Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A nine-year old girl with T cell acute lymphoblastic leukemia (ALL) had acute severe neurologic complications at the end of the remission-induction chemotherapy course. Thirty-six hours following triple intrathecal (IT) therapy and intravenous (IV) administration of L-asparaginase (L-asp), tetraplegia developed and she became unconscious. She had bouts of hypertension and persistent tachycardia unresponsive to digitalis therapy. Magnetic resonance imaging (MRI) showed multiple brain white matter hyperintensities and filling defects in the saggital sinus, suggesting thrombosis. Over the 40 days, in addition to her neurologic compromise she also had transient diabetes mellitus, severe hyperlipidemia, hypoproteinemia and edema, liver and heart failure and staphylococcus aureus sepsis with prolonged bone marrow depression. Despite, coexistence of all these chemotherapy related complications, her neurologic functions and multiple organ failure improved gradually. After a 70 days' period of interruption, chemotherapy was resumed and continued without any further complications. Although, the etiology of her extensive sensitivity to some drugs remains unclear, we believe that it is important to document these unusual events in this child.
 ...
PMID:Coexistence of life threatening chemotherapy related leukoencephalopathy, saggital sinus thrombosis and multiple organ failure in a child with acute lymphoblastic leukemia: an unusual case with clinical recovery. 932 1

Hyperglycemia in children with acute lymphoblastic leukemia (ALL) has been well documented in the literature. The purpose of the present study was to evaluate the clinical value of glycated hemoglobin (GHb) and fructosamine (Frc) in the long-term glycemic control of ALL patients. An attempt was made to identify the risk factors for hyperglycemia in ALL patients. The study group comprised 26 newly diagnosed ALL patients admitted to hospital during 1995-96. Patients with a history of blood transfusion or infection within the past 3 months were excluded from the study. White blood cell (WBC) counts, fasting blood glucose (FBG), GHb and Frc levels were analyzed in venous blood on screening day 0, before induction of chemotherapy. Frc analysis was repeated on the 21st day and GHb level on the 60th day of chemotherapy. FBG tests were performed before each dose of L-asparaginase, on days 21 and 60. None of the patients was obese. Although six children (23%) had hyperglycemia during the induction therapy, four of them had a GHb level higher than normal on admission. Only one patient who developed hyperglycemia had a family history of diabetes mellitus. Patients with a high initial WBC count (> 20 x 10(9)/L) had a significantly higher baseline GHb than patients with a WBC count below this level. GHb values returned to normal after achievement of complete remission. It is suggested that the leukemic process could impair glucose metabolism and baseline GHb may be used to monitor possible small changes in glucose homeostasis of ALL patients, prior to chemotherapy.
 ...
PMID:Clinical value of glycated hemoglobin and fructosamine in the long-term glycemic control of children with acute lymphoblastic leukemia. 958 1

From January 1994 until May 1997, 54 children with leukemia and non Hodgkin lymphoma were analyzed. The enzymatic function and ultrasound examination of pancreas were estimated. In 17 of 54 patients the clinical symptoms suggesting pancreatitis or toxic lesion of pancreas were observed. In 13 cases L-asparaginase was administered. The main symptom of the pancreas disease was severe abdominal pain with vomiting. The typical ultrasound view of pancreatitis was observed in 4 cases, pancreas oedema was seen in 6 patients. The most serious course of pancreatitis was diagnosed in 3 children. Diabetes mellitus coexisted in two cases, in the third case osteoporosis was seen. Because of the toxic pancreas lesion in one patient the administration of L-asparaginase and cortical hormones was discontinued, in the remaining 2 children the therapeutic scheme was modified. In all 17 cases this side effect was completely reversible, as well as in 3 children with the most serious clinical course of pancreas lesions.
 ...
PMID:[Clinical manifestation of toxic pancreas lesion in children with hematopoietic malignancies]. 1073 49

Asparaginase is an enzyme used in the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma in children. It has minimal bone marrow toxicity. Its major side effects are anaphylaxis, pancreatitis, diabetes, coagulation abnormalities, and thrombosis, especially intracranial. It is derived from 2 different sources: Escherichia coli and Erwinia chrysanthemi. Nonrandomized clinical studies have suggested a similar efficacy of these 2 types of asparaginases and a lower toxicity for Erwinia-asparaginase. The European Organisation for Research and Treatment of Cancer-Children's Leukemia Group (EORTC-CLG) 58881 trial randomized 700 children with acute lymphoblastic leukemia or lymphoblastic lymphoma to either E coli- or Erwinia-asparaginase at the same dosage of 10 000 IU/m(2) twice weekly to compare toxicity and efficacy. Coagulation abnormalities were more frequent in the E coli-asparaginase than in the Erwinia-asparaginase arm of the study (30.2% versus 11.9%, P <.0001). The incidence of other toxicity was not significantly different. In the Erwinia-asparaginase arm, more patients failed to achieve complete remission (4.9% versus 2.0%; P =.038) and the relapse rate was higher, leading to shorter event-free survival (hazard ratio,1.59; 95% CI, 1.23-2.06; P =.0004). The estimate of event-free survival rate (SE) at 6 years was 59.8% (2.6%) versus 73.4% (2.4%). Overall survival rate at 6 years was also lower in the Erwinia-asparaginase arm at 75.1% (2.3%) versus 83.9% (2.0%), P =.002. With the dose scheduling used in this protocol, E coli-asparaginase induced more coagulation abnormalities but was superior to Erwinia-asparaginase for the treatment of childhood lymphoid malignancies.
 ...
PMID:Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children's Leukemia Group phase 3 trial. 1192 60

To identify risk factors associated with the development of diabetes mellitus and to describe the prevalence of diabetes in pediatric hematopoietic cell transplant (HCT) survivors. The follow-up records of 748 patients who survived for at least 2 years after pediatric HCT were retrospectively reviewed for diagnosis of diabetes. Risk factors for type 2 diabetes were analyzed using multivariate statistics. Among 748 patients with a median of 11 years of follow-up, 38 developed diabetes after HCT. Four patients (three leukemia and one neuroblastoma) developed type 1 diabetes 8 to 14 years after HCT, at between 10 and 19 years of age. Thirty-four patients (32 leukemia and 2 aplastic anemia) developed type 2 diabetes 1 to 24 years after HCT, at between 11 and 41 years of age. Of the 34 patients with type 2 diabetes, 23 were non-Hispanic white, 3 had experienced asparaginase toxicity (hyperglycemia and/or pancreatitis), and 26 had a family history of diabetes. Risk factors associated with type 2 diabetes were diagnosis of acute or chronic leukemia, race/ethnicity other than non-Hispanic white, family history of diabetes, and asparaginase toxicity. The prevalence of type 1 diabetes among all surviving patients was 0.52%, or three times higher than the general U.S. population. The prevalence of type 2 diabetes was 9% among leukemia survivors and 2% among aplastic anemia survivors, both higher than expected. Pediatric HCT survivors are more likely to develop diabetes than the general population.
 ...
PMID:Diabetes mellitus in long-term survivors of pediatric hematopoietic cell transplantation. 1476 93

Growth Hormone Releasing Hormone (GHRH) is one of the most important hormones in life. Because of its potential clinical importance, its short half-life, and its expensive chemical synthesis, an analog of hGHRH with a prolonged half-life and better activity has been studied for clinical application, especially for the treatment of muscle wasting, type II diabetes, or sleep disorders. The Pro-Pro-hGHRH(1-44) peptide has better activity. The fusion partner gene with 127 amino acid residues of the C-terminus from l-asparaginase was recombined with asp-pro-pro-hGHRH(1-44) gene synthesized by PCR method to form a fusion protein with the unique acid labile linker Asp-Pro. The recombinant protein was expressed to high levels in Escherichia coli BL21 (DE3). The Pro-Pro-hGHRH(1-44) peptide was purified to homogeneity by means of cell disruption, washing, ethanol precipitation, acid hydrolysis, and SP-Sephadex C-25, and Sephadex G-25 column chromatography. The fold of the purification was about 88 times and the yield was 1.1% of the total protein weight of the inclusion body. The peptide molecular mass of 5235.25 Da was determined by ESI mass spectroscopy. Its purity was determined by SDS-PAGE. In the study of the activity, we measured GH release of rat pituitary by using the antiserum kit against human GH. The peptide doses of 0.01, 0.1, 1.0, 7.72, and 20.9 microg/ml used, respectively, released the GH values of 0.1+/-0.1, 12.5+/-7.3, 16.6+/-5.8, 49.8+/-7.6, and 79.5+/-5.7 ng/ml whereas their blank controls, respectively, were 0.5+/-0.8, 4.1+/-2.6, 3.1+/-3.1, 4.7+/-1.8, and 1.2+/-0.3 ng/ml. The activity results of all dose groups except 0.01 microg/ml Pro-Pro-hGHRH(1-44) group and hGHRH(1-40) group showed that there were significant differences between GH released by the peptide and that by its blank control. With the increase of dosage, the differences were more significant. hGHRH(1-40) showed no measured GH release when the dose was up to 2 microg/ml. The activity results show that the Pro-Pro-hGHRH(1-44) peptide is a potential GH releasing analog.
 ...
PMID:Production and enhanced biological activity of a novel GHRH analog, hGHRH with an N-terminal Pro-Pro extension. 1500 64

Treatment of hematological malignancies with L-asparaginase has been associated with diabetes mellitus in about 1-2% of patients. The concomitant use of steroids has an additional deleterious effect. In this article, we report the occurrence of diabetes in a 13 year-old girl treated with L-asparaginase and dexamethasone for acute lymphoblastic leukemia. The diabetes developed 120 days after the drug was started, requiring insulin therapy for 12 months. Anti-islet autoantibody was negative, and there were no laboratory findings suggestive of pancreatitis. The DM related do L-asparaginase therapy is insulinopenic and transient, resolving with suspension of the drug. The diagnosis of this type of diabetes is based on its temporal relationship with the L-asparaginase and in the exclusion of other known causes. There is no laboratory test capable of elucidating the diagnosis. Therefore, investigation to rule out type 1A DM, type 1B DM, insulin-resistant DM induced by corticotherapy and DM secondary to toxic pancreatitis is of utmost importance. The insulin therapy must be followed closely, since this is a transient form of diabetes.
 ...
PMID:[Transient diabetes mellitus related to L-asparaginase therapy]. 1768 27

Antitumor and immunosuppressant treatment-related neurotoxicity can determine nonspecific clinical syndromes. Exclusion of other possible causes, among which tumor progression, appearance of paraneoplastic disease, renal or hepatic failure, diabetes or hypertension, is relevant. We report clinical and neuroradiological features in five patients with neurotoxic syndromes due to chemotherapy/radiotherapy or immunosuppression in the context of neoplastic disease/organ transplantation. Acute neurological syndrome developed in three patients after methotrexate (MTX), cyclosporine A, and L-asparaginase therapy, respectively. MRI showed posterior reversible encephalopathy in two cases and venous thrombosis with intraparenchymal hematoma in the third patient. Late onset clinical syndrome occurred in the last two patients, treated with MTX or radiation therapy for breast cancer metastasis and pituitary adenoma. Neuroimaging showed brain diffuse abnormalities. Patients affected by tumors suffer from increased risk for treatment-related toxicities. Appearance or worsening of neurological signs and symptoms challenge the clinician to discriminate between CNS involvement by the tumor, toxicity of drugs, parane-oplastic disease and infections. MRI has a key role in differential diagnosis. Close interaction between the neurologist, the oncologist and the neuroradiologist leads to the optimal management of patients.
 ...
PMID:Clinical and radiological features of brain neurotoxicity caused by antitumor and immunosuppressant treatments. 1861 59

Little is known about octreotide therapy in asparaginase-associated pancreatitis (AAP) in children. Of the 59 children with acute lymphoblastic leukemia (ALL) receiving E. coli L-asparaginase, 5 patients (8.5%) developed AAP. Octreotide was administered to four patients. Clinical and laboratory improvement were evident after octreotide therapy. There were no deaths and no severe adverse side effects were noted. No pseudocysts were detected; however, two of the four patients developed diabetes. One child without octreotide treatment developed chronic pancreatitis and pseudocyst. We conclude that octreotide therapy appears to be safe and potentially beneficial in the management of AAP in children.
 ...
PMID:Octreotide therapy in asparaginase-associated pancreatitis in childhood acute lymphoblastic leukemia. 1872 19

This study was purposed to investigate the possible side effects of L-asparaginase (L-ASP) in the treatment of patients with acute lymphoblastic leukemia (ALL) and to explore the correlation of these side effects at different therapeutic stages by means of retrospective analysis, so as to reduce the incidence of side effects and improve the safety of chemotherapy and the long-term survival of patients. The probability and severity of side effects related to use of L-ASP in 38 cases of ALL during remission induction therapy (VDLDex regimen) and 40 cases of ALL during maintenance intensive therapy (VMLDex regimen) were compared. The results showed that allergic response, diabetes and drug-induced liver disease happened more frequently during maintenance therapy than during remission induction therapy, while defibrination, abnormal hemagglutinin, acute pancreatitis, hypoproteinemia, gastrointestinal reaction and infectious shock were observed more during remission induction therapy than those at maintenance therapy. In conclusion, the L-ASP showed some side effects especially for the patients during the remission induction therapy which should be paid enough attention. The regular and comprehensive monitoring can effectively reduce and avoid the side effects of L-ASP, to improve the safety of chemotherapy.
 ...
PMID:[Side effects of L-asparaginase during therapies for remission induction and maintenance in children with acute lymphocytic leukemia]. 1954 98


<< Previous 1 2 3 Next >>