500 mg/m2/day. 5-Fluorouracil was given daily on days 2 to 6 as an i.v. bolus immediately following the last dose of leucovorin. The leucovorin dose was held constant while the 5-fluorouracil dose was escalated in cohorts of patients from 300 mg/m2/day to its maximally tolerated dose. Thirty-five patients (19 with acute leukemia and 16 with solid tumors) were evaluable for toxicity. The maximally tolerated dose of FUra was 450 mg/m2/day for 5 treatments for patients with solid tumors and 650 mg/m2/day for 5 treatments for the children with leukemia. The dose-limiting toxicities were myelosuppression and stomatitis. Other side effects included transient, mild elevations of serum transaminases, mild nausea, vomiting, and diarrhea. The pharmacokinetics of high-dose p.o. leucovorin was studied in 23 children. There was considerable interpatient variability in the plasma concentrations of total bioactive folates (TBAF), (6S)-leucovorin, and (6S)-5-methyltetrahydrofolic acid. The maximum plasma concentration (Cmax) of TBAF was 821 +/- 97 (SE) nM, occurring at a median of 8 h; the Cmax of (6S)-leucovorin was 77 +/- 11 nM, occurring at 4 h. The TBAF concentration fell to 146 +/- 42 nM by 24 h. (6S)-5-Methyltetrahydrofolic acid accounted for 90 +/- 7% of the TBAF at the Cmax. The plasma concentration of (6R)-leucovorin, the unnatural isomer, was equal to that of TBAF. Thus, p.o. leucovorin reduced the 5-fold excess of (6R)-leucovorin over TBAF seen after i.v. doses. The relative amounts of the three major plasma species were approximately the same as in adults, even though the Cmax of each compound was lower.
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PMID:Pharmacology and phase I trial of high-dose oral leucovorin plus 5-fluorouracil in children with refractory cancer: a report from the Children's Cancer Study Group. 189 77

Thirty two patients with refractory or recurrent acute leukemia or blast crisis of chronic myelocytic leukemia were treated with 1-beta-D-arabinofuranosylcytosine (Ara-C), 100 mg/m2 [group I (n = 15)] or 200 mg/m2 [group II (n = 18)], and tetrahydrouridine (THU) 350 mg/m2, given concurrently as a 3 h continuous intravenous infusion at 12 h interval for eight doses. Two of 13 (15.3%) evaluable patients in group I achieved a complete response, both of whom had acute myelocytic leukemia. In group II, seven of 14 evaluable patients (50%) obtained objective responses--six with complete responses (42.8%) and one with partial response (7%). Myelosuppression was seen in all patients with a median duration of 32.5 days (group I) and 36.3 days (group II), respectively. Non-hematologic toxicity consisted of nausea, vomiting, diarrhea, conjunctivitis, skin rash, hepatocellular toxicity, hemorrhage, and renal toxicity. Pharmacokinetic studies revealed, for group I, mean peak plasma Ara-C levels at 3 h (Cp3h) of 1254 ng/ml, area under the curve (AUC) 4651 ng x h/ml, total body clearance (TBC) 32.65 l/h/m2, renal clearance (RC) 7.04 l/h/m2 with a mean of 12.36% of the injected amount of Ara-C excreted unchanged in urine over the first 24 h. The corresponding mean values for group II are Cp3h 3305 ng/ml, AUC 15080 ng x h/ml, TBC 20.48 l/h/m2, RC 7.02 l/h/m2 and 26.23%. Ara-C 200 mg/m2 combined with THU gave serum Ara-C levels and response rates comparable to those achieved with high dose Ara-C (HiDAC) (greater than or equal to 1 g/m2). Central nervous system toxicity associated with HiDAC was not seen. Pharmacokinetics for uracil arabinoside (Ara-U) in patients treated with Ara-C 200 mg/m2 plus THU, were comparable to values seen with Ara-C for Cp3h, AUC and 24 h urine, amounting to 3160 ng/ml, 21717 ng x h/ml and 23.62% whereas TBC was significantly lower (p less than 0.001) for Ara-U than for Ara-C (3.02 versus 20.48 l/h/m2).
Leukemia 1991 Nov
PMID:Therapy of refractory/relapsed acute leukemia with cytosine arabinoside plus tetrahydrouridine (an inhibitor of cytidine deaminase)--a pilot study. 196 Oct 42

Biotechnological methods offer promising approaches for improved diagnostic and prophylactic purposes. The following biotechnological techniques are used in the Institute of Virology at the Hanover Veterinary School:--Production of monoclonal antibodies directed against viral and bacteria-specific antigens such as bovine virus diarrhoea virus, classical swine fever (hog cholera) virus, feline leukaemia virus, animal parvoviruses, Alphavirus, Brucella and Francisella--Establishment of improved and sensitive diagnostic enzyme immunoassays (ELISA) using monoclonal antibodies--Molecular cloning and sequencing of classical swine fever virus RNA and parvovirus DNA--Development of diagnostic hybridisation techniques (dot, slot, Southern and Northern blot, in situ, oligonucleotides)--Detection of viral genomes in tissues of infected animals--Development of synthetic oligopeptides as diagnostic antigens and as potential immunogens for vaccines. Currently available techniques used in basic research (e.g. pathogenesis studies) will be tested for their application in routine diagnosis of viral diseases, e.g. by molecular hybridisation. Some techniques need to be simplified (e.g. RNA extraction procedures) and, particularly, alternative labelling schedules must be developed (e.g. biotin or sulfone labelling instead of radionuclides).
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PMID:Use of biotechnical methods in veterinary medicine. 196 25

Thirteen patients with leukemia were treated with a combination of cytosine arabinoside (ara-C) (3 g/m2 by 1-h infusion every 12 h for 12 doses) and etoposide (100 mg/m2 daily over 1 h for 3 doses). Toxicity of the regimen consisted of severe hematologic suppression, moderate abdominal colic with vomiting and diarrhea, and occasionally severe central nervous system (CNS) toxicity. Two patients received the regimen as consolidation for acute myelogenous leukemia in remission. Of the remaining 11 patients with chronic myeloid leukemia (CML)-blast crises or relapsed/refractory acute myeloid leukemia (AML), nine patients (82%) obtained CR (or chronic phase) and two patients obtained partial remission (PR). High-dose ara-C and etoposide is an effective but toxic regiment for the treatment of relapsed or refractory myeloid leukemias.
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PMID:High-dose cytosine arabinoside and etoposide in the treatment of relapsed or refractory adult leukemia. 198 40

Preexistent feline leukemia virus (FeLV) infection greatly potentiated the severity of the transient primary and chronic secondary stages of feline immunodeficiency virus (FIV) infection. Of 10 FeLV-FIV carrier cats, 5 died of experimentally induced FIV infection, compared with 2 deaths in 10 cats infected only with FeLV and 1 death in 7 cats infected only with FIV. FIV-infected cats with preexistent FeLV infections developed severe depression, anorexia, fever, diarrhea, dehydration, weight loss, and leukopenia 4 to 6 weeks after infection and were moribund within 2 weeks of the onset of signs, whereas cats infected only with FIV developed much milder self-limiting gross and hematologic abnormalities. Pathologic findings in dually infected cats that died were similar to those observed previously in cats dying from uncomplicated primary FIV infection but were much more widespread and severe. Coinfection of asymptomatic FeLV carrier cats with FIV did not increase the levels of FeLV p27 antigen present in their blood over that seen in cats infected with FeLV alone. The amount of proviral FIV DNA was much higher, however, in dually infected cats than in cats infected only with FIV; there was a greater expression of FIV DNA in lymphoid tissues, where the genome was normally detected, and in nonlymphoid tissues, where FIV DNA was not usually found. Dually infedted cats that recovered from the primary stage of FIV infection remained more leukopenic than cats infected with FIV or FeLV alone, and their CD4+/CD8+ T-lymphocyte ratios were inverted. One of these cats developed what was considered to be an opportunistic infection. It was concluded, therefore, that a preexistent FeLV infection in some way enhanced the expression and spread of FIV in the body and increased the severity of both the resulting transient primary and chronic secondary stages of FIV infection. This study also demonstrated the usefulness of the FIV model in studying the role of incidental infectious diseases as cofactors for immunodeficiency-causing lentiviruses.
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PMID:Feline leukemia virus infection as a potentiating cofactor for the primary and secondary stages of experimentally induced feline immunodeficiency virus infection. 215 26

The principal toxicity of standard induction regimens for acute non-lymphocytic leukemia (ANLL) [including cytarabine (ARA-C) 100 mg/m2 for 7 days plus an anthracycline] is myelotoxicity, leading to death in at least 25% of cases during induction in non-selected patients. The complete remission rate is less than 35% in patients over 65 years of age, due in part to an age-related increase of myelotoxicity. The other important adverse effect of standard-dose cytarabine is gastrointestinal toxicity, especially oral mucositis, diarrhoea, intestinal ulceration, ileus and subsequent Gram-negative septicaemia. Idiosyncratic reactions like exanthema, fever and elevation of hepatic enzymes are relatively frequent, but do not represent therapeutic problems. Intermittent high-dose cytarabine (3 g/m2 in 8 to 12 doses) is extremely myelosuppressive. Similarly, the gastrointestinal toxicity is formidable and dose-limiting. Severe, and sometimes irreversible, cerebellar/cerebral toxicity in 5 to 15% of courses of treatment limits the peak dose of cytarabine. The pathogenesis, prophylactic and therapeutic measures are unknown. These major toxicities are age-related and prohibitive to the use of high-dose cytarabine therapy in patients older than 55 to 60 years. Subacute noncardiogenic pulmonary oedema occurs in some patients, with an incidence of about 20%, and seems to have an intriguing coincidence with precedent streptococcal septicaemia; high-dose systemic steroids may be beneficial. Corneal toxicity is very frequent in high-dose cytarabine therapy but is always reversible. It is largely preventable with prophylactic steroid or 2-deoxycytidine eyedrops. Fever, exanthema and hepatic toxicity have an incidence similar to that in standard dosage. The maximum tolerable cumulated dose of cytarabine is significantly lower when the agent is administered as a continuous infusion, due to myelosuppression and gastrointestinal toxicity. Conversely, continuous infusion may be less neurotoxic. The antileukaemic effect of continuous infusion high-dose cytarabine is less well established. The only significant toxicity of low-dose cytarabine is myelosuppression. Given the generally poor condition of leukaemia patients, low-dose cytarabine therapy is well tolerated, although occasional cases of diarrhoea, reversible cerebellar symptoms, peritoneal and pericardial reactions, and ocular toxicity have been reported. Continuous infusion may be more toxic than the usual intermittent dosage. It is concluded that the toxicity of the standard induction regimen for ANLL is acceptable in patients younger than 60 to 65 years with no concurrent disease. Low dose cytarabine is tolerable for virtually all ANLL patients, but the overall therapeutic efficacy still needs to be defined and compared to standard therapy in the relevant age groups.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The toxicity of cytarabine. 217 34

YNK01 (a daily oral dose of 450 mg) was administered for 22 days to a 58-year-old-female with Ph1-positive acute unclassified leukemia. Leukemia cells were negative for peroxidase and esterase, but were positive for CD19, CD13, CD34, CD9, HAL-DR, CD25, and TdT. Complete remission was obtained and continued for at least a month. The main side effects noted were diarrhea and melena. The administration of YNK01 resulted in plasma ara C levels that ranged between 15.4 to 23.0 ng/ml, which appear to be nearly equivalent to dose achieved during continuous IV infusion of a low dose (20 mg/m2/day) of ara C.
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PMID:[A case of complete remission from acute unclassified leukemia achieved by using a prodrug of ara C, stearyl-ara-CMP (YNK01)]. 223 91


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