Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.
Abdominal Pain/*chemically induced/diagnosis ; Acute Disease ; Diagnosis, Differential ; Fever of Unknown Origin/*chemically induced/diagnosis ; Graves Disease/*drug therapy ; Humans ; Male ; Methimazole/*adverse effects/*therapeutic use ; Middle Aged ; Pancreatitis/*chemically induced/diagnosis ; Treatment Outcome

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.
Abdominal Pain/*chemically induced/diagnosis ; Acute Disease ; Diagnosis, Differential ; Fever of Unknown Origin/*chemically induced/diagnosis ; Graves Disease/*drug therapy ; Humans ; Male ; Methimazole/*adverse effects/*therapeutic use ; Middle Aged ; Pancreatitis/*chemically induced/diagnosis ; Treatment Outcome

The chemotherapy agent L-asparaginase (L-asp) has been an important part of acute lymphoblastic leukemia therapy for over 30 years. It is evident that L-asp has a long-term curative effect. However, L-asp is associated with high incidence of adverse reactions. This has prompted the development of pegylated asparaginase (PEG-asp), which has undergone extensive testing. Apparently, PEG-asp has a prolonged half-life with a better tolerance profile while retaining the antileukemic effect. In this review, we attempt to outline the history of clinical application of L-asp, the pharmacological and clinical potential of various preparations of L-asp, the development of PEG-asp, and the clinical application and adverse events of PEG-asp. The literatures reviewed in this article is collected through online search of the major databases both in English and Chinese.
Antineoplastic Agents ; therapeutic use ; Asparaginase ; adverse effects ; pharmacokinetics ; pharmacology ; therapeutic use ; Blood Coagulation Disorders ; chemically induced ; Humans ; Pancreatitis ; chemically induced ; Polyethylene Glycols ; adverse effects ; pharmacokinetics ; pharmacology ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

OBJECTIVETo analyze the clinical characteristics and the course of diagnosis and therapy of PEG-asparaginase associated pancreatitis (AAP) in childhood, and to reveal the pathophysiology of AAP, enhance the ability of diagnosis and treament.

METHODData of 13 cases with AAP in childhood seen from March 2011 to March 2014 were analyzed with regard to clinical manifestations, laboratory findings, imaging feature and treatment.

RESULTAAP was found in 12 of acute lymphoblastic leukemia (ALL) and 1 of non-Hodgkin's lymphoma (NHL), 8 were boys and 5 were girls, with a mean age 6 years. In 12 cases AAP occurred during the induction-remission treatment, in 1 case during the maintenance- intensification phase. AAP occurred after a median of two doses, and 9 d (median) from the latest administration of PEG-asparaginase. The major manifestations of AAP was abdominal pain (11/13) . At the time of AAP diagnosis during the first 48 hours the median peak serum amylase and serum lipase levels were 559 U/L (range 118-1 585, upper normal limit: 125) and 934 U/L (range 221-1 673, upper normal limit: 300). Three cases with serum amylase and serum lipase levels above 3 times upper normal limit were repeatedly complicated with pancreatic pseudocyst; 11 patients had abnormal CT imaging, 8 cases revealed effusion around the pancreas, and 4 cases had pseudocyst. Therapy with ulinastatin, octreotide acetate, glucocorticoid could relieve abdominal pain significantly. Three cases underwent abdominal puncture drainage and 5 cases fulfilled nasojejunal nutrition therapy. Nine of them were cured, 4 developed pseudocyst, in 2 AAP vanished gradually and 2 died with pseudocyst.

CONCLUSIONThe major manifestations of AAP were abdominal pain, but sometimes apparent and sometimes latent. Condition of acute pancreatitis may exacerbate rapidly and easily. Early identification had significance. Pancreatic pseudocyst suggested a poor prognosis.

Acute Disease ; Asparaginase ; adverse effects ; therapeutic use ; Child ; Female ; Humans ; Lymphoma, Non-Hodgkin ; drug therapy ; Male ; Pancreatic Pseudocyst ; Pancreatitis ; chemically induced ; diagnosis ; therapy ; Polyethylene Glycols ; adverse effects ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

OBJECTIVETo investigate the effect of resveratrol on the apoptosis of pancreatic acinar cells in rats with severe acute pancreatitis (SAP) and explore the mechanism of such effect.

METHODSD rats with 3.5% sodium taurocholate-induced SAP were treated with resveratrol, and the serum amylase was detected with automatic biochemistry analyzer. The apoptosis of the pancreatic acinar cells in the rats was detected by TUNEL assay, and the expression of Fas and FasL genes was determined by RT-PCR and Western blotting. The pathological changes of the pancreas were observed under optical microscope.

RESULTSCompared with SAP group, the resveratrol-treated rats showed obviously decreased serum amylase and scores for pancreatic histopathological lesions. Resveratrol treatment significantly increased the apoptotic indices of pancreatic acinar cells and the levels of FasL mRNA and protein in rats with SAP.

CONCLUSIONResveratrol produces important therapeutic effect on SAP in rats by inducing pancreatic acinar cell apoptosis possibly as a result of up-regulated FasL gene expression.

Animals ; Apoptosis ; drug effects ; Fas Ligand Protein ; drug effects ; genetics ; metabolism ; Male ; Pancreas, Exocrine ; pathology ; Pancreatitis, Acute Necrotizing ; chemically induced ; drug therapy ; pathology ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; therapeutic use ; Taurocholic Acid ; Up-Regulation

Oral 5-aminosalicylic acid (5-ASA) has been known as a first-choice drug for ulcerative colitis. However, hypersensitivity reactions, including pancreatitis, hepatitis, and skin rash, have been reported with 5-ASA. Topical formulations of 5-ASA like suppositories have been rarely reported to induce adverse reactions because of their limited absorption rate. We recently experienced a case of acute pancreatitis caused by 5-ASA suppositories in a patient with ulcerative colitis. A 26-year-old male was admitted with abdominal pain and diagnosed as ulcerative colitis. Acute pancreatitis occurred soon after 24 hours of treatment with oral mesalazine. Drug-induced pancreatitis was suspected and administration of mesalazine was discontinued. Then 5-ASA suppositories were started instead of oral mesalazine. Twenty-four hours after taking 5-ASA suppositories, he experienced severe abdominal pain, fever, and elevation of amylase levels. The suppositories were immediately stopped and symptoms resolved over next 48 hours. Herein, we suggest that, in patients treated with 5-ASA suppositories who complain of severe abdominal pain, drug-induced pancreatitis should be suspected.
Acute Disease ; Adult ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage/*adverse ; Colitis, Ulcerative/diagnosis/*drug therapy ; Humans ; Male ; Mesalamine/administration & dosage/*adverse effects/therapeutic use ; Pancreatitis/*chemically induced/*diagnosis ; Suppositories ; Tomography, X-Ray Computed

Acute pancreatitis is a serious disease with fatality rate up to 15%. We recently experienced a case of acute pancreatitis induced by multiple drugs in a patient with ulcerative colitis. A 20-year-old female visited with abdominal pain and hematochezia and diagnosed of ulcerative colitis. Sulfasalazine and prednisolone were used. However, acute pancreatitis occurred after 4 weeks of treatment with additional azathioprine treatment. Drug-induced pancreatitis was suspected, and she was recovered with conventional therapy for acute pancreatitis. Therefore, it was proposed that acute pancreatitis was induced by azathioprine. However, after the administration of sulfasalazine, pancreatitis relapsed. Furthermore, even the re-administration of 5-ASA and azathioprine induced relapse of acute pancreatitis. We concluded that acute pancreatitis was induced by multiple drugs in this patient with ulcerative colitis.
Acute Disease ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Antimetabolites/adverse effects ; Azathioprine/adverse effects ; Colitis, Ulcerative/diagnosis/*drug therapy ; Colonoscopy ; Female ; Humans ; Mesalamine/adverse effects ; Pancreatitis/*chemically induced/*diagnosis ; Sulfasalazine/adverse effects ; Tomography, X-Ray Computed ; Young Adult

BACKGROUND/AIMS: Ciprofloxacin is considered to be a safe and effective treatment for acute infectious colitis. However, this drug may cause drug-induced pancreatitis, albeit rarely. METHODS: From March 2007 to February 2012, we studied 227 patients who were hospitalized for infectious colitis at St. Mary's Hospital. All of the patients received ciprofloxacin therapy for the treatment of infectious colitis. We observed a few cases of rare adverse events, including ciprofloxacin-induced acute pancreatitis diagnosed based on the Naranjo algorithm. RESULTS: During ciprofloxacin therapy, seven of 227 patients (3.1%) developed rare pancreatitis as defined by the Naranjo algorithm; pancreatic enzyme activity was sporadically elevated with ciprofloxacin use. After ciprofloxacin administration, the average interval until the development of pancreatitis was 5.5 days (range, 4 to 7 days). On abdominal computed tomography, pancreatic swelling and homogenous enhancement was noted in three of seven patients. Complicating acute pancreatitis was gradually but completely resolved after cessation of ciprofloxacin administration. The mean recovery time was 11.3 days (range, 8 to 15 days). CONCLUSIONS: We observed that ciprofloxacin-induced pancreatitis may occur with an incidence of approximately 3%. Ciprofloxacin-induced pancreatitis presents a short latency, suggesting an idiosyncratic hypersensitivity reaction. Practitioners should be aware that drug-induced pancreatitis can occur during ciprofloxacin therapy.
Acute Disease ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*adverse effects ; Bacterial Infections/*drug therapy ; Ciprofloxacin/*adverse effects ; Colitis/*drug therapy ; Enzyme Inhibitors/therapeutic use ; Female ; Gabexate/analogs & derivatives/therapeutic use ; Humans ; Male ; Middle Aged ; Pancreatitis/*chemically induced/drug therapy ; Young Adult

A 21-year-old man admitted complaining of sudden severe epigastric pain for 1 day. He had been diagnosed as ulcerative colitis (UC) and taking mesalazine for two months. UC was in nearly complete remission at admission. He never drank an alcohol, and serum amylase was 377 IU/L. CT scan showed inferior vena cava (IVC) thrombosis in addition to mild acute pancreatitis. To evaluate the cause of acute pancreatitis and IVC thrombosis, magnetic resonance cholangiopancreatogram (MRCP), endoscopic ultrasonogram (EUS), lower extremity Doppler ultrasonogram (US) and blood test of hypercoagulability including factor V, cardiolipin Ab, protein C, protein S1, antithrombin III, and anti phospholipids antibody were performed. There was no abnormality except mild acute pancreatitis and IVC thrombosis in all the tests. He was recommended to stop taking mesalazine and start having anticoagulation therapy. After all symptoms disappeared and amylase returned normal, rechallenge test with mesalazine was done. Flare-up of abdominal pain occurred and the elevation of serum amylase was observed. Ulcerative colitis came to complete remission with short-term steroid monotherapy. Acute pancreatitis and IVC thrombosis were completely resolved after 3-month anticoagulation therapy with no more mesalazine. We postulated that IVC thrombosis occurred due to hypercoagulable status of UC and intra-abdominal inflammation caused by mesalazine-induced pancreatitis.
Acute Disease ; Amylases/blood ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects/therapeutic use ; Anticoagulants/therapeutic use ; Cholangiopancreatography, Magnetic Resonance ; Colitis, Ulcerative/complications/*diagnosis/drug therapy ; Endosonography ; Humans ; Male ; Mesalamine/*adverse effects/therapeutic use ; Pancreatitis/chemically induced/*diagnosis/ultrasonography ; Tomography, X-Ray Computed ; Ultrasonography, Doppler ; *Vena Cava, Inferior/ultrasonography ; Venous Thrombosis/complications/*diagnosis/drug therapy ; Young Adult

BACKGROUND/AIMS: To investigate the expression of Toll-like receptor 4 (TLR4) in the pancreases of rats with acute necrotizing pancreatitis (ANP) and any changes upon treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB (NF-kappaB), as well as to determine the relationship between TLR4 and NF-kappaB in ANP pathogenesis. METHODS: A total of 72 SD rats were randomly divided into three groups, namely, the control (sham-operation), ANP, and ANP with PDTC pretreatment groups. The PDTC-pretreated group was intraperitoneally injected with PDTC at a dose of 100 mg/kg 1 hour before the induction of ANP. The expressions of TLR4 and NF-kappaB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 were measured by reverse transcription polymerase chain reaction. RESULTS: The expressions of TLR4, NF-kappaB, and cytokine (NF-kappaB target) genes in the pancreatic tissue increased more significantly in the ANP groups than in the sham-operation group at 3, 6, and 12 hours. Pretreatment with PDTC alleviated the inflammatory activation in the pancreas with ANP, causing a significant decrease in the expressions of TLR4, NF-kappaB, and cytokine genes in the pancreatic tissue. CONCLUSIONS: The expressions of TLR4 and NF-kappaB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-kappaB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.
Animals ; Antioxidants/*pharmacology ; Interleukin-1beta/genetics/metabolism ; Interleukin-6/genetics/metabolism ; Male ; NF-kappa B/*drug effects/metabolism ; Pancreas/metabolism/pathology ; Pancreatitis, Acute Necrotizing/chemically induced/*drug therapy ; Pyrrolidines/*pharmacology ; RNA, Messenger/metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thiocarbamates/*pharmacology ; Toll-Like Receptor 4/*drug effects/metabolism ; Tumor Necrosis Factor-alpha/genetics/metabolism