Introduction: Biclonal gammopathies represent about 5% of clonal gammopathies. We describe the clinical and laboratory features of biclonal gammopathies identified in a French university hospital.

PURPOSE:Monoclonal gammopathy are common in the general population. We describe biological features and etiology of monoclonal gammopathy diagnosed during more than a ten year period in the Internal Medicine Department of Rennes University Hospital and in all the medical departments of General Hospital of Blois.METHODS:Patients were identified by immunofixation registry of Biochemistry Laboratories in both hospital (from 1990 in Rennes and from 1980 in Blois).RESULTS:Internal Medicine Department of Rennes University Hospital: 1051 monoclonal gammapathies were identified: 514 men and 537 women. Median age was 71. Isotypes repartition was: IgG 42.8% (450 cases), IgM 31.9% (335), IgA 8.9% (94) biclonal gammopathy 9.8% (103). Sixty-nine monoclonal light chains (6.6%) were identified. Median concentration of monoclonal protein was 14 g/l (1.8-104.4). All department of General Hospital of Blois: 1282 monoclonal gammapathies were identified: 700 men and 582 women. Median age was 79. Isotypes repartition was: IgG 59.7% (765 cases), IgM 27.5% (329), IgA 11.8% (151). Thirty-four monoclonal light chains (2.7%) were identified. Median concentration of monoclonal protein was 5.6 g/l (0.5-96.6). Most frequent diagnosis were: monoclonal gammopathy of undetermined significance or MGUS (77.6% in Blois and 64.1% in Rennes), multiple myeloma (11.9% and 12.7%), Waldenström's macroglobulinemia (4.4% and 8.7%).CONCLUSION:Monoclonal gammopathy are common in clinical practice. MGUS account for more than 60% of monoclonal gammopathy. Given their frequency, diagnostic and follow-up strategies must be costless and simple.

Purpose. - Monoclonal gammopathy are common in the general population. We describe biological features and etiology of monoclonal gammopathy diagnosed during more than a ten year period in the Internal Medicine Department of Rennes University Hospital and in all the medical departments of General Hospital of Blois.Methods. - Patients were identified by immunofixation registry of Biochemistry Laboratories in both hospital (from 1990 in Rennes and from 1980 in Blois).Results. - Internal Medicine Department of Rennes University Hospital.- 1051 monoclonal garnmapathies were identified: 514 men and 537 women. Median age was 71. lsotypes repartition was: IgG 42.8 % (450 cases), IgM 31.9 % (335), IgA 8.9 % (94) biclonal gammopathy 9.8 % (103). Sixty-nine monoclonal light chains (6.6 %) were identified. Median concentration of monoclonal protein was 14 g/l (1.8-104.4). All department of General Hospital of Blois: 1282 monoclonal gammapathies were identified: 700 men and 582 women. Median age was 79. Isotypes repartition was: IgG 59.7 % (765 cases), IgM 27.5 % (329), IgA 11.8 % (15 1). Thirty-four monoclonal light chains (2.7 %) were identified. Median concentration of monoclonal protein was 5.6 g/1 (0.5-96.6). Most frequent diagnosis were: monoclonal gammopathy of undetermined significance or MGUS (77.6 % in Blois and 64.1 % in Rennes), multiple myeloma (11.9 % and 12.7 %), Waldenstrom's macroglobulinemia (4.4 % and 8.7 %).Conclusion. - Monoclonal gammopathy are common in clinical practice. MGUS account for more than 60 % of monoclonal gammopathy. Given their frequency, diagnostic and follow-up strategies must be costless and simple. (C) 2007 Elsevier Masson SAS. Tous droits reserves.

SummaryThe non‐random association of Gaucher disease with polyclonal and monoclonal gammopathy has been known since 1950. The effect of treatment on monoclonal gammopathy is not well documented. We report on the long‐term evolution of a biclonal gammopathy in a patient with type I Gaucher disease who was treated with splenectomy and enzyme replacement therapy. A 44‐year‐old man presented with hepatomegaly and massive splenomegaly. Bone marrow aspirate contained typical Gaucher cells and β‐glucosidase was low in peripheral blood leukocytes. Mutations N370S and R120W were detected. Serum protein electrophoresis disclosed two spikes in gammaglobulins. Immunofixation identified two monoclonal components: IgG kappa and IgA kappa. Gammaglobulin concentration was 31.6 g/L. A splenectomy was performed on September 2003 because of massive splenomegaly (9500 g). Two months after the splenectomy, gammaglobulin concentration was 25.2 g/L. Enzyme replacement therapy (Cerezyme 45 UI/kg every two weeks) was prescribed from April 2004 because of significant hepatomegaly and cholestasis. In April 2007 (3 years after the beginning of treatment), serum electrophoresis showed the persistence of two spikes with gammaglobulin concentration at 20.5 g/L. Simultaneously, chitotriosidase activity decreased from 6181 to 2877 nkat/L. Our observation and previous reports suggest that enzyme replacement therapy is more effective in polyclonal hypergammaglobulinaemia than in monoclonal gammopathy.

INTRODUCTION:Monoclonal gammopathies of undetermined significance (MGUS) occur in up to 1% of persons aged 50 years or older. The risk of its progression to multiple myeloma or related disorders is also approximately 1% per year.OBJECTIVES:Our study had two aims: to describe the risk of malignant progression of patients examined in our center for MGUS, and to identify predictors of this malignant progression.METHODS:We retrospectively reviewed the medical records of patients with MGUS seen in our center from 1980 through 1995. Information about progression came either from the medical file or from responses to questionnaires sent to patients' general practitioners.RESULTS:The study included 190 patients. Median follow-up was 84 months (range: 12-240 months). MGUS remained stable for 128 patients (67.37%), whose median follow-up was 96 months. Malignant transformations occurred in 41 patients (21.58%). The median interval from diagnosis of MGUS to diagnosis of a lymphoplasma cell proliferative disorder was 49 months. The cumulative probability of progression was 13.05% at 5 years and 25.14% at 10 years. The initial concentration of serum monoclonal protein was a significant predictor of progression (threshold value: 15 g/L).DISCUSSION:The cumulative probability of progression in our study is higher than that observed elsewhere. Our results may well be biased by the short follow-up period and selective referrals.CONCLUSION:The initial concentration of serum monoclonal protein is a significant predictor of malignant progression of MGUS.

REASONS FOR PERFORMING STUDY:Fatty acid supplementation could modulate erythrocyte membrane fluidity in horses at rest and during exercise, but information is lacking on the effect of exercise.OBJECTIVES:To assess the effect of exercise with, and without, an oral antioxidant supplementation enriched with n-3 fatty acids on erythrocyte membrane fluidity (EMF) and fatty acid composition in eventing horses.METHODS:Twelve healthy and regularly trained horses were divided randomly into 2 groups: group S received an oral antioxidant cocktail enriched in n-3 fatty acid (alphatocopherol, eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) whereas group P was placebo-treated. At the end of 4 weeks, all horses performed a standardised exercise test (ET) under field conditions. Venous blood was sampled before starting treatment (TO), immediately before (T1) as well as 15 min (T2) and 24 h (T3) after ET. Spin labelled (16-DOXYL-stearic acid) red blood cell membranes were characterised using the relaxation correlation time (Tc in inverse proportion to EMF). Fatty acid composition (%) of the membrane was determined by gas-liquid chromatography.RESULTS:Supplementation did not induce changes in EMF (T1 vs. TO) but significant changes in membrane composition were observed and there were increases in n-3 polyunsaturated fatty acid PUFA, n-3/n-6 ratio, and total n-3 fatty acids. Exercise (T2 vs. T1) induced a significant decrease of EMF in group P (Tc: +19%, P<0.05) and nonsignificant decrease in group S (Tc: +5%), whereas membrane fatty acid composition did not change in either group. During the recovery period (T3 vs. T2), EMF decreased significantly in group S (Tc: +29%, P<0.05) and nonsignificantly in group P (Tc: +18%) without any significant changes in fatty acid composition.CONCLUSION AND POTENTIAL RELEVANCE:An enriched oral antioxidant supplementation induced changes in membrane composition, which modulated the decrease in EMF induced by exercise. Long chain n-3 fatty acid supplementation might therefore be beneficial.

Introduction > Monoclonal gammopathies of undetermined significance (MGUS) occur in up to I% of persons aged 50 years or older The risk of its progression to multiple myeloma or related disorders is also approximately 7% per yearObjectives > Our study hod two aims: to describe the risk of malignant progression of patients examined in our center for MGUS, and to identify predictors of this malignant progression. Methods > We retrospectively reviewed the medical records of patients with MGUS seen in our center from 1980 through 1995. Information about progression come either from the medical file or from responses to questionnaires sent to patients' general practitioners.Results > The study included 190 patients. Median follow-up was 84 months (range: 12-240 months). MGUS remained stable for 128 patients (61.37%), whose median follow-up was 96 months.Malignant transformations occurred in 41 patients (21,58%). The median interval from diagnosis of MGUS to diagnosis of a lymphoplasma cell proliferative disorder was 49 months. The cumulative probability of progression was 13.050% at 5 years and 25.14% at 10 years. The initial concentration of serum monoclonal protein was a significant predictor of progression (threshold value: 15 g/L). Discussion > The cumulative probability of progression in our study is higher than that observed elsewhere. our results may well he biased by the short follow-up period and selective referrals.Conclusion > The initial concentration of serum monoclonal protein is G significant predictor of malignant progression of MGUS.

Plasma cholesterol efflux capacity is stimulated during postprandial (PP) hypertriglycerdemia. Plasma cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are the key proteins in lipoprotein metabolism and remodelling, but their role during the PP cholesterol efflux process remains indeterminate. The aim of this study was to determine the effect of a fatty meal intake on plasma CETP and PLTP activities, and the capacity of plasma to promote cholesterol efflux, as well as to evaluate the relationship between these three key mechanisms of the reverse cholesterol transport process.CETP and PLTP activities and the cholesterol efflux capacity of plasma were measured over eight hours following a fatty meal (1000 kcal, 62% fat) in 13 normolipidemic men. CETP activity and the cholesterol efflux capacity of plasma from Fu5AH cells increased after the meal, reaching a maximum after eight hours (respectively 32%, p = 0.06, and 6.5%, p = 0.045), whereas PLTP activity remained unchanged. CETP and PLTP activities did not correlate with plasma cholesterol efflux capacity in the fasting or PP state. Plasma CETP activity in the fasting state positively correlated with the plasma non-esterified fatty acid (NEFA) levels, but no correlation was found with any lipid or apolipoprotein postprandially. The cholesterol efflux capacity of plasma correlated positively with high-density lipoprotein (HDL) components, the best correlation being with the HDL phospholipid fraction in both the fasting and PP states.These findings suggest that plasma CETP and PLTP activities in healthy normolipidemic subjects are differently regulated in the PP state, and are not correlated with the increased cholesterol efflux capacity of PP plasma. HDL-phospholipid remains the key factor in the regulation of the capacity of plasma to promote Fu5AH cell cholesterol efflux.

Les maladies cardiovasculaires représentent le premier problème de santé publique des pays occidentaux. Des études récentes de prévention secondaire ont montré que des régimes maintenant un apport en acide oléique de 10 à 13% de l’apport énergétique total (AET) pouvaient protéger de l’apparition d’accidents cardio-vasculaires [8], mais augmenter cet apport d’acide oléique à plus de 20% de l’AET pourrait limiter cet effet bénéfique en induisant une augmentation du LDL-C [12, 34]. Grundy, dans le but de clarifier le ratio nécessaire entre acides gras saturés et insaturés (mono and poly), concluait en 1997 à d’« insufficient data for recommended Oleic intake », et proposait pour le moment 15-16% d’acide oléique à titre de « reasonable compromise ». L’objectif de notre étude était de définir des rapports entre acides oléique, linoléique et alphalinolénique (OL/LA/ALA ratio) et de valider l’apport oléique après avoir stabilisé le rapport linoléique/alphalinolénique du régime d’hommes normolipidémiques (n = 40). Pour atteindre 11, 13 et 16% de l’AET sous forme d’acide oléique, nous avons utilisé des huiles de tournesol, de tournesol oléique (HOSO) et de colza pour obtenir des mélanges spécifiques ajustés à l’apport en acides gras proposés au protocole. Chacun de ces trois régimes (comportant 11, 13 et 16% d’acide oléique) a été suivi pendant 16 semaines et l’épuration postprandiale d’un repas gras (1 000 Kcal, 62,5% lipides) a été suivie pendant 8 heures à la fin de chaque période de régime. Les résultats indiquent que la stabilité des paramètres d’athérogenèse évalués à jeun et en postprandial est maintenue à un niveau favorable après ces régimes à 11, 13 et 16% d’apport en acide oléique : il n’y a pas de différences statistiques significatives sur les concentrations à jeun de LDL-C, non-HDL-C, HDL-C, TG, ApoB, ApoAI ou sur l’amplitude de la réponse postprandiale des TG. Ainsi les rapports ApoB/AI, LDL-C/HDL-C et non-HDL-C/HDL-C sont stabilisés. Ces observations permettent de conclure que la consommation d’acide oléique comprise entre 11 et 16% d’AET (soit 28 g à 44 g) de la ration alimentaire pourrait correspondre aux limites de flexibilité de ces apports, dans le cadre d’un apport calorique total de l’ordre de 2 000 à 2 500 Kcal et compte tenu des autres éléments entrant dans la composition du régime. Les limites de flexibilité des apports en acides oléique, linoléique et alphalinolénique en pourcentage d’AET du régime alimentaire pourraient être définies comme suit : 11-16% (soit 28 g à 44 g) d’acide oléique, 4-6% (soit 9 g à 13 g) d’acide linoléique, 1% (soit 1,5 g à 3 g) d’alphalinolénique (pour 60% en position sn2). Soit des rapports 18:1/18:2n-6/18:3n-3 de l’ordre de 11-16/4-6/1 en % de l’AET.

Background: Serum paraoxonase (PON) activity and the relevance of PON gene polymorphism in vascular complications of type 2 diabetic patients were investigated in a case-control study.Methods: The population included 105 control subjects, 96 diabetic patients without vascular complications and 71 diabetics with vascular complications.Results: Serum PON activity was significantly decreased (p < 0.001) in diabetic patients without vascular complications: 207 IU (25-817) compared with the controls: 259 IU (24-950). Although serum PON activity was also decreased: 232 IU (34-797) in the population with vascular complications, the difference was not statistically significant (p = 0.11). The Q192 allele frequency is significantly higher (p < 0.005) in diabetics without vascular complications (77%), and with vascular complications (73%) than in the controls (63%). No significant association was found between either PON(1)55 L/M and PON(2)311 C/S gene polymorphisms and vascular complications.Conclusions: The difference in allele frequency for the PON1 Q/R 192 gene polymorphism may be the cause of the low paraoxonase activity observed in type 2 diabetes mellitus. Further studies need to be conducted to elucidate the role of the enzyme in the development of vascular complications in diabetes.

Lipoprotein(a) (Lp(a)) with atherogenic and thrombotic properties has been frequently studied in diabetes, because a high cardiovascular risk has been reported both in type 1 and type 2 diabetes. Few studies have considered genetic factors, especially the isoforms of apolipoprotein(a). The aim of this work is to determine the distribution of apo(a) phenotypes in the serum of 148 diabetic patients (59 type 1, 89 type 2) with or without vascular complications. Apo(a) phenotypes are determined using 4-15% sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by immunoblotting (PhastSystem - Pharmacia). An inverse relationship is observed between Lp(a) serum concentration and the apparent molecular mass of apo(a) isoforms: type 1 r=- 0.61, p<0.01; type 2 r=- 0.55, p<0.01. The frequency of apo(a) isoforms is significantly different between type 1 and type 2 diabetes mellitus. A higher prevalence of isoforms of low molecular weight was observed in the type 2 diabetic population.

Most frequently, in routine laboratories, C-HDL is measured in the supernatant after precipitation of apolipoprotein B-containing lipoproteins by the sodium phosphotungstate/magnesium chloride reagent (PTA). This method involves precipitation, centrifugation and decantation steps which prevent full automation of the measurement and decrease the accuracy of the results. Recently, three direct assays for C-HDL including alpha-cyclodextrin sulphate (alpha-CD), polyanions/detergents (PA-D) or antibodies anti-beta-lipoproteins (AC) have been commercialized, in which all steps are fully managed by automated analyzers. These new methods have been compared to the conventional procedure (PTA), in multicenter studies among six laboratories using different analyzers. The C-HDL values measured by the alpha-CD and PA-D assays correlated well with those of the PTA method (r > 0.98), on most of the analyzers. With the AC assay, only the results obtained with the Hitachi 717 analyzer were correlated with C-HDL values of the PTA method. The linearity and specificity studies were evaluated in the laboratory A on a Kone Specific analyzer. The alpha-CD and PA-D assays were linear for C-HDL values from 0 to 5.56 mmol/l, as observed by increasing amounts of HDL2 + HDL3 or serum without lipoprotein isolated by ultracentrifugation. The specificity of these two methods was evaluated simultaneously, by adding various amounts of lipoproteins isolated by sequential ultracentrifugation. No interference was observed when adding chylomicrons up to 13.4 mmol/l of triglycerides for both methods. Inversely, increased C-HDL values were observed with added VLDL from 6 mmol/l of triglycerides for the PA-D assay and from 8 mmol/l for the alpha-CD assay. No interference was observed with added LDL up to 11.5 mmol/l of C-LDL for the alpha-CD assay and up to 6.7 mmol/l for the PA-D assay. In conclusion, the present multicenter evaluation demonstrates that the new procedures for the direct automation of C-HDL are easy and accurate and most of them correlated well with the classical precipitation method. In addition the study provides arguments for a choice between the different direct C-HDL methods.