Jens Oluf Pedersen

Long-term supplementation with n-3 fatty acids, II: Effect on neutrophil and monocyte chemotaxis.

The effect of a daily supplement with 4 g of n-3 polyunsaturated fatty acids (PUFA) for 9 months to 24 healthy volunteers on neutrophil and monocyte chemotaxis was studied using the under-agarose technique. Autologous serum and n-formyl-methionyl-leucyl-phenylalanine were used as chemoattractants. The effect after 9 months of supplementation with n-3 PUFA was also compared to results after short-term supplementation with n-3 PUFA for 6 weeks. Monocyte chemotaxis was reduced after 9 months of supplementation with n-3 PUFA to the same extent as after 6 weeks supplement. Neutrophil-directed migration towards chemoattractants was reduced after 9 months on fish oil, and this decrease was significantly greater than the decrease obtained after 6 weeks of supplementation. The spontaneous migration of neutrophils was significantly attenuated after 9 months compared to baseline and to 6 weeks. These findings lend support to a role for n-3 PUFA in the management of chronic inflammatory and atherosclerotic vascular diseases.

Cancer risk in patients with monoclonal gammopathy of undetermined significance

To assess the cancer risk of monoclonal gammopathy of undetermined significance (MGUS) we identified 1229 cases of MGUS in the period 1978 to 1993. Data on cancer occurrence in the MGUS cohort were obtained from the Danish Cancer Registry. The expected numbers of cancer cases were calculated from age‐, sex‐, county‐, and period‐specific cancer incidence rates. In the MGUS cohort 64 new cancers with a known association with M‐components were diagnosed versus 5.0 expected giving a standardized incidence ratio (SIR) of 12.9 (95% confidence interval, 9.9–16.5). The relative risks of developing multiple myeloma (SIR 34.3), Waldenströms macroglobulinemia (SIR 63.8), and non‐Hodgkins lymphoma (SIR 5.9) were significantly increased and independent of time passed from detection of the M‐component. The relative risk of chronic lymphocytic leukemia was not significantly increased, SIR 2.7 (0.5‐7.7). Among cancer sites without known association with M‐components 141 cases were observed versus 94.6 expected giving a SIR of 1.5 (1.3‐1.8). This enhanced risk was seen for several non‐hematological cancer sites but for most cancer sites the risk was dependent on time passed from detection of the M‐component, indicating a bias rather than a causal role of MGUS. Am. J. Hematol. 63:1–6, 2000.

On the kinetics of complement activation, leucopenia and granulocyte-elastase release induced by haemodialysis.

In order to elucidate the kinetics of haemodialysis-induced activation of complement, leucopenia and release of granulocyte-elastase, 10 patients (three females and seven males; mean age 47.8 years) were extensively studied during a 4 h haemodialysis treatment and for the following 24 h, and further compared with a healthy control group. Prior to dialysis patients had normal leucocyte count, plasma elastase bound to alpha 1-proteinase inhibitor (E-alpha 1P1) and total haemolytic complement, whereas plasma C3d was higher and plasma C5a lower than in controls. Haemodialysis induced initial leucopenia and subsequent rebound phenomenon lasting 24 h post treatment. These alterations were due to almost selective changes in neutrophile count as monocyte and lymphocyte counts, apart from decrease in the first 30 min, were unchanged. Total haemolytic complement decreased initially during dialysis and rose at the end. Generation of C5a within the dialyser was evident by demonstration of high levels of this anaphylatoxin in dialyser effluent plasma; maximal values observed coincided with the nadir of leukopenia. Plasma C3d and E-alpha 1P1 both progressively rose during dialysis. After termination of extracorporeal circulation the disappearance rates (T/2) were approximately 6 h and 2.5 h respectively. Haemodialysis thus induces changes in the complement and leucocyte system resembling an acute inflammation, which out-lasts the treatment period.

Leukopenia and Release of Granulocyte Elastase: Interlinked Membrane-Dependent Events during Hemodialysis

In order to investigate the effect of dialyzer membrane material on hemodialysis-induced leukopenia and release of granulocyte elastase, 12 patients were studied during two successive dialyses using membranes based on regenerated cellulose (RC) and cellulose acetate (CA). RC membranes induced greater and more prolonged leukopenia than did CA membranes. Release of granulocyte elastase, assessed as changes in plasma levels of elastase in complex with α1-proteinase inhibitor (E-α1-PI), increased with both membranes, but significantly more with RC membranes. The demonstrated liberation of granulocyte elastase could contribute to the deterioration of pulmonary function reported during hemodialysis. Furthermore, we suggest that measurement of E-α1-PI may be used to evaluate biocompatibility of dialyzer membranes.

Real-time scanning and image analysis: A fast method for the determination of neutrophil orientation under agarose

We describe a newly developed method for fast determination of neutrophil chemotaxis and orientation in concentration gradients of chemotactic factors. The system implements video-based real-time scanning and image analysis of neutrophil migration under agarose, using an interactive easy-to-use computer program. Two methods for determining cell orientation are presented. No statistically significant difference between the methods was found. The analysis program distinguishes between chemokinetic and chemotactic behaviour of the cells (P less than 0.01).

Activation of Complement, Generation of C5a, Leukopenia and Hypoxemia: Interlinked Membrane-Dependent Events during Hemodialysis

Differences in biocompatibility of various hemodialysis membranes cause different degrees of complement activation, leukopenia, and hypoxemia during hemodialysis. In order to further clarify the compl

Complement and leukocytes during cardiopulmonary bypass: Effects on plasma cad and C5a, leukocyte countr Release of granulocyte elastase and granulocyte chemotaxis

In an effort to further elucidate the complex changes in the complement-leukocyte system during cardiopulmonary bypass (CPB), plasma levels of C3d, C5a, and granulocyte elastase bound to alpha1-proteinase inhibitor (E-alpha1 PI) were followed prior to, during, and after CPB. Leukocyte and differential cell counts and granulocyte migration were also determined. Complement activation was documented during CPB by an increase in plasma C3d corrected for hemodilution. Significant amounts of C5a were not revealed. Cell counts decreased during CPB but, if corrected for hemodilution, remained unchanged apart from a slight decrease in lymphocyte count after 60 minutes. Eighteen hours after CPB, neutrocytosis and lymphopenia occurred. Plasma E-alpha1 PI increased during CPB, reflecting release of granulocyte lysosomal enzymes. Granulocyte migration was transitorily depressed during CPB, and it was shown that this was due to the appearance of an intrinsic cellular defect. CPB is associated with acute changes in cells and plasma, resembling an acute whole-body inflammatory response, with transitory impairment of granulocyte migration. The clinical significance of these observations remains to be determined.

The ability of uremic serum to induce neutrophil chemotaxis in relation to hemodialysis.

The ability of serum to attract normal neutrophil granulocytes was investigated in 11 uremic patients before and after hemodialysis using a modified assay system for granulocyte migration under agarose. The chemotactic responses towards serum from the uremic patients were significantly decreased (p less than 0.01) prior to hemodialysis compared to control serum from a healthy individual. Hemodialysis acutely normalized the depressed chemotactic responses. It is concluded that hemodialysis improves the ability of uremic serum to attract neutrophils, and it is suggested that this improvement might be due to removal of granulocyte inhibitory factors from the sera.

Biocompatibility of a new polycarbonate dialysis membrane.

The present report summarizes our experience with a new polycarbonate (PC)-based dialysis membrane (Gambro Lundia PRO-5) compared with a cuprophan (CP)-based membrane (Gambro Lundia 10-5N). Platelet count decreased during dialysis with CP, but was unchanged with PC membranes. Platelet injury, reflected by decreased platelet aggregation and increase in plasma beta-thromboglobulin, occurred equally with both membranes. Complement activation (C3d and C5a), leukopenia and release of granulocyte-derived elastase was more extensive with CP than with PC membranes. The new membrane represents an improvement of biocompatibility with respect to the complement-leukocyte system, whereas the effect on platelets resembles the injury caused by CP membranes.

Serum trypsin-like immunoreactivity and steatorrhea

To The Editor: Steinberg (1) and Andriulli and Masoero (2) discussed the potential use of serum trypsin-like immunoreactivity (serum TLI) in differentiating pancreatic from nonpancreatic steatorrhea. Jacobson et al (3) found that all 14 patients with pancreatic steatorrhea had serum TLI below both control subjects and 17 patients with nonpancreatic steatorrhea with no overlap of values. Using the definitions given by Galen and Gambino (4), this indicates that using a serum TLI below reference range as a positive test for pancreatic steatorrhea has a 100% sensitivity and specificity in steatorrhea patients. Unfortunately, false-negative results do occur in pancreatic steatorrhea: Fasting serum TLI (RIAgnost| trypsin, Behringwerke AG, Marburg, FRG) was measured in 29 patients consecutively examined with fecal fat (5) excretion for three days on a diet of 100 g of fat per day due to clinical suspicion of steatorrhea. The exocrine pancreatic function was evaluated by the postprandial concentration of amylase, lipase, and TLI in duodenal aspirate (Lundh test) (6, 7). No patient had serum creatinine above 125 ~mol/liter (1.1 mg/liter) excluding renal insufficiency (3) as a cause of elevated serum TLI. Twenty-five patients had confirmed steatorrhea (>7 g of fecal fat excretion per day) with fetal fat excretion ranging from 10 to 70 g per day. Nine patients had nonpancreatic steatorrhea (due to small intestinal diseases) and 16 patients had pancreatic steatorrhea (due to chronic pancreatitis). The four patients without steatorrhea and the nine with nonpancreatic steatorrhea all had serum TLI in the reference range (130-660 ~g Behringwerke standard per liter). Four patients with pancreatic steatorrhea also had serum TLI in the reference range, and these patients all had an acute exacerbation of their disease during or up to four weeks before this investigation. Two other patients had acute excerbations of chronic pancreatitis but no detectable serum or duodenal TLI. Serum TLI was below reference range or undetectable in the 10 other patients with pancreatic steatorrhea. These results give a sensitivity of 75%, a specificity of 100% (no false positive), a predictive value of a negative test result of 69%, a predictive value of a positive test result of 100%, and an efficiency of 84% when serum TLI below reference range is taken as a positive test of pancreatic steatorrhea in patients with steatorrhea. Other investigators (8-11) have found serum TLI in or even above the reference range in chronic pancreatitis patients with steatorrhea: In patients investigated in a quiet disease phase, Andriulli et al (8) found four of 24 patients and Enslev et al (9) found seven of 17 patients. In two investigation s without information of disease state, three of nine patients (10) and eight of 52 patients (11) had serum TLI in the reference range. We conclude that serum TLI below reference range in steatorrhea patients seems specific for pancreatic steatorrhea, but a serum TLI in the reference range does not exclude a pancreatic origin of steatorrhea. JENS MgILLER-PETERSEN, MD Department of Internal Medicine H JENS O. PEDERSEN, MD Department of Internal Medicine I Aalborg Hospital, Aalborg, Denmark