Rainer W. Lipp

Silent haemoglobin variants and determination of HbA1c with the HPLC Bio-Rad Variant II

Aims: To evaluate the determination of HbA1c with an automated high performance liquid chromatography (HPLC) method in patients with clinically silent haemoglobin variants. Methods: HbA1c values were determined with the ion exchange HPL Bio-Rad Variant II using the high resolution β thalassaemia programme in patients with silent haemoglobin variants, namely: Hb Graz, Hb Sherwood Forest, Hb O Padova, and Hb D. Results: All of these haemoglobin variants caused additional peaks in the chromatograms. No clinically useful HbA1c results were produced for patients with Hb Graz and Hb Sherwood Forest, the results for the patient with Hb D were too low, but the results for patients with Hb O Padova were acceptable. Conclusions: The development of this automated HPLC method modification with high resolution mode aids the identification of interference caused by the described clinically silent haemoglobin variants in HbA1c determination.

Insights into epiploic appendagitis

Epiploic appendagitis is a rare cause of abdominal pain. Diagnosis of epiploic appendagitis, although infrequent, is easily made with CT or ultrasonography in experienced hands. As reported in the literature, most patients with primary epiploic appendagitis are treated conservatively without surgery, with or without anti-inflammatory drugs. A small number of patients are treated with antibiotics and some patients require surgical intervention to ensure therapeutic success. Symptoms of primary epiploic appendagitis usually resolve with or without treatment within a few days. A correct diagnosis of epiploic appendagitis with imaging procedures enables conservative and successful outpatient management of the condition and avoids unnecessary surgical intervention and associated additional health-care costs. Gastroenterologists and all medical personnel should be aware of this rare disease, which mimics many other intra-abdominal acute and subacute conditions, such as diverticulitis, cholecystitis and appendicitis. This article reviews epiploic appendagitis and includes discussion of clinical findings, pathophysiology, diagnosis and therapeutic possibilities.

99mTc-apcitide scintigraphy in patients with clinically suspected deep venous thrombosis and pulmonary embolism

AimDetection of acute deep venous thrombosis (DVT) in patients presenting with clinical symptoms suggesting DVT and pulmonary embolism (PE) with 99mTc-apcitide, a synthetic polypeptide, binding to glycoprotein IIb/IIIa receptors expressed on activated platelets is the objective of the study.Materials and methodsNineteen patients (11 males, eight females) received within 24h after admission to the hospital a mean of 841MBq (range 667 to 1,080) 99mTc-apcitide i.v. followed by planar recordings 10, 60, and 120min after injection. Images were compared to the results of compression ultrasonography and/or phlebography. Patients with clinically suspected PE underwent spiral computed tomography or lung perfusion scans.Results99mTc-apcitide scintigraphy showed acute clot formation in 14 out of 16 patients where the other imaging modalities suggested DVT. Positive scintigraphic results were seen up to 17days after the onset of clinical symptoms. In three out of three patients without any proof of DVT, 99mTc-apcitide scintigraphy was truly negative. Glycoprotein receptor imaging showed only one segmental PE in six patients with imaging-proven subsegmental (N = 3) or segmental PE (N = 3).Conclusion99mTc-apcitide scintigraphy may be an easy and promising tool for the detection of acute clot formation in patients with DVT up to 17days after the onset of clinical symptoms with a sensitivity of 87% and a specificity of 100%. However, it failed to demonstrate PE in 83% of examined patients with proven PE.

Haemoglobin O Padova and falsely low haemoglobin A1c in a patient with type I diabetes.

Glycated haemoglobin (HbA1c) measured by high performance liquid chromatography (HPLC) in a 20 year old female with insulin dependent diabetes mellitus was consistently within the normal range although her daily blood glucose values were > 11.1 mmol/l. HbA1c measured by immunoagglutination and fructosamine was elevated and correlated with the patients blood glucose values. The HPLC chromatogram showed an additional peak at HbA0. Electrophoresis of haemoglobin on citrate agar gel revealed an abnormal haemoglobin anodal of HbS. Cellulose acetate electrophoresis and isoelectric focusing demonstrated an additional haemoglobin migrating close to HbA2. Amino acid analysis and DNA sequencing revealed an alpha 30 (B11) Glu-->Lys replacement, that is, haemoglobin O Padova. Investigations of two family members without diabetes revealed the same rare haemoglobin variant. This case showed that this silent haemoglobin mutation caused an additional peak and falsely low HbA1c values when measured by HPLC, the gold standard for this evaluation.

Hemoglobin variants recently detected in Austria

Measurement of glycated hemoglobin (HbA1c) is used for routine management of diabetic patients. Glucose linkage to HbA1c reflects mean blood glucose levels during the last 3 months before examination. Various methods for HbA1c determination show abnormal values with hemoglobin variants. In some diabetic patients excessively high HbA1c values with high-performance liquid chromatography (HPLC) led to the detection of Hb Graz. In addition to Hb Graz, other silent hemoglobin variants have been found in Austria. Here we review Hb Graz, Hb Sherwood Forest, and Hb Okayama detected while using HPLC for the measurement of HbA1c in diabetic patients.

Effect of steroid treatment on the migration behaviour of neutrophils in patients with early rheumatoid arthritis

Abstract The influence of methylprednisolone on the migratory characteristics of neutrophil granulocytes was investigated in 10 patients with early rheumatoid arthritis (RA) and compared to 12 controls. The migration of neutrophils was measured with a whole-blood membrane filter assay with and without stimulation by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP). Total migration index (TMI), distribution characteristics (DC) and the product of TMI and DC (neutrophil migratory activity; NMA) served to characterize the migratory behaviour of neutrophils. The data demonstrated an increased polymorphonuclear leucocyte (PMN) migration in patients with early RA, indicating a bystander role of PMNs in inflammatory joint injury. Treatment with methylprednisolone reduced significantly the penetration depth (DC) of neutrophils, but did not influence the number of migrating cells (TMI). The unstimulated NMA was significantly reduced due to the marked DC reduction, whereas steroids did not influence the stimulated NMA of neutrophils. A significant reduction in PMN penetration depth was demonstrated only after a steroid therapy of at least 10 days, suggesting that a longer period of steroid therapy is necessary to provide effective inflammatory control.

Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

Objective: Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of 99mTc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with 177Lu-DOTATATE used for PRRT. Methods: 8 patients (4 women, 4 men, age range 46–76 years) with histologically proven NETs, who showed high SR loads by 99mTc-EDDA/HYNIC-TOC scintigraphy, were treated with 177Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. Results: All patients demonstrated 177Lu-DOTATATE accumulation in all lesions previously detected by 99mTc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. Conclusions: SPECT-CT after 177Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using 99mTc-EDDA/HYNIC-TOC. This could reflect the broader affinity of 177Lu-DOTATATE for SRs compared with 99mTc-EDDA/HYNIC-TOC.

Primary Epiploic Appendagitis

42-year-old female patient presented with vomiting, bloat-ing, diarrhea, and a dull constant abdominal pain at admis-sion. She reported a history of recurrent complaints and intermit-tent febrile temperature up to 38.5°C. Her symptoms includedtenderness in the right upper abdominal quadrant, postprandialfullness, epigastric discomfort, early satiety, and weight loss of5 kg during the preceding 4 months. Gastrointestinal examina-tions including abdominal ultrasound, colonoscopy with ter-minal ileum intubation, gastroscopy, and lactose-intolerancetest provided no explanation for her symptoms. At admission,abnormal laboratory parameters included C-reactive protein 33mg/L (normal, 5 mg/L) and 83% (normal, 42%–75%) neutro-phil leukocytes. Routine laboratory parameters including allother parameters of white blood count, erythrocyte sedimenta-tion rate, and liver and pancreas enzymes were within normallimits. Abdominal computed tomography (CT) with intrave-nous contrast medium demonstrated an oval lesion, maximumdiameter 2.7 cm, with fat attenuation, located close below theliver and adjacent to the ascending colon (Figures

Metabolic Pattern of Asymptomatic Hip-Prosthesis by 18F-FDG-Positron-Emission-Tomography.

Background: Joint replacement is a procedure with a major impact on the quality of life of patients with joint degenerative disease or traumatic injuries. However, some patients develop symptoms after the intervention caused by mechanical loosening or infection. Metabolic imaging by 18F-FDG-PET investigated in these patients isoften hampered by low specificity for diagnosis of possible septic vs. mechanical loosening. The reason for this shortcoming is to our opinion the unawareness of physiological remodeling processes that could be seen in asymptomatic patients. Objectives: In order to overcome this drawback, we aimed to find out the physiological metabolic functional pattern in asymptomatic patients with implanted hip prosthesis Patients and Methods: Twelve patients (6 males, 6 females); mean age 73 ± 7 (range 58 - 91) years were prospectively enrolled in the study. The patients were admitted to our department for oncological referral with implanted hip prostheses. All patients explained no symptoms with regard to their implanted prosthesis. The attenuation corrected images were used for analysis. Results: Fourteen hip prostheses in 12 patients were visually analyzed. Seven out of 14 prostheses among 12 patients showed focal periprosthetic enhanced metabolism, two of which showed two sites of enhanced uptake; whereas, the remaining five prostheses showed singular hypermetabolic areas within the periprosthetic site. The remaining seven prostheses in the other five patients showed no periprosthetic-enhanced uptake. Conclusion: Of the asymptomatic patients investigated, 58% showed focal enhanced periprosthetic glucose metabolism. This finding should be taken into consideration as a more probable unspecific metabolic pattern for correct interpretation of 18F-FDG-PET studies in patients with suspected septic loosening of the hip prosthesis.

Primary epiploic appendagitis and fructose malabsorption.

Primary epiploic appendagitis (PEA) is a rare cause of abdominal acute or subacute complaints. Diagnosis of PEA is made when computed tomography (CT) reveals a characteristic lesion. We report on contrast-enhanced CT images of a patient with PEA and regression of inflammation and the reduction in size of the inflamed appendage over the time period of 4 months. Patients with PEA usually recover without medication or surgical treatment within a few weeks. However, due to continuing bloating and irregular bowel movements we investigated carbohydrate malabsorption and diagnosed a fructose malabsorption. Bloating and irregular bowel movements in this patient with PEA were correlated to carbohydrate malabsorption and were treated successfully with a diet free of culprit carbohydrates.