Ivan Gornik

Fucosylation of IgG heavy chains is increased in rheumatoid arthritis

OBJECTIVES Glycosylation of IgG was suggested to be important in the etiology of rheumatoid diseases. Most studies addressed the amount of galactose, but recently we showed that fucose is highly increased in the juvenile chronic arthritis. The objective of this study was to determine fucosylation of IgG heavy chains in patients with rheumatoid arthritis (RA). DESIGN AND METHODS IgG was purified from sera of 29 RA patients and 17 matching controls using ammonium sulfate precipitation and ion exchange. Heavy chains were separated by denaturing polyacrylamide gel electrophoresis and their fucosylation analysed using fucose-specific UEA I lectin. RESULTS Fucose was found to be approximately 40% increased in RA patients with very high statistical significance (p = 0.00095). CONCLUSIONS Fucose on IgG heavy chains is significantly increased in patients with rheumatoid arthritis.

A prospective observational study of the relationship of critical illness associated hyperglycaemia in medical ICU patients and subsequent development of type 2 diabetes

IntroductionCritical illness is commonly complicated by hyperglycaemia caused by mediators of stress and inflammation. Severity of disease is the main risk factor for development of hyperglycaemia, but not all severely ill develop hyperglycemia and some do even in mild disease. We hypothesised that acute disease only exposes a latent disturbance of glucose metabolism which puts those patients at higher risk for developing diabetes.MethodsMedical patients with no history of impaired glucose metabolism or other endocrine disorder admitted to an intensive care unit between July 1998 and June 2004 were considered for inclusion. Glucose was measured at least two times a day, and patients were divided into the hyperglycaemia group (glucose ≥7.8 mmol/l) and normoglycaemia group. An oral glucose tolerance test was performed within six weeks after discharge to disclose patients with unknown diabetes or pre-diabetes who were excluded. Patients treated with corticosteroids and those terminally ill were also excluded from the follow-up which lasted for a minimum of five years with annual oral glucose tolerance tests.ResultsA five-year follow-up was completed for 398 patients in the normoglycaemia group, of which 14 (3.5%) developed type 2 diabetes. In the hyperglycaemia group 193 patients finished follow-up and 33 (17.1%) developed type 2 diabetes. The relative risk for type 2 diabetes during five years after the acute illness was 5.6 (95% confidence interval (CI) 3.1 to 10.2).ConclusionsPatients with hyperglycaemia during acute illness who are not diagnosed with diabetes before or during the hospitalization should be considered a population at increased risk for developing diabetes. They should, therefore, be followed-up, in order to be timely diagnosed and treated.

Fucosylation and galactosylation of IgG heavy chains differ between acute and remission phases of juvenile chronic arthritis

Abstract Oligosaccharide structures are attached to nearly all membrane and serum proteins, and their composition changes significantly in many diseases. We have analysed glycosylation of IgG heavy chains in 34 patients with juvenile chronic arthritis and 13 control individuals. IgG was purified from 0.7 ml of serum, separated by electrophoresis and transferred on to polyvinylidene difluoride (PVDF) membrane. Ricinus communis agglutinin (RCA I) and Bandeirea simplicifolia (BSA II) and Ulex europaeus (UEA I) lectins were used to measure galactose, N-acetylglucosamine and fucose, respectively. While there was no significant difference in average levels of galactose and N-acetylglucosamine, patients with juvenile chronic arthritis had 2.4 times more fucose attached to IgG heavy chains than control individuals. A different picture emerged when patients were divided into those with acute disease and those in remission. Patients in whom juvenile chronic arthritis was currently active had significantly lower levels of galactose than those in remission, in whom galactose levels were comparable to the control group. Fucose levels in both groups of patients were significantly higher than in the control group. These results show that whereas de-galactosylation is a good test to detect and measure the activity of juvenile chronic arthritis, increased fucosylation is a much more reliable measure for diagnosis of the disease itself.

The identification of war victims by reverse paternity is associated with significant risks of false inclusion

Abstract. Since February 2001 the process of DNA identification of war victims in Croatia relies on the database of over 3,000 9-locus (D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317 and D7S820) STR genotypes of relatives of missing persons. Instead of a targeted approach to DNA typing, the genotype of each skeletal remains analysed is compared to all genotypes in the database to identify potential parents and children. Although this approach has significantly increased the pace of identification by DNA typing, non-targeted matching in a database containing several thousand genotypes considerably decreases the significance of inclusion, especially when identification is based on reverse paternity analysis. To support this statistical prediction we present 3 cases of 10 STR loci matches and 1 case of 11 STR loci matches between a child, childs mother and skeletal remains that did not originate from a father of that child.

Hyperglycemia in sepsis is a risk factor for development of type II diabetes

BACKGROUND Hyperglycemia is frequent in sepsis, even in patients without diabetes or impaired glucose metabolism. It is a consequence of inflammatory response and stress, so its occurrence is related to severity of illness. However, not all severely ill develop hyperglycemia and some do even in mild disease. We hypothesized the existence of latent disturbance of glucose metabolism that contributes to development of hyperglycemia and that those patients might have increased risk for diabetes. METHODS Patients admitted with sepsis and no history of impaired glucose metabolism were included and divided in the hyperglycemia group (glucose >or=7.8 mmol/L) and normoglycemia group. Severity of sepsis was assessed. Surviving patients without diabetes at discharge were followed-up for 5 years to investigate risk for development of diabetes. RESULTS Hyperglycemia was related to severity of sepsis. Follow-up was finished for 55 patients with hyperglycemia, of which 8 (15.7%) developed diabetes, and 118 patients with normoglycemia, of which 5 (4.2%) developed diabetes (P = .002). Relative risk for developing type 2 diabetes was 4.29 (95% CI, 1.35-13.64). CONCLUSION Patients with hyperglycemia in sepsis who are not diagnosed with diabetes before or during the hospitalization should be considered a population at increased risk for developing diabetes.

Free serum DNA is an early predictor of severity in acute pancreatitis

OBJECTIVES Cell-free DNA has been investigated as a diagnostic marker in many diseases, including acute conditions. Our hypothesis was that in acute pancreatitis free serum DNA correlates with the extent of pancreatic necrosis and that it may be an early marker of severity. DESIGN AND METHODS Free DNA was measured in sera from 30 patients with acute pancreatitis at admission, on the first, fourth and seventh day following admission. RESULTS On the first day following admission patients who would develop severe pancreatitis had significantly higher serum DNA levels than those with mild disease (median 0.271 ng/microL vs. 0.059 ng/microL respectively; P<0.001). This parameter showed very good characteristics as a potential severity predictor (area under ROC curve 0.97). Free serum DNA was in correlation with the extent of pancreatic necrosis. CONCLUSIONS Free serum DNA correlates with the extent of pancreatic necrosis and is a potential early marker of severe acute pancreatitis.

Change in transferrin sialylation is a potential prognostic marker for severity of acute pancreatitis.

OBJECTIVES Early prediction of severe acute pancreatitis is one of the problems in clinical practice. Since many diseases are associated with alteration in glycosylation, in this work we studied sialylation of transferrin and serum proteins in acute pancreatitis. DESIGN AND METHODS Sialylation was analyzed during first eight days of hospitalization of 30 patients and compared to 28 healthy controls. Transferrin sialylation was measured using enzyme linked lectin assay, while sialic acid on proteins was measured using resorcinol method. RESULTS Both analyzed parameters changed during studied period. The change in transferrin sialylation between Day1 and Day2 of hospitalization was shown to be an early prognostic marker of acute pancreatitis, with better sensitivity (88.9%) and specificity (90.5%) than other markers tested. CONCLUSIONS Sialylation of transferrin and total serum proteins reflects the intensity of inflammatory response during acute pancreatitis and could be used as prognostic parameter for disease severity.

Hematologic malignancies in the medical intensive care unit – Outcomes and prognostic factors

Abstract Objectives To analyze clinical characteristics, treatment, outcomes of critically ill patients with hematologic malignancies (HM) admitted to the medical intensive care unit (ICU) and to identify predictors of adverse outcome. Methods We analyzed prospectively 170 patients. Data included: demographic characteristics, hematologic diagnosis, reasons for ICU admission, transplant status, the presence of neutropenia, acute physiology and chronic health evaluation-II and sequential organ failure assessment scores, and level of organ support. Predictors of ICU mortality were evaluated using univariate and multivariate analysis. Results In total, 73% of patients had high-grade malignancy, 47.6% received intensive chemotherapy before admission, and 30% underwent hematologic stem cell transplantation procedure. In total, 116 (68.2%) of patients were mechanically ventilated; 88 (51.8%) required invasive mechanical ventilation (MV). Non-invasive ventilation started in 28 (16.5%) patients and was successful in 11 (6.5%). The ICU mortality rate was 53.5%, and the mortality of MV patients was 75.9%. Need for vasopressors at admission and MV were identified as independent predictors of fatal outcome. Conclusion The ICU mortality of critically ill patients with HM is high, particularly in the group of MV. Need for vasopressors at admission and MV were independent predictors of ICU mortality. Majority of patients required invasive MV due to severe respiratory failure and non-invasive MV was sufficient only in small number of cases with favorable outcome.

Correction to: Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes

The authors regret that Nish Chaturvedi’s name was spelt incorrectly in the author list. The details given in this correction are correct.