Effect of treatment on biclonal gammopathy associated with Gaucher disease.

The 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 beta-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.

[Epidemiology of monoclonal gammopathy in a general hospital and a university internal medicine department]. / Epidémiologie descriptive des gammapathies monoclonales. Expérience d'un centre hospitalier général et d'un service de médecine interne de centre hospitalier et universitaire.

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.

The effects of dietary N-3 and antioxidant supplementation on erythrocyte membrane fatty acid composition and fluidity in exercising horses.

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.

[Characteristics of smokers seeking smoking cessation services: the CDT programme]. / Caractéristiques des fumeurs s'adressant aux consultations de tabacologie. Analyse de la base nationale CDT.

INTRODUCTION: The development of smoking cessation clinics in France since 1999 has been accompanied by the setting up of an electronic database to evaluate the appropriateness of these services to the needs of smokers. The aim of this paper is to analyse the characteristics of smokers registered in the smoking cessation services national database. METHODS: A cross-sectional population-based study was conducted in 40 smoking cessation centres from 20 French regions. The study population included 14,574 smokers attending the smoking cessation centres that participated in building a national computerised database during the period 2001-2003. RESULTS: A significant proportion of the study population was female (51.4%), middle-aged (42.8 years), more highly educated (34% had received further education) and employed (68%). Almost half of the population was considered to be highly dependent on tobacco. Thirty-four percent of smokers had a past medical history of cardiovascular or lung disease. A history of depression was found in nearly one third of the population. CONCLUSIONS: Young people and individuals from deprived backgrounds were underrepresented, but smoking cessation services were being accessed by highly-dependent smokers and smokers with tobacco-related diseases services. More targeted smoking cessation strategies should be considered in order to improve access to smoking cessation services by more deprived groups.

Postprandial variations in the cholesteryl ester transfer protein activity, phospholipid transfer protein activity and plasma cholesterol efflux capacity in normolipidemic men.

BACKGROUND AND AIM: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Serum paraoxonase activity and paraoxonase gene polymorphism in type 2 diabetic patients with or without vascular complications.

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 PON(1) 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.

Models to predict cardiovascular risk: comparison of CART, multilayer perceptron and logistic regression.

The estimate of a multivariate risk is now required in guidelines for cardiovascular prevention. Limitations of existing statistical risk models lead to explore machine-learning methods. This study evaluates the implementation and performance of a decision tree (CART) and a multilayer perceptron (MLP) to predict cardiovascular risk from real data. The study population was randomly splitted in a learning set (n = 10,296) and a test set (n = 5,148). CART and the MLP were implemented at their best performance on the learning set and applied on the test set and compared to a logistic model. Implementation, explicative and discriminative performance criteria are considered, based on ROC analysis. Areas under ROC curves and their 95% confidence interval are 0.78 (0.75-0.81), 0.78 (0.75-0.80) and 0.76 (0.73-0.79) respectively for logistic regression, MLP and CART. Given their implementation and explicative characteristics, these methods can complement existing statistical models and contribute to the interpretation of risk.

Determination of lipoprotein(a) concentrations and apolipoprotein(a) molecular weights in diabetic patients.

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.

[Multicenter evaluation on different analyzers of three methods for direct HDL-cholesterol assay]. / Evaluation multicentrique sur différents automates d'analyses de trois méthodes de dosage direct du cholestérol-HDL.

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.

[Triclonal gammopathy and malignant immunoproliferative syndrome]. / Gammapathie triclonale et syndrome immunoprolifératif malin.

Three distinct monoclonal gammopathies were identified in the serum of a 79 year-old man. In 1972 he presented with Waldenström's macroglobulinemia IgM Kappa. Twenty years later multiple myeloma was diagnoses. Serum protein electrophoresis performed at this time showed three monoclonal bands. Immunofixation identified these bands as monoclonal IgM kappa, IgG kappa and IgA kappa. Twenty-six cases of triclonal gammopathies were previously reported. Sixteen cases were associated with malignant immuno-proliferative diseases (non-hodgkin lymphoma, Waldenström's macroglobulinemia, multiple myeloma); five cases with non-hematologic diseases; three cases were of undetermined significance. The origin of three distinct monoclonal proteins may derive from three unrelated clones or alternatively from a single clone in which an isotype switch has occurred.

Fortuitous diagnosis of the association of hemoglobin J-Broussais with beta + thalassemia.

The authors report a case, not described so far in literature, of an association of HbJ-Broussais [alpha (90 (PG2) lys-->asn beta 2] with beta + thalassemia in a young girl born of Italian father and Breton mother. This association is clinically silent. Biochemistry revealed, besides HbA, the presence of HbJ-Broussais in the proportion of 19.4% and HbA2 value of 3.9%. These percentages, slightly lower than expected, are explained. A familial study is presented.

Serum lipid, apolipoprotein and lipoparticle levels in the human fetus.

Blood collected from 62 fetuses aged 20-38 weeks of gestation was studied. The values of ten lipid parameters were determined: cholesterol (TC), triglycerides (TGs), apolipoprotein A1 (apo A1), apolipoprotein B (apo B), apolipoprotein E (apo E), total apolipoprotein CIII (apo CIII), apolipoprotein CIII present in particles containing apo B (apo CIII LpB) or not (apo CIII Lp non-B), lipoparticles A1 (LpA1), and lipoprotein a (Lp(a)). The results show that, except for apo E, all the studied parameters were present in lower concentrations than in adults and newborns, and that Lp(a) is not detectable at that stage in life.

Increase in thiobarbituric acid-reactive substances and vascular complications in type 2 diabetes mellitus.

Lipid peroxidation was assessed by measuring the concentrations of thiobarbituric acid-reactive substances in plasma from 204 Type 2 diabetic patients, relative to 107 controls. The concentrations obtained in diabetic patients (3.08 +/- 0.37 mumol/l) were significantly higher than in controls (2.80 +/- 0.34 mumol/l) (p < 0.0001). Values were also significantly increased in patients with macroangiopathy and/or microangiopathy (3.17 +/- 0.41 mumol/l), relative to patients void of vascular complications (2.92 +/- 0.34 mumol/l) (p < 0.001). Elevated concentrations were independent of the type of vascular complication and their possible associations. In patients without vascular affection, thiobarbituric acid-reactive substances were in significantly higher concentrations in hypertensive (3.07 +/- 0.36 mumol/l) than in normotensive (2.87 +/- 0.29 mumol/l) (p < 0.01) patients. There was a correlation between these values and those of total cholesterol (r = 0.46, p < 0.0001) and triglyceride (r = 0.45, p < 0.0001). Statistical analysis by multivariate logistical regression revealed that among the independent factors (TBARS, APO A1, hypertension, age), thiobarbituric acid-reactive substances constituted the parameter most strongly linked to the existence of vascular complications. This study has evidenced a lipid peroxidation disorder in non insulin- dependent diabetes mellitus, more marked in patients with vascular affection. Thiobarbituric acid-reactive substances appear to be an independent marker of vascular complications in Type 2 diabetes.

[Susceptibility of LDL to lipid peroxidation in non-insulin-dependent diabetes mellitus with or without macroangiopathy]. / Susceptibilité des LDL à la peroxydation lipidique dans le diabète non insulino-dépendant avec ou sans macroangiopathie.

Since oxidized LDL may play a role in the genesis of atheroma, which is the primary complication of non-insulin-dependent diabetes mellitus (NIDDM), we investigated whether the LDL of diabetic patients were more prone to oxidation than those of healthy controls. We therefore studied the susceptibility of LDL to oxidation by phenylhydrazine (LDL-PO) in NIDDM patients with or without macroangiopathy, and in controls. Results showed that the LDL of patients with macroangiopathy (n = 50) were more susceptible to oxidation than those of both NIDDM patients without vascular complications (n = 50) and controls (n = 50). In diabetic patients, there was a positive correlation between LDL-PO and the following parameters: total cholesterol, triglycerides, LDL cholesterol, apolipoprotein B. In contrast, there was no correlation between LDL-PO and the parameters of glycemic control (fasting glucose, HbAlc). After analyzing the composition of LDL, it appeared that LDL-PO values in diabetic patients were positively correlated with those of all LDL constituents. The increase in LDL-PO observed in the group of NIDDM patients with macroangiopathy could be a consequence of an increase in the LDL triglyceride content in these patients.

LDL sialic acid content in patients with coronary artery disease.

Low density lipoproteins (LDL) are considered to be the most atherogenic of lipoproteins. These LDL can be modified and oxidative modifications are now well known. In addition, other atherogenic modifications of LDL exist, such as desialylation. In the present study sialic acid content was determined in LDL preparations obtained from patients with coronary artery disease (CAD+) and compared with that of healthy subjects and patients without coronary heart disease (CAD-). The sialic acid concentration was found to be statistically lower (P < 0.05) in the LDL of CAD+ patients (11.6 +/- 2.7 micrograms/mg of protein) than in the LDL of controls (16.5 +/- 5.6 micrograms/mg of protein) or in the LDL of CAD- patients (15.3 +/- 3.8 micrograms/mg of protein). In subgroups of CAD+ patients divided according to the severity of the disease, no statistically significant difference was observed in LDL sialic acid content. This work confirms the presence of desialylated LDL in the sera of patients with atheroma.