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.

[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.

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.

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.

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.

Level of plasma fibronectin in patients with breast cancer.

Plasma fibronectin was determined by laser nephelometric immunoassay in two populations: healthy individuals and patients with metastatic or non-metastatic breast cancer. The results showed that the fibronectin concentration was higher in the patient group than in the healthy controls of similar age, with a significant difference (p less than 0.05). The patients who had metastatic breast cancer tended to show higher levels than those with no detectable metastasis, but such a difference was not statistically significant. Since fibronectin is sensitive to clinical events unrelated to the malignancy status, it does not seem suitable as a tumor marker.

Plasma malondialdehyde in type 1 and type 2 diabetic patients.

Malondialdehyde, a marker of lipid peroxidation, was measured as thiobarbituric acid reactive substances (TBARS) in 117 diabetic patients and 53 controls. Patients were divided into groups and subgroups according to the type of diabetes (type 1 and type 2) and the existence or not of vascular complication (macro- or micro-angiopathy). Results showed that TBARS concentrations were significantly higher in type 1 (P < 0.0001) and type 2 (P < 0.001) diabetic patients than in the control group. The plasma TBARS concentrations in type 1 and type 2 diabetic patients did not differ significantly. Among the patients with vascular disease, type 2 diabetic patients with macroangiopathy had significantly higher TBARS concentrations than patients with no vascular complication (P < 0.05). Whichever the type of diabetes, there was no correlation between TBARS concentrations and glycaemic control: glycosylated haemoglobin, fasting blood glucose. This study confirmed the existence of lipid peroxidation disorders in diabetic patients.

Cutaneous interstitial fluid protein concentrations in the inflammatory syndrome: pharmacological consequences.

Concentrations of alpha 1 acid glycoprotein, albumin, transferrin, haptoglobin, immunoglobulins G, A, M and apolipoprotein B were measured in serum and suction blister fluid from a group of individuals presenting a biologically proven inflammatory syndrome, and from a control group. Protein values in suction blister fluid did not change from the 2nd to the 3rd h after the beginning of blister formation. The ratio of the concentration of proteins in blister fluid and serum did not differ significantly between the groups. However, a 25% decrease in blister fluid albumin and a 100% increase in blister fluid alpha 1 acid glycoprotein, recorded in the inflammatory group, were worth noting, since they possibly influence the tissular distribution of some protein-binding drugs. Finally, an inverse relationship was established between the blister fluid/serum concentration ratio and the respective molar mass of each protein.

[Ceruloplasmin determination in the inflammatory reaction and during the last three months of pregnancy : choice of a technique (author's transl)]. / Du choix d'une technique de dosage de la céruloplasmine dans le syndrome inflammatoire et au cours du troisième trimestre de la grossesse.

Two methods of ceruloplasmin determination have been tested when this protein reaches its highest levels : inflammatory reaction and the last three months of pregnancy. A very good agreement between a spectrophotometric method based on oxydasis properties of ceruloplasmin and an immunoprecipitation was found in the first case. However during the last months of pregnancy, the data obtained by immunoprecipitation yield low values when compared to spectrophotometry. This results confirmed by experiments with rats indicate that the spectrophotometric method should be preferred in all circumstances.

[Critical review of 243 monoclonal immunoglobulinopathies]. / Revue critique de 243 immunoglobulinopathies monoclonales.

243 cases of monoclonal immunoglobulinopathy were seen at the CHR in Rennes over a period of three years. The authors studied successively the relationship between the monoclonal immunoglobulin and the clinical diagnosis the distribution of the monoclonal compounds according to the heavy chain class and the identification of the light chains, the distribution of the immunoglobulinopathies in terms of the age and the sex of the patients and the correlation between the clinical diagnosis and various laboratory findings (proteins concentration, concentration of normal immunoglobulins, sedimentation rate...). The results obtained are in line with the principal data in the literature concerning monoclonal immunoglobulinopathies. However, the authors demonstrated, in the studied population, a higher percentage of monoclonal IgM than is usually reported. Furthermore, these IgM immunoglobulins, present in Waldenstrom's disease and frequently seen in various other immunoglobulinopathies, were essentially found in men.

[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.

[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.

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.

[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.

[The levels of apolipoprotein A in liquor in normal and pathological pregnancies (author's transl)]. / Evolution du taux de l'apolipoprotéine A dans le liquide amniotique au cours de la grossesse normale et pathologique.

As liquor contains only HDL (High Density Lipoprotein) as a lipoprotein we have studied the changes in the levels of apolipoprotein A, which is the major component of HDL according to the duration of the pregnancy. The study has been carried out in normal and pathological pregnancies. It has been found that the level of apolipoprotein A rises from the 16th week of amenorrhoea of pregnancy to the 26th week and then gradually drops to term. The maximum level is approximately ten times greater than the level of apolipoprotein A at term (a level approximately of 1 mg per litre). This change parallels that of total proteins throughout pregnancy. We have limited our study in pathological pregnancies to the examination of the liquor at the end of pregnancy. The three pathological maternal conditions that have been most frequently found are:--diabetes,--Rhesus-immunisation,--vasculo-renal syndromes. There has been no significant change shown up in the period that we have studied, which was from the 30th to the 38th week of amenorrhoea.

[Value of the demonstration of amniotic phosphatidylglycerol in pregnancy in diabetic women]. / Intérêt de la mise en évidence du phosphatidyglycérol amniotique au cours de la grossesse chez la femme diabétique.

Correlation was made between phosphatidylglycerol (PG), L/S ratio results and respiratory distress syndrome (RDS). PG determination is an accurate predictor of fetal lung maturity in diabetic pregnancies: when it is present in amniotic fluid there is never risk of RDS for the infant.

[Amniotic fibronectin in normal pregnancy and pregnancy with fetal anencephaly]. / Fibronectine amniotique au cours de grossesses normales et de grossesses avec anencéphalie foetale.

Fibronectin, which is an important protein in plasma and in surface cells was calculated in amniotic fluid using a laser ray nephelemetric technique. In normal pregnancies (in 72 samples studied) this protein which rises towards the 18th week of amenorrhoea (mean +/- S.D.: 60.8 +/- 16.0 mg/l), decreases steadily to term (mean 14.8 +/- 8.9 mg/l). In fetal anencephaly (10 samples tested) high levels were also found but the difference as compared with normal levels was not significant. This measurement does not therefore constitute an extra way of screening for closure of the neural tube.

[Amniotic alpha 1-foetoprotein of the 17th week of pregnancies with amenorrhea (author's transl)]. / Alpha 1-foetoprotéine dans le liquide amniotique à la 17e semaine d'aménorrhée gravidique. Comparaison des résultats obtenus par électroimmunodiffusion et radioimmunologie.

The amniotic alpha 1-foetoprotein of the 17th week of pregnancies with amenorrhea was tested by electroimmunodiffusion and radioimmunology. The results show a very good correlation between both methods. We can see from this study the possibility for any laboratory to test alpha 1-foetoprotein in amniotic fluid of patients with high risk pregnancies, as the beginning of pregnancy when amniotic punction is necessary without using radioimmunology.