1/11. Anticholinergic toxicity associated with lupine seeds as a home remedy for diabetes mellitus.We describe a case of sparteine intoxication associated with using a preparation from lupine seeds. A female patient of Portuguese origin presented to the emergency department with classic anticholinergic signs after ingestion of a lupine seed extract. She took the preparation with the belief it represented a cure for her recently diagnosed diabetes. Analysis of the patient's lupine bean extract identified the preponderant compound as oxo-sparteine by gas chromatography/mass spectrometry. Intoxication by lupine seeds rarely occurs in human beings. To our knowledge, no medical or toxicologic evidence supports a belief that lupine extract could lower serum glucose levels. This case highlights the need for emergency care providers to be aware of the health hazards that can be associated with the use of such home remedies.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
2/11. Falsely increased HbA1c values by HPLC and falsely decreased values by immunoassay lead to identification of Hb Okayama and help in the management of a diabetic patient.A falsely increased HbA1c value of 47.1% was determined by cation exchange chromatography during a routine HbA1c measurement of the blood sample from a 63-year-old diabetic male patient living in Hamburg, germany. In former determinations by immunological assays falsely decreased values in the range of 5.0 to 5.5% were obtained. The sample was inconspicuous in alkaline hemoglobin electrophoresis. But acid hemoglobin electrophoresis confirmed the falsely increased value. These facts let us consider the existence of a heterozygous "silent hemoglobin variant", such as hemoglobin Okayama, with an amino acid substitution in one of the first four amino acids of the beta chain, representing the epitope of common immunoassays. dna analyses confirmed this presumption and we found the heterozygous mutation hemoglobin Okayama [beta 2 (NA 2) His (CAC)-->Gln (CAA)]. Knowing that an immunological assay only detects about half of the present HbA1c, the obtained values can be used for therapeutic management of this diabetic patient.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
3/11. Haemoglobin Marseille-Long Island and interpretation of HbA1c: which HbA1c result is the "right answer"?A woman was screened for diabetes using glycated haemoglobin (HbA1c). Vastly different results were obtained by high performance liquid chromatography (45%), immunoassay (2.9%), and affinity chromatography (4.2%) compared with the non-diabetic range of less than 6.4%. Mass spectral studies confirmed the presence a haemoglobin variant, haemoglobin Marseille-Long Island which had confounded interpretation by all methods.- - - - - - - - - - ranking = 2keywords = chromatography (Clic here for more details about this article) |
4/11. Unreliable estimation of HbA due to the presence of Camperdown haemoglobin [beta 104 (G6) Arg --> Ser].AIMS: To suggest the possible unreliability of HbA(1c) determination in presence of haemoglobin variants during routine metabolic evaluation. methods: We present a case of Camperdown haemoglobin, accidentally detected in a middle-aged Italian man during routine metabolic evaluation for newly diagnosed diabetes. The haemoglobin variant has been identified by exchange high performance liquid chromatography (CE-HPLC) (VARIANT trade mark HbA(1c) Program, Bio-Rad laboratories, Hercules, CA, USA), and characterized at molecular level by direct sequencing. RESULTS: A 56-year-old male of Northern Italian origin, presented to our centre for a Type 2 diabetes mellitus of recent diagnosis. HbA(1c) determination was routinely determinated. The patient's chromatogram showed an inappropriate peak of 38.5% in the HbA(1c) position suggestive for the presence of abnormal haemoglobin. Further evaluation identified an abnormal haemoglobin peak even higher (49.5%) eluting at 1.34 minutes in P2-window. Molecular characterization of the mutation showed a nucleotide replacement, AGG --> AGC at codon 104, causing the amino acid replacement Arg --> Ser at position 104 (G6) that give rise to Hb Camperdown. CONCLUSIONS: Haemoglobinopathies can lead to inaccurate glycated haemoglobin level determination. In patients carrying haemoglobin variants, the different methods for determinations of glycated haemoglobin could result in different errors, showing either higher or lower values than expected.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
5/11. A new alpha chain variant, Hb Turriff [alpha 99(G6)LysGlu]: the interference of abnormal hemoglobins in Hb A1c determination. Hb Turriff is a new hemoglobin variant which we have identified in a diabetic individual. During the determination of Hb A1c by high performance liquid chromatography, an inappropriately elevated result was found to be due to the abnormal hemoglobin chromatographing with the Hb A1c fraction. This new hemoglobin variant, Hb Turriff [alpha 99(G6)Lys Glu], is not associated with any hematological disturbance, and family investigations indicate that it has arisen as a de novo mutation.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
6/11. False elevation of hemoglobin A1 by hereditary persistence of fetal hemoglobin.Measurement of glycosylated hemoglobin (HgA1) is frequently helpful in the management of patients with diabetes mellitus as it provides an index of average glucose control over the previous two to three months. The present case of a diabetic patient with a markedly increased hemoglobin A1 to 42% (normal 5.2-9.2%) with good glucose control prompted an investigation into the etiology of the increased hemoglobin A1 levels. Hemoglobin electrophoresis revealed that the patient had hereditary persistence of fetal hemoglobin. Hemoglobin F was quantitated and found to be responsible for 73% of the hemoglobin A1 determination. Hemoglobin F co-migrates with hemoglobin A1 on column chromatography and, when present in increased quantities, can falsely elevate the measured hemoglobin A1. Thus, if one utilizes the hemoglobin A1 assay to help guide management of patients with diabetes mellitus, it is important to remember that hemoglobin F can cause falsely elevated hemoglobin A1 levels.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
7/11. Hb hope, beta 136(H14)GlyAsp, in a diabetic Japanese female and its functional characterization. A beta-variant hemoglobin, first misjudged as a marked elevation of Hb A1, was found in a 68-year-old Japanese female with diabetes mellitus. This hemoglobin was isolated by Bio-Rex 70 chromatography combined with chromatofocusing, and was found to be Hb hope, beta 136(H14)Gly Asp, by classical and high performance liquid chromatographic peptide mapping techniques. Intrinsic oxygen affinity of this hemoglobin was approximately one-third as compared with that of Hb A0. This property was still observed in the constituent beta subunits isolated. Effects of such allosteric effectors as H (at a fixed concentration of Cl-), anion (Cl-), 2,3-diphosphoglycerate and carbon dioxide were more or less depressed. Among others, a marked reduction in the carbamate effect should be noted in a structural interpretation of the functional modifications. Subunit cooperativity, on the contrary, was not different from that in Hb A0 (n = 2.8-2.9). Explanation of these altered functions were attempted on the basis of the altered structure. The reduced stability of Hb hope is also described.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
8/11. Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.A 45-yr-old muscular nonobese white man who had a 9-yr history of syncopal episodes was studied on several occasions between April 1979 and August 1984. fasting glucose concentrations ranged between 74-115 mg/dl, and those of insulin ranged between 14-64 microU/ml. Reactive hypoglycemia 3-4 h after ingestion of glucose occurred in the first 2 yr. Glucose tolerance was impaired in 1979, from February 1982 through September 1983, and again in August 1984. The maximum plasma insulin response to glucose ranged between 475-1630 microU/ml. When studied in November 1982, insulin (0.1 U/kg) caused a fall in blood glucose concentration of only 25% (normal, greater than 50%), and maximal glucose utilization during the euglycemic hyperinsulinemic clamp was 7.5 mg/kg . min (normal, greater than 12 mg/kg . min). plasma counterregulatory hormone concentrations were normal, and antibodies to insulin and the insulin receptor were absent. Binding of exogenous insulin to the patient's cellular receptors (monocytes, red blood cells, and skin fibroblasts) was normal. Insulin was purified from plasma by immunoaffinity and molecular sieve chromatography and was found to elute later than human insulin on reversed phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to and stimulate glucose metabolism in isolated rat adipocytes. The abnormal insulin was identified in two of three sons and a sister, but not in the mother, brother, or niece. Sensitivity to insulin was normal in the two sons who had abnormal insulin. These results suggest that in this family the abnormal insulin was due to a biosynthetic defect, inherited as an autosomal dominant trait. The hyperinsulinemia was not associated with diabetes in family members who had no insulin resistance.- - - - - - - - - - ranking = 2keywords = chromatography (Clic here for more details about this article) |
9/11. Hb Marseille [alpha 2 beta 2 N methionyl-2 (NA2) HisPro]: a new beta chain variant having an extended N-terminus. A new abnormal hemoglobin was found in a diabetic Maltese woman by citrate agar electrophoresis. This variant was undetectable by isoelectric focusing. No hematological abnormalities were observed. The structural analysis included isolation of the abnormal beta chain, high pressure liquid chromatography of the corresponding tryptic peptides and then microsequencing of the abnormal T1. These procedures revealed a double abnormality: the presence of a methionyl residue extending the NH2 terminus and a histidine to proline substitution in position NA2.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
10/11. Hemoglobin Old Dominion/Burton-upon-Trent, beta 143 (H21) His-->Tyr, codon 143 CAC-->TAC--a variant with altered oxygen affinity that compromises measurement of glycated hemoglobin in diabetes mellitus: structure, function, and dna sequence.OBJECTIVE: To determine the nature and characteristics of a unique hemoglobin variant that causes a spurious increase in glycated hemoglobin (HbA1c). MATERIAL AND methods: Blood specimens from four unrelated persons with this hemoglobin variant were examined by conventional laboratory methods, including electrophoresis, high-performance ion-exchange chromatography, and isoelectric focusing; by amino acid sequence analysis, polymerase chain reaction-based dna sequence analysis, and electrospray ionization mass spectrometry, to establish the molecular structure; and by studies of oxygen affinity under varied conditions, to define the functional characteristics of the hemoglobin variant. RESULTS: The unique hemoglobin variant observed in these four cases is due to the mutation CAC-->TAC, at beta-globin gene codon 143, corresponding to beta 143 (H21) His-->Tyr. This amino acid substitution affects an important 2,3-diphosphoglycerate binding site and slightly increases the oxygen affinity of the hemoglobin variant. CONCLUSION: A hitherto unrecognized hemoglobin variant, encountered in four unrelated persons of Irish or Scots-Irish ancestry, hemoglobin Old Dominion/Burton-upon-Trent, beta 143 (H21) His-->Tyr, has now been characterized at the molecular, structural, and functional levels. Although it is associated with a slight increase in oxygen affinity, it is without hematologic effect, and its only clinical significance is that it coelutes with HbA1c on ion-exchange chromatography and thereby causes a spurious increase in HbA1c and compromises the use of this analyte to monitor the treatment of diabetes mellitus.- - - - - - - - - - ranking = 2keywords = chromatography (Clic here for more details about this article) |
| | Next -> |