Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report 9 cases of acute non traumatic pancreatitis in children. The most common symptom in their patients is atypical abdominal pain often associated with vomiting (5 cases) and shock (4 cases). Among laboratory investigations: --High serum amylase level (average: 1 045 UI/l) is constant, associated with hypocalcemia and hyperglycemia in 3 patients. --Radiographic findings on plain film of the abdomen are diagnostic in 4 cases. --Abdominal ultrasound is the most reliable test and positive in the only patient on which performed. Among etiologies, drug induced pancreatitis is the most common (5 cases) due to combined Prednisone-L-Asparaginase (4 patients): --A duodenal ulcer and a case of choletithiasis are reported. --In 2 patients no determinant factors are found. A good response to parenteral nutrition, gastric suction and antisecretory agents is observed in 7 cases. 2 leukemic patients died shortly after the acute episode.
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PMID:[Acute non-traumatic pancreatitis in childhood. Report of 9 cases (author's transl)]. 746 Jan 9

L-Asparaginase-induced pancreatitis is an uncommon but potentially lethal complication. An 8-year-old girl with acute lymphoblastic leukaemia developed acute pancreatitis following treatment with asparaginase. Clinical and laboratory improvements were evident after treatment with somatostatin, with no complications of pancreatitis. Induction therapy for the leukaemia was able to be continued and complete remission was documented during the course of pancreatitis and somatostatin treatment, suggesting a beneficial role of somatostatin in the management of asparaginase-induced pancreatitis.
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PMID:Somatostatin therapy in L-asparaginase-induced pancreatitis. 790 15

The incidence of pancreatitis in patients with haematopoetic neoplasms who are treated with L-asparaginase is fom 2 to 24%. In majority of cases the pancreatitis is oedematous and self-limiting. Acute haemorrhagic or necrotizing pancreatitis caused by L-asparaginase is rare but potentially life-threatening complication. We present 2 cases of acute pancreatitis in children aged 2 and 4 years. They were diagnosed to have acute lymphoblastic leukaemia and were treated according to the ALLLIC BFM 2002 protocol. Acute pancreatitis developed in these children after induction therapy and was followed by formation of a pseudocyst. In both cases the diagnosis of this complication was made directly after phase I of the protocol I (after eighth dose of L-Asparaginase). In the first case the course of acute pancreatitis was mild. Normalization of the amylase levels occurred after 7 days and the diagnosis of post inflammatory cyst was made 15 days after the first signs of the disease. But thereafter, during the additional complication (pneumonia with Pseudomonas aeruginosa bacteriemia) the pancreatic cyst became infected. In the second case acute pancreatitis had a severe course and the child required treatment in the Intensive Care Unit for 21 days. The cyst was diagnosed after 20 days from the beginning of symptoms. The surgical procedure, applied in both cases was internal drainage by anastomosis of the cyst with the back wall of the stomach. Antileukaemic treatment was recommenced after 6-8 weeks when complications resolved. Currently both children are well and remain in haematological remission and continue maintenance chemotherapy.
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PMID:[Acute pancreatitis during chemotherapy of acute lymphoblastic leukaemia complicated with pseudocyst]. 1953 25

L-Asparaginase is an effective drug in childhood acute lymphoblastic leukemia (ALL) and it has become an important component of most childhood ALL regimens with administration in induction, intensification, and maintenance phases of treatment. L-Asparaginase is associated with side effects occurring either in a dose or time-dependent fashion or as hypersensitivity reactions. Some well-known toxicities in asparaginase-containing regimens are hypersensitivity/allergy and thromboembolic events. When asparaginase and steroids are used together, mild hyperlipemia is reasonably common. As some published studies show, this abnormality is often underdiagnosed. Hyperlipemia rarely constitutes a clinical problem; however, when triglyceride elevation is greater than 1000 mg/dL, the risk of pancreatitis is increased. We report the case of a young female presenting with acute severe hypertriglyceridemia (9250 mg/dL) during intensification phase of ALL, with neurologic symptoms but without the development of pancreatitis. She was successfully managed with 1 single run of plasmapheresis.
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PMID:L-Asparaginase and steroids-associated hypertriglyceridemia successfully treated with plasmapheresis in a child with acute lymphoblastic leukemia. 2139 28

Acute lymphoblastic leukaemia (ALL) is one of the leading types of malignant disorder seen in children. Viral infections, genetic factors and exposure to chemical carcinogens are some of the factors responsible for causing ALL. Treatment strategies followed for curing ALL include chemotherapy or radiation therapy, wherein, chemotherapy involves the use of the enzymatic drug L-Asparaginase. The enzyme can be produced from various plants, animals, bacterial and fungal sources but, among them, bacterial sources are widely used for production of this enzyme. The enzyme is non-human in origin having certain bottle necks with L-Asparaginase therapy in the form of side effects such as pancreatitis, thrombosis which are mainly due to glutaminase side activity. Hence, present-day research is mainly focussed on minimizing or completely eliminating the glutaminase activity of the enzyme L-Asparaginase. This review is focussed on the complications associated with glutaminase side activity and use of glutaminase free enzymatic drug L-Asparaginase in treating ALL and the other developments related to the modification of the drug for quality treatment.
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PMID:L-Asparaginase as potent anti-leukemic agent and its significance of having reduced glutaminase side activity for better treatment of acute lymphoblastic leukaemia. 2268 10

L-Asparaginase (EC3.5.1.1) is an enzyme, which is used for treatment of acute lymphoblastic leukaemia (ALL) and other related blood cancers from a long time. This enzyme selectively hydrolyzes the extracellular amino acid L-asparagine into L-aspartate and ammonia, leading to nutritional deficiencies, protein synthesis inhibition, and ultimately death of lymphoblastic cells by apoptosis. Currently, bacterial asparaginases are used for treatment purpose but offers scepticism due to a number of toxicities, including thrombosis, pancreatitis, hyperglycemia, and hepatotoxicity. Resistance towards bacterial asparaginase is another major disadvantage during cancer management. This situation attracted attention of researchers towards alternative sources of L-asparaginase, including plants and fungi. Present article discusses about potential of L-asparaginase as an anticancer agent, its mechanism of action, and adverse effects related to current asparaginase formulations. This article also provides an outlook for recent developments in L-asparaginase discovery from alternative sources and their potential as a less toxic alternative to current formulations.
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PMID:Recent developments in L-asparaginase discovery and its potential as anticancer agent. 2563 Jun 63

Acute pancreatitis in children acute lymphoblastic leukemia is commonly caused by drugs, for example, L-Asparaginase, pegapargase, steroids. The incidence of this complication is estimated at 6.7% to 18%. Although the majority of drug-induced acute pancreatitis cases are mild, severe cases can rarely occur. This work presents a case of successful management of a child with drug-induced necrotizing pancreatitis during acute lymphoblastic leukemia therapy. This case illustrates that comprehensive care and immediate intensive treatment can rescue patient despite poor prognosis. Administration of octreotide may serve a role in limiting the severity of the disease.
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PMID:Successful Management of a Child With Drug-induced Necrotizing Pancreatitis During Acute Lymphoblastic Leukemia Therapy: A Case Report. 2968 55

L-Asparaginase has significantly improved outcome for children with acute lymphoblastic leukemia and has become an essential component of multiagent chemotherapy. However, there are many adverse events due to L-asparaginase, including acute pancreatitis. The pathology of L-asparaginase-associated pancreatitis (AAP) remains unclear. We compared patients who developed AAP (n=29) and random matched controls (n=36) who had been enrolled in the Japan Association of Childhood Leukemia Study of the ALL-02 protocol. AAP and control patients were matched for age, sex, treatment, and protocol risk. We examined correlations between AAP development and clinical symptoms, laboratory data, and concomitant medication. Abdominal pain and nausea were common presenting symptoms for AAP. There was an increased risk of AAP in patients using gastric acid-suppressing agents and antithrombin (AT) supplementation. Mean fibrinogen and AT levels before the onset of AAP were lower in AAP patients than in controls. Decreased AT and fibrinogen levels resulting from the strong suppression of protein synthesis by L-asparaginase were predictive signs for AAP. Our epidemiological approach should prove clinically useful for the diagnosis the AAP as early as possible.
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PMID:Acid-suppressing Drugs and a Low 1 Level of Antithrombin as Risk Factors for L-Asparaginase-associated Pancreatitis: A Case-control Study in the Japan Association of Childhood Leukemia Study (JACLS). 2969 79

L-Asparaginase is an enzyme successfully being used in the treatment of acute lymphoblastic leukemia, acute myeloid leukemia, and non-Hodgkin's lymphoma. However, some disadvantages still limit its full application potential, e.g., allergic reactions, pancreatitis, and blood clotting impairment. Therefore, much effort has been directed at improving its performance. A popular strategy is to randomly conjugate L-asparaginase with mono-methoxy polyethylene glycol, which became a commercial FDA approved formulation widely used in recent years. To improve this formulation by PEGylation, herein we performed cysteine-directed conjugation of the L-asparaginase subunits to prevent dissociation-induced loss of activity. The recombinant cysteine conjugation sites were introduced by mutagenesis at surface-exposed positions on the protein to avoid affecting the catalytic activity. Three conjugates were obtained using different linear PEGs of 1000, 2000, and 5000 g/mol, with physical properties ranging from a semi-solid gel to a fully soluble state. The soluble-conjugate exhibited higher catalytic activity than the non-conjugated mutant, and the same activity than the native enzyme. The cysteine-directed crosslinking of the L-asparaginase subunits produced a higher molecular weight conjugate compared to the native tetrameric enzyme. This strategy might improve L-asparaginase efficiency for leukemia treatment by reducing glomerular filtration due to the increase in hydrodynamic size thus extending half-live, while at the same time retaining full catalytic activity.
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PMID:Thiol-maleimide poly(ethylene glycol) crosslinking of L-asparaginase subunits at recombinant cysteine residues introduced by mutagenesis. 3005 38