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Biomedical subjects

B Bousquet

Publications and source records attributed to B Bousquet.

At least 19 recordsLinked to original sources

Measurement of the positive muon anomalous magnetic moment to 0.7 ppm.

A higher precision measurement of the anomalous g value, a(mu)=(g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron, based on data collected in the year 2000. The result a(mu(+))=11 659 204(7)(5)x10(-10) (0.7 ppm) is in good agreement with previous measurements and has an error about one-half that of the combined previous data. The present world average experimental value is a(mu)(expt)=11 659 203(8)x10(-10) (0.7 ppm).

Journal Article↗

Melanoma progression and serum L-dopa/L-tyrosine ratio: a comparison with S100B.

The challenge to find a reliable tumour marker for the management of melanoma patients still remains. In this study, the serum L-dopa/L-tyrosine ratio was compared with serum S100B as a reference marker. A total of 89 melanoma patients were sampled and staged according to the American Joint Committee on Cancer (AJCC) classification. Of these, 19 stage III and 28 stage IV patients were evaluated for disease progression at 1.5 years and 6 months post-sampling, respectively. Serum L-dopa and L-tyrosine were measured by high performance liquid chromatography (HPLC) (normal value for ratio < 16 x 10(-5)) and S100B using the LIA-mat Sangtec 100 assay (normal value < 0.10 microg/l). Non-parametric tests (Kruskal-Wallis analysis of variance, Dunn's and Spearman) were used for the statistical analysis. The median serum L-dopa/L-tyrosine ratio was 16.0 x 10(-5) (range 2.7-545.1 x 10-5 and the median S100B level was 0.15 microg/l (range < 0.10-13.8 microg/l), with a sensitivity of 51% for the ratio and 66% for S100B. There was a 47% discordance and no correlation between the two markers (r = 0.149). The ratio was higher in stage IV than in other stages (P < 0.05), as was the S100B level (P < 0.0001). Both markers were higher in patients with evolutive disease (n = 23) than in stable patients (n = 24), with values of 20.8 x 10(-5) versus 13.1 x 10(-5) for the ratio (P < 0.05) and 0.89 microg/l versus 0.16 microg/l for S100B (P < 0.001); for the ratio, this difference was more pronounced in stage III than in stage IV patients. The overall sensitivity and specificity of the markers to predict disease progression were 78% and 67%, respectively, for the ratio, and 74% and 83%, respectively, for S100B (using an ROC cut-off of 0.38 microg/l). In conclusion, the serum L-dopa/L-tyrosine ratio correlates with melanoma progression and has predictive value, especially in stage III patients. This tumour marker, like S100B, could serve as an additional tool in the management of melanoma.

Adult↗

Micellar electrokinetic capillary chromatography quantification of cytosine arabinoside and its metabolite, uracil arabinoside, in human serum.

Cytosine arabinoside (Ara-C) is widely used to induce remission in adult granulocytic leukemia. High doses can be infused in refractory leukemia or in relapse. After injection, Ara-C is quickly metabolized to uracil arabinoside (Ara-U), the main inactive metabolite. We here described a micellar electrokinetic capillary chromatography (MECC) method to simultaneously determine Ara-C/Ara-U in human serum using 6-O-methylguanine as an internal standard. The assay was linear from 6.25 to 200 microg/ml with a quantification limit between 3 and 6 microg/ml. The analytical precision was satisfactory between 2 and 4.3% (within-run) and 3.7 and 7.3% (between-runs). This assay was applied to the analysis of serum from acute granulocytic leukemia patient treated by high doses cytarabine (3 g/m2 body surface).

Antimetabolites, Antineoplastic↗

Simultaneous determination of total plasma glutathione, homocysteine, cysteinylglycine, and methionine by high-performance liquid chromatography with electrochemical detection.

We here describe an ion-exchange high-performance liquid chromatography technique with electrochemical detection for rapid quantification of glutathione, homocysteine, cysteinylglycine, and methionine. The analytical validation of the technique showed within-assay and between-assay coefficients of variation between 3.1 and 4.3%, and 3.7 and 8.6%, respectively. Percentages of recovery for overload and dilution tests were between 87 and 120%. Detection limits were 1 micromol/L for methionine and 0.5 micromol/L for other compounds. There was no interference with any physiological and pharmacological substances possessing a thiol function. Aminothiol concentrations determined in 100 control subjects (50 women and 50 men) showed no age- or sex-rated differences for except for homocysteine which was increased (+ 28%) in oldest subjects of both sexes. In 60 patients at risk (30 with chronic renal failure, 30 with diabetes), homocysteine concentration was significantly increased. No variation in other aminothiols was observed in diabetic subjects. Methionine was decreased and cysteinylglycine was increased in patients with chronic renal failure. The present technique-rapid, easy to use, and reliable-appears suitable for routine application in the exploration of aminothiol metabolic pathways including mechanisms of hyperhomocysteinemia.

Aging↗

Evaluation of standard tyrosinase RT-PCR in melanoma patients by the use of the LightCycler system.

BACKGROUND: Haematogenous spread influences outcome in melanoma patients. The clinical relevance of detecting circulating melanoma cells in peripheral blood by tyrosinase mRNA RT-PCR is, however, questioned as rates of positivity considerably vary between studies. Standard tyrosinase-nested RT-PCR was here compared with a real-time PCR technique. METHODS: Forty-three blood samples from 20 stage III--IV melanoma patients were analyzed. Mononuclear cells were isolated using a Ficoll Hypaque gradient technique. Total RNA extracted by the acid guanidinum thiocyanate-phenol-chloroform method was reverse transcribed using random hexamers or specific primers. Standard tyrosinase-nested PCR was performed on Touchdown machine (Hybaid) and real-time PCR on a LightCycler instrument (Roche). RESULTS: Only two samples from stage IV patients (one from random hexamers, one from antisense primers) were found tyrosinase positive with a 100% agreement between the two PCR techniques. A 10-fold dilution of the first-round products improved the PCR kinetic and the final amount of amplified product of positive samples, but not the rate of positivity. CONCLUSIONS: Efficiency of the PCR reaction can be monitored in an online fashion by the LightCycler instrument allowing technical improvements. However, tyrosinase mRNA RT-PCR cannot be yet considered as a useful technique in the monitoring of melanoma patients.

Adult↗

Comparison of urinary markers for bone resorption in multiple myeloma.

Multiple myeloma causes extensive bone remodeling. Classical biochemical markers such as urinary calcium have poor sensitivity for detecting multiple myeloma bone remodeling. New biochemicals have been developed including a carboxyterminal telopeptide of collagen I (CTX). We used an immunoenzymatic assay to determine urinary CTX in 60 patients with multiple myeloma. This marker was evaluated with regard to total pyridinolines, urinary calcium, radiological features, pain and response to treatment with bisphosphonates. In patients with bone involvement, CTX concentrations were significantly higher (+230%) than those of deoxypyridinoline (DPD) (+175%) and pyridinolines (PYD) (+130%). In all patients we have found a close correlation between CTX and DPD but not between CTX and PYD. Compared to radiological features, CTX was more sensitive (97%) and specific (96%) than DPD. After treatment by bisphosphonates, the fall in CTX concentrations was paralleled to urinary calcium and more marked than pyridinolines. Although our results need to be confirmed, CTX appears to be a potential marker to explore bone involvement in multiple myeloma.

Adult↗

Determination of 4-hydroxyifosfamide concomitantly with ifosfamide and its dechloroethylated metabolites using gas chromatography and a nitrogen phosphorus-selective detector.

A sensitive gas chromatographic (GC)/nitrogen phosphorus detection (NPD) system was developed for the determination of the antitumor drug ifosfamide (Ifos) and its 2-dechloroethylifosfamide (2-Difos), 3-dechloroethylifosfamide (3-Difos) and 4-hydroxyifosfamide (4-OHIfos) metabolites in human blood. 4-OHIfos was analyzed after coupling with a trapping agent and was used as an indicator of isophosphoramide mustard (IPM). Ifos and its metabolites 2-DIfos, 3-DIfos, 4-OHIfos and the internal standard (trofosfamide) were extracted into chloroform and then resolved by gas chromatography using a Hewlett Packard HP5 capillary column cross-linked with 5% phenyl methyl silicone (30 m; 530 microm I.D.; 2.65 microm film thickness). Precision and accuracy of the assay were determined over a three-day period and a concentration range of 3.25-50 microg/ml for Ifos, 0.8-14 microg/ml for 2D-Ifos, 0.6-10 microg/ml for 3D-Ifos and 0.08-1.40 microg/ml for 4-OHIfos. The limit of quantitation was set at 3.25, 0.80, 0.62 and 0.08 microg/ml, respectively, for Ifos, 2-DIfos, 3-DIfos and 4-OHIfos. The intra- and inter-day coefficients of variation and accuracies were less than 20%, except for a low concentration 4-OHIfos. This assay was then used to provide pharmacokinetic data on antitumor and toxicologic effects following intravenous infusion of Ifos.

Antineoplastic Agents, Alkylating↗

Quantification of residual dimethyl sulfoxide in supernatants of haematopoietic stem cells by capillary zone electrophoresis.

Dimethyl sulfoxide (DMSO) is a chemical compound that is used to preserve haematopoietic stem cells during freezing at -180 degrees C. As DMSO is largely removed by washing before reinjection of cells into a patient, accidents (notably cardiovascular) are infrequent. The lack of a method for evaluating the residual quantities of this product led us to develop a technique for assaying DMSO by capillary zone electrophoresis without extraction. This simple, rapid and precise technique was applied to the supernatant of cell pellets of thirteen patients before and after washing.

Culture Media↗

Urinary carboxyterminal telopeptide of collagen I as a potential marker of bone metastases chemotherapy monitoring in breast cancer.

Breast cancers frequently have osteoclastic bone metastases that are difficult to monitor and treat. Bone scintigraphy with 99mTc-labeled biphosphonates is still the reference method for detecting and localizing bone involvement. Classical biochemical markers such as urinary calcium have poor sensitivity for detecting and monitoring metastases of breast cancers. New biochemical markers for the study of bone remodeling have recently been developed, including a degradation product of the C-terminal end of the telopeptide of type I collagen (CTX). We used an immunoenzymatic assay technique for urinary CTX in 84 pre- and post-menopausal women and demonstrated a correlation between scintigraphic scores and urinary CTX concentrations. CTX values are significantly different between the control group and patients with bone metastasis, except those with score 0. There is a regular increase in urinary CTX concentration from score 0 (no abnormal uptake) to score 4 (diffuse carcinomatosis). There is no significant variation between control population and score 0 to 3 for urinary calcium. Only women with scintigraphic score 4 have significantly increased urinary calcium concentrations. Measuring CTX in pre- and post-menopausal patients during breast cancer chemotherapy might be of great interest for monitoring the development of metastases and the therapeutic efficacy of chemotherapy.

Adult↗

Simultaneous analysis of tyrosinase mRNA and markers of tyrosinase activity in the blood of patients with metastatic melanoma.

Determination of blood tyrosinase mRNA by RT-PCR and markers of tyrosinase activity (L-DOPA/L-tyrosine ratio) by HPLC have been proposed as biological tools for the detection of metastases in melanoma patients. We prospectively evaluated their significance and clinical value in a group of 30 stage III (n = 10) and IV (n = 20) melanoma patients and one with melanosis of Dubreuilh. L-DOPA/L-tyrosine ratio was elevated in 30% of stage III, 41% of stage IV patients (range: 7.5-261.0 x 10(5)) and in melanosis of Dubreuilh (184.8) (reference values: 6-16 X 10(5)). One stage III and four stage IV melanoma patients were positive for tyrosinase mRNA. In stage IV patients, tyrosinase mRNA positivity was associated with disease progression (P<0.01). The presence of tyrosinase mRNA in blood is more related to clinical status than level of melanin precursors, which probably reflects tumor burden.

Adult↗

Development of metastases in malignant melanoma is associated with an increase in the plasma L-dopa/L-tyrosine ratio.

In this prospective study we evaluated a new biochemical approach in which the plasma ratio of the melanin precursors L-dopa and L-tyrosine serves as a marker of metastatic dissemination in malignant melanoma. Control values (11.20 x 10(-5) +/- 2.92 x 10(-5)) were determined. The L-dopa/L-tyrosine ratio was evaluated in the plasma of 90 patients with malignant melanoma (stage I/II, n = 33; stage III, n = 33; stage IV, n = 24) classified according to the tumour/node/metastasis (pTNM) classification. A total of 106 samples were studied. Serial measurements were performed in eight stage III-IV patients. The L-dopa/L-tyrosine ratio was significantly elevated in melanoma patients with clinical stage III (15.23 x 10(-5) +/- 3.34 x 10(-5)) compared with stage I (10.88 x 10(-5) +/- 2.52 x 10(-5)). Stage IV patients showed a significant increase in the plasma L-dopa/L-tyrosine ratio (45.73 x 10(-5) +/- 61.75 x 10(-5)) compared with the other groups. The ratio was higher for those with two rather than one metastatic site and markedly higher for those with widespread metastases. The development of metastases was associated with an increase in plasma L-dopa, a decrease in plasma L-tyrosine and a significant increase in the plasma L-dopa/L-tyrosine ratio. These data suggest that the plasma L-dopa/L-tyrosine ratio reflects the tumour burden and correlates with the progression of malignant melanoma.

Adult↗

Changes in plasma cystatin C after renal transplantation and acute rejection in adults.

BACKGROUND: Cystatin C has recently been proposed as an alternative marker of glomerular filtration rate. The diagnostic value of plasma cystatin C for the longitudinal assessment of kidney function after renal transplantation, however, has not been addressed. METHODS: Renal function was evaluated in 30 adults receiving renal transplants (46 +/- 9 years, mean +/- SD) and in 56 healthy controls (38 +/- 10 years) using cystatin C. Plasma cystatin C was determined daily starting the day of surgery and for 3 weeks after surgery by an immunonephelometric assay. RESULTS: Plasma concentration significantly decreased during the first week (-44% vs -29% for creatinine). Plasma cystatin C correlated with plasma creatinine (r = 0.741; P <0.0001) and the reciprocal of the creatinine clearance estimated by the Cockcroft-Gault formula (r = 0.882; P <0.001). In all three cases of acute renal impairment, the increase in plasma cystatin C values was more prominent than that of creatinine. CONCLUSIONS: Plasma cystatin C is an alternative and accurate marker of allograft function in adult transplant patients. Increased sensitivity compared with creatinine for the detection of acute reduction in glomerular filtration rate allows in some cases a more rapid diagnosis of acute rejection or treatment nephrotoxicity.

Adult↗

[Psychosocial effects of angina. Results of a cross-sectional survey of 3,654 patients].

The consequences of angina were assessed by a questionnaire completed by 1,528 out-hospital doctors (79% of general practitioners, 21% of cardiologists) on 3,654 patients. This population comprised 2,304 men (64%) and 1,282 women (36%) with a mean age of 69.5 years (men: 67.1, women: 73.8 years). Previous myocardial infarction was present in 36.6% of cases and the average number of angina attacks was 3.1 per month. Angina seemed to affect the social behaviour of 25 to 30% of patients, the affective behaviour of 40% of patients and everyday life style in 60% of cases. Sixty per cent of patients had difficulties in their work and 60% also had psychological consequences of the angina. The social consequences of angina were different according to the patient's gender. Women were more affected in family life and men in their affective behaviour. The psychological consequences were also different: women were more likely to be anxious or depressed whereas men were usually more irritable. The incidence of anxio-depressive reactions with age was not studied (the female population was older). The higher incidence of anxio-depressive symptoms in women may be partially explained by their age at the time of diagnosis and the difference in prognosis between men and women when coronary artery disease is established.

Aged↗

Sodium dodecyl sulfate-agarose gel electrophoresis of urinary proteins: application to multiple myeloma.

We evaluated a new sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) for urinary protein analysis in patients with multiple myeloma (MM; n = 47; ages, 62 +/- 2 years, mean +/- SE). Abnormal proteinuria (mean = 1872 +/- 360 mg/24 h) was present in 95% of the samples; 75% of the patients had some sign of renal dysfunction (glomerular and/or tubular) according to their SDS-AGE pattern. A band suggesting Bence Jones proteinuria (BJP) was detected in 40 vs 33 specimens by routine AGE. Immunofixation identified BJP in 38 patients; the calculated sensitivity of SDS-AGE for BJP was 97%. Excellent correlation (P <0.0001) was obtained with routine AGE (r = 0.994) and immunonephelometry (r = 0.963) for light chain quantification. SDS-AGE allows easy evaluation of renal dysfunction and shows high sensitivity for BJP detection. In a specialized laboratory, it is useful for following the progress of MM patients through the semiquantification of BJP.

Adolescent↗

Determination of the L-DOPA/L-tyrosine ratio in human plasma by high-performance liquid chromatography. Usefulness as a marker in metastatic malignant melanoma.

A first procedure was devised for determining 3,4-dihydroxyphenylalanine (L-DOPA) in human plasma by isocratic RP-HPLC coupled with electrochemical detection. A second procedure was devised for determining 3-hydroxyphenylalanine (L-tyrosine) in human plasma by isocratic RP-HPLC coupled with fluorescence detection. These methods were used to ascertain the L-DOPA/L-tyrosine ratio in plasma of patients with melanoma. Reference values were established by analysis of the L-DOPA/L-tyrosine ratio in the plasma of 35 normal healthy subjects. For 29 patients diagnosed as having melanoma without metastasis, the L-DOPA/L-tyrosine (11.96 x 10(-5) +/- 2.69 x 10(-5)) level was not significantly different from that of 35 normal controls (11.20 x 10(-5) +/- 2.92 x 10(-5)). However, this level was significantly increased (p < 0.05) in the plasma of 17 patients with developing metastasis (21.02 x 10(-5) +/- 4.68 x 10(-5)).

Biomarkers, Tumor↗

Magnesium, total calcium, phosphorus, copper, and zinc in plasma and erythrocytes of venous cord blood from infants of diabetic mothers: comparison with a reference group by logistic discriminant analysis.

Concentrations of magnesium (Mg), total calcium (Ca), phosphorus (P), copper (Cu), and zinc (Zn) were investigated in plasma (Pl) and erythrocytes (Erc) of venous cord blood of 44 infants of diabetic mothers (IDMs). These same concentrations plus total glycohemoglobin and fructosamine were determined at delivery in a subset of 15 mothers of these infants. Mineral results for IDMs were compared with those for 66 apparently healthy newborns. The duration of gestation in the two groups was significantly different (P < 0.001). After adjustment for gestational age, the mean (+/- SD) differences between groups were significant for birth weight, head circumference, Erc-Mg (1.71 +/- 0.17 for IDMs vs 1.76 +/- 0.15 mmol/L for control subjects), Pl-Ca (1.96 +/- 0.32 vs 2.48 +/- 0.22 mmol/L), Pl-P (1.99 +/- 0.40 vs 1.57 +/- 0.25 mmol/L), and Erc-Cu (10.9 +/- 2.41 vs 12.9 +/- 3.00 mumol/L), but not for Erc-Zn (33.0 +/- 18.3 vs 40.4 +/- 13.6 mumol/L). The variable that best discriminated between the two infant groups after adjustment for gestational age was Pl-Ca. In the 15 mothers, Pl-Mg (0.67 +/- 0.07 mmol/L) and Pl-Ca (1.66 +/- 0.21 mmol/L) concentrations were low, Pl-Zn (9.81 +/- 3.40 mumol/L) was normal, and Pl-Cu (33.5 +/- 10.7 mumol/L) was above normal. Correlations between total glycohemoglobin and mineral values of the mothers or paired IDM mineral values were not significant. The concentration of Pl-Ca was positively correlated with Erc-Cu (P < 0.001) and Pl-Cu (P < 0.05) in the comparison group newborns but not in the IDMs.

Calcium↗

Association between magnesium, calcium, phosphorus, copper, and zinc in umbilical cord plasma and erythrocytes, and the gestational age and growth variables of full-term newborns.

We determined reference values in umbilical cord plasma and erythrocytes for magnesium, total calcium, phosphorus, copper, and zinc, and then calculated correlations and stepwise-regression equations in 66 white full-term newborn infants (35 boys, 31 girls). Only infants meeting certain optimal criteria and benefiting from excellent maternal conditions and uncomplicated pregnancies were included. There were no significant sex-related differences at birth among the variables studied. Gestational age was positively correlated with erythrocyte zinc (P less than 0.001), and plasma calcium was positively correlated with erythrocyte copper (P less than 0.001). Plasma copper proved to be the most significant variable in the stepwise-regression equation for birth height as the dependent variable. The most significant regressors accounting for birth weight were erythrocyte zinc followed by plasma zinc.

Birth Weight↗