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Biomedical subjects

J P Garnier

Publications and source records attributed to J P Garnier.

At least 19 recordsLinked to original sources

[General practitioners' health care for disabled patients: a survey among a panel of general practitioners in Southeastern France, in 2002].

OBJECTIVES: This article presents a study on General Practitioners' (GPs) knowledge, attitudes and practice towards disabled patients. MATERIAL: A sample of 600 private general practitioners practising in Southeastern France was selected in 2002 with a random sampling approach stratified according to age, sex, and size of the urban unit. METHOD: A standardised questionnaire was used to collect data by telephone. Results are presented as percentages. Comparisons used Pearson's chi2 test. RESULTS: Ninety percent of the GPs reported that they had to provide social assistance to their disabled patients (protecting their rights, administrative assistance, family counselor, etc.) as well as coordinating care by various other professionals. GPs frequently reported the presence of barriers that compromised the health care of disabled patients: lack of information (62.8%), time (50.2%), co-ordination between health professionals (37.7%), and training (37.7%), as well as communication problems (20.7%) and the need for assistance in clinical examinations (16.2%). More than 25% of the GPs suggested breast cancer screening (27.6%), contraceptive prevention (29.5%) or hepatitis B vaccination (29,3%) less often to their disabled than non disabled patients and 25.8% reported they had not evaluated the patients' dependency levels. CONCLUSION: This study suggests that GPs face several barriers in caring for disabled persons. A lack of knowledge may explain inappropriate care for this population. GPs need more support and guidance in dealing with disabled patients, and coordination with other health professionals must be encouraged.

Adult↗

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↗

Norepinephrine release after acute brain death abolishes the cardioprotective effects of ischemic preconditioning in rabbit.

OBJECTIVE: Brain death (BD) abolishes the infarct-limiting effect of ischemic preconditioning (IP) in rabbits. We wished to define the role of the norepinephrine storm in this observation. METHODS: Rabbits were randomized into six groups of ten animals each. In control group (CTRL), anaesthetized rabbits were subjected to 30 min left coronary marginal branch occlusion and 90 min reperfusion. In CTRL+IP group, anaesthetized rabbits were preconditioned with a 5-min ischemia and 5-min reperfusion sequence before coronary occlusion. In CTRL+NE+IP group, anaesthetized rabbits received a 10 microg/kg norepinephrine injection 90 min before IP. In BD group, rabbits were subjected to 90 min of BD before coronary occlusion. In BD+IP group, brain-dead rabbits were preconditioned before coronary occlusion. In BD+LA+IP group, rabbits received an intra-arterial bolus injection of an alpha and beta adrenoreceptor blocking agent (labetolol, 1 mg/kg) prior to brain death induction and subsequent preconditioning. BD was induced by rapid inflation of an intracranial balloon. At termination of the experiment, left ventricular volume (LVV), myocardial volume at risk (VAR) and infarct volume (IV) were determined with methylene blue and tetrazolium staining, and measured using planimetry. RESULTS: LVV was not significantly different among groups. Myocardial VAR/LVV was not significantly different between groups (CTRL, 22.5+/-6.9%; CTRL+IP, 23.3+/-2.2%; CTRL+NE+IP, 25.9+/-12.7%; BD, 19.9+/-4.8%; BD+IP, 21.7+/-3.1%; BD+LA+IP, 23.4+/-5.8%; P=NS). IV/VAR was significantly reduced in the CTRL+IP group as compared with CTRL and CTR+NE+IP groups (12.2+/-1.2 vs. 49.7+/-1.7 and 49.3+/-4.7%; P<0.0001). There was no significant difference in IV/VAR between BD and BD+IP groups. In contrast, IV/VAR was reduced in BD+LA+IP compared to BD and BD+IP groups (13.9+/-5.4 vs. 50.0+/-1.4 and 49.6+/-1.5%; P<0.001). CONCLUSION: The loss of infarct-limiting effect of IP in brain-dead rabbits is related to the massive release of norepinephrine that occurs as a consequence of BD.

Animals↗

Acute brain death abolishes the cardioprotective effects of ischemic preconditioning in the rabbit.

BACKGROUND: Myocardial preconditioning with brief coronary artery occlusions before a sustained ischemic period is reported to reduce infarct size. We wished to evaluate whether ischemic preconditioning (IP) is efficient in an experimental brain death (BD) model in the rabbit. METHODS: Rabbits were randomized into four experimental groups of eight animals each. In the control group (CTRL), anaesthetized rabbits were subjected to 30 min of left coronary marginal branch occlusion and 90 min of reperfusion without any pretreatment. In the CTRL+IP group, anaesthetized rabbits were preconditioned with a 3-min ischemia and 3-min reperfusion sequence before coronary occlusion. In the BD group, rabbits were subjected to 90 min of BD before 30 min of coronary occlusion and 90 min of reperfusion. In the BD+IP group, BD rabbits were preconditioned as in the CTRL+IP group before coronary occlusion. BD was induced by rapid inflation of an intracranial balloon and was validated by clinical and electroencephalographic examinations. At the termination of the experiment, left ventricular volume (LVV), myocardial volume at risk (VAR) and infarct volume (IV) were determined with methylene blue and tetrazolium staining and were measured using planimetry. RESULTS: LW was not significantly different among the four experimental groups (CTRL, 6.54+/-0.90 cm3; CTRL+IP, 5.92+/-0.60 cm3; BD, 5.87+/-0.81 cm3; BD+IP, 6.16+/-0.95 cm3; P=ns). Furthermore, myocardial VAR, expressed as a percentage of LVV, was not significantly different between groups (CTRL, 20.0+/-4.2%; CTRL+IP, 22.32+/-2.25%; BD, 21.38+/-3.36%; BD+IP, 21.64+/-3.39%; P=NS). IV, expressed as a percentage of VAR, was significantly reduced in the CTRL+IP group compared with the CTRL group (15.76+/-8.47% vs. 49.95+/-1.51%; P<0.0001). In contrast, there was no significant difference in IV, expressed as a percentage of VAR, between the BD and the BD+IP groups (50.0+/-1.52% vs. 49.72+/-1.58%; P=NS). CONCLUSION: The data indicate that the infarct-limiting effect of IP is lost in BD rabbits. Thus, the clinical potential of IP in the context of organ transplantation seems to be severely compromised.

Analysis of Variance↗

Pretreatment with a potassium-channel opener before prolonged cardiac storage: an evaluation in an experimental brain death model.

BACKGROUND: Pretreatment with a potassium-channel opener has been shown to improve functional recovery after long-term cardioplegic arrest. We evaluated whether pretreatment with the potassium-channel opener cromakalim is beneficial in a more clinically relevant experimental model of brain death in the rabbit. METHODS: Four groups of rabbits were studied in a 2 x 2 factorial experiment (n = 8 per group). Rabbits were subjected to a sham operation or 90 minutes of brain death induced by inflating a subdurally placed balloon. Thirty minutes before heart explantation, rabbits received either no pretreatment or an intravenous injection of cromakalim, 30 microg/kg. Hearts then received 5 hours' hypothermic storage in St. Thomas' Hospital solution and were assessed on a buffer-perfused isolated heart preparation. Hemodynamic recovery, coronary flow, and creatine kinase release were determined after 60 minutes of reperfusion. RESULTS: Systolic function and diastolic function were significantly altered in hearts explanted from brain-dead rabbits compared with hearts from rabbits having a sham operation. Cromakalim pretreatment had no significant effect on poststorage systolic or diastolic function of hearts explanted from brain-dead or sham-operation rabbits. Further, cromakalim pretreatment did not affect coronary flow or overall creatine kinase release during reperfusion. CONCLUSIONS; In vivo pretreatment of brain-dead rabbits or anesthetized rabbits with an intravenous injection of cromakalim had no significant effect on functional recovery of or enzymatic release from explanted hearts after 5 hours' hypothermic storage and 60 minutes' reperfusion. These findings underscore the importance of clinically relevant experimental models.

Animals↗

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↗

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↗

Mobilization of visceral adipose tissue related to the improvement in insulin sensitivity in response to physical training in NIDDM. Effects of branched-chain amino acid supplements.

OBJECTIVE: To evaluate the effects of an intense physical training program on abdominal fat distribution, glycemic control, and insulin sensitivity in patients with NIDDM and to determine whether branched-chain amino acid (BCAA) supplements influence these effects. RESEARCH DESIGN AND METHODS: Twenty-four patients (ages 45 +/- 2 [mean +/- SE] years, BMI 30.2 +/- 0.9 kg/m2, HbA1c 7.9 +/- 0.3%) were randomly assigned to four groups: training plus BCAA supplement (n = 6), training plus placebo (n = 6), sedentary plus BCAA supplement (n = 6), and sedentary plus placebo (n = 6). Physical training consisted of a supervised 45-min cycling exercise at 75% of their oxygen uptake peak (VO2 peak) two times per week and an intermittent exercise one time per week for 2 months. RESULTS: Patients who exercised increased their VO2 peak by 41% and their insulin sensitivity by 46%. Physical training significantly decreased abdominal fat evaluated by magnetic resonance imaging (umbilicus), with a greater loss of visceral adipose tissue (VAT) (48%) in comparison with the loss of subcutaneous adipose tissue (18%), but did not significantly affect body weight. The change in visceral abdominal fat was associated with the improvement in insulin sensitivity (r = 0.84, P = 0.001). BCAA supplementation had no effect on abdominal fat and glucose metabolism. CONCLUSIONS: Physical training resulted in an improvement in insulin sensitivity with concomitant loss of VAT and should be included in the treatment program for patients with NIDDM.

Adipose Tissue↗

The 8 kD product of the putative oncogene MTCP-1 is a mitochondrial protein.

An unusually small (8 kD) protein (p8MTCP-1) is coded by the putative oncogene MTCP-1 (also called c6.1B), involved in the translocation t(X;14)(q28;q11) associated with some mature T-cell proliferations. Here, we show by subcellular fractionation and by confocal microscopy that this protein is located in the mitochondria. This localization orientates toward a role of p8MTCP-1 in the mitochondrial metabolism which may be relevant for the oncogenic process.

Amino Acid Sequence↗

[Recommended methods for the determination of catecholamines and their metabolites in urine. Significance of results in the diagnosis and follow-up of pheochromocytoma and neuroblastoma].

Laboratory investigation of catecholamines is useful for the clinician in the diagnosis and management of phaeochromocytoma and neuroblastoma. This work summarizes current knowledge on catecholamines and their metabolites and discusses the main indications for their determination. It also examines the most practical methods for studying the secretion of these hormones, ie extraction, separation and quantification using high performance liquid chromatography coupled with electrochemical detection. The workshops attended by the members of the catecholamines working party of the French Clinical Biology Society and phaeochromocytoma and neuroblastoma specialists enabled the role of such determinations in the diagnosis and management of these diseases to be clarified.

Adolescent↗

False-positive HIV antigens related to emergence of a 25-30 kD protein detected in organ recipients.

OBJECTIVE: The routine screening of organ donors for HIV-1 since 1985 has markedly reduced the risk of acquiring infection in organ recipients. However, commercial HIV-1 p24-antigen assays reveal false-positive reactivity in certain recipients. This observation will be discussed here. METHODS: Post-transplantation sera collected sequentially from different organ recipients were tested for HIV antigen: 79 samples were from 14 kidney recipients, 57 from seven bone-marrow allografts and 18 from two heart recipients. Neutralization assays to determine specificity were performed on reactive samples. Immunoblots prepared from sera containing high levels of antigens were tested by Western blot using polyclonal anti-HIV sera. RESULTS: Abbott HIV-1-EIA kits detected non-neutralizable antigens in early post-transplantation sera from 12 kidney, five bone-marrow and two heart recipients. Using in-house immunoblots prepared from positive non-neutralizing antigen sera, a 25-30 kD protein was detected and shown to be the cause of the false HIV antigen cross-reactivity. CONCLUSION: False-positive HIV antigens related to the emergence of a 25-30 kD protein in early post-transplantation sera are detectable in transplant recipients.

Adolescent↗

[Endoscopic urethrotomy. Resection, anastomosis and cutaneous urethroplasty. Results of the Normandy Society of Urology].

Although urethrotomy alone gives poor results at 5 years, these results are greatly improved by repeated urethrotomy. This treatment is particularly useful in patients at risk, especially as it can be easily performed under local anaesthesia. The authors confirm the reliability of resection-anastomoses, the superiority of one-stage urethroplasty over two-stage urethroplasty and the poor prognosis associated with a history of repeated dilatations and infectious aetiology.

Anastomosis, Surgical↗

Platelet serotonin content and plasma tryptophan in peri- and postmenopausal women: variations with plasma oestrogen levels and depressive symptoms.

Platelet serotonin content was measured by high pressure liquid chromatography in 56 peri- and postmenopausal women, in order to study variations of this parameter with hormonal status and depressive mood symptoms. Clinical symptoms were assessed by a self-report depression symptom scale (CES-D of NIMH). Thirty-eight women with a score of 16 or more were considered as presenting depressive symptoms (mean score +/- SD = 28.8 +/- 10.5), while the others formed the control group (n = 18, score = 4.4 +/- 4.2). Platelet serotonin contents were significantly lower in the 'depressed' group (0.302 +/- 0.010 vs. 0.366 +/- 0.020 nmol 10(-8) platelets, means + SEM, P less than 0.001 by Mann-Whitney U-test). In 'depressed' women who had been treated for one or more depressive episodes, platelet 5-HT contents (0.283 +/- 0.023, n = 18, P less than 0.01) were significantly lower with respect to controls. In patients without previous episodes of depression, serotonin expressed in nmol 10(-8) platelets did not differ significantly from controls but serotonin expressed in nmol ml-1 of blood was slightly lower than control values (0.890 +/- 0.085, n = 20 vs. 1.088 +/- 0.090 nmol ml-1, n = 18, P less than 0.02). Platelet serotonin content was positively correlated to plasma oestrone and oestradiol concentrations among the control group but not in the 'depressed' group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗

[Determination of 3-methoxy-4-hydroxyphenyethylene-glycol and its urinary conjugates. Value in the diagnosis and therapeutic follow-up of depression].

In psychiatric illness like depression, difference is essential between noradrenergic and serotoninergic sources. Therefore the measurement of urinary excretion of MHPG (3-methoxy-4-hydroxy-phenylethylene-glycol) is interesting, because MHPG seems to be the best reflect of central noradrenergic activity. Analytical assay of MHPG includes an enzymatic hydrolysis and an extraction by ethyl acetate. Separation is conducted by HPLC with fluorometric detection for MHPG and VMA, and electrochemical detection for 5-HIAA, which measurement is simultaneous. Quality control is evaluated (detection limit, linearity, precision, reproducibility, hydrolysis and extraction efficiency). Control values of 15 healthy subjects are 18.9 +/- 8.0 mumol/24 h of total MHPG, 1.5 +/- 1.0 of free MHPG, 8.5 +/- 2.0 of sulfate, and 10.7 +/- 4.4 of glucuronide MHPG (m +/- 2 sigma). In our study on depression, the best biological witness seems to be the sulfate-MHPG: in 16 depressed patients without treatment, its rate is very lowered (1.2 +/- 1.2 mumol/24 h). Total and glucuronide MHPG decrease weaker than sulfate (respectively -51% and -65%), while free MHPG increases (+ 193%) versus controls. Urinary VMA and 5-HIAA, peripheric catabolites of respectively adrenalin and serotonin are not significantly altered. There is no correlation neither between urinary sulfate-MHPG and scale evaluation before treatment, nor between urinary sulfate-MHPG and clinic improvement after antidepressive treatment. At last, the association clomipramine + mianserine shows a clinic improvement faster than clomipramine only, although no significative difference appears in biological markers.

Clomipramine↗