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Biomedical subjects

A Girault

Publications and source records attributed to A Girault.

At least 19 recordsLinked to original sources

Hepatitis C virus (HCV) infection in haemodialysed patients: HCV-RNA and anti-HCV antibodies (third-generation assays).

Samples from 128 haemodialysed patients were tested by anti-HCV 2nd- and 3rd-generation assays from Ortho: 53 were positive by ELISA 2.0 and 54 (42%) by ELISA 3.0. The 54 anti-HCV-positive patients were tested by RIBA-2 and RIBA-3 and by PCR for the detection of HCV-RNA: 46 of the 47 patients (98%) reactive by RIBA-2 and 48 of the 51 patients (94%) reactive by RIBA-3 were HCV-RNA positive. Three patients with RIBA-3 indeterminate results were HCV-RNA negative. Among the 74 anti-HCV negative patients, 29 were tested by PCR with negative results. Two distinct episodes of hepatitis C have been observed in two patients during the follow-up and 44 of the 50 patients (88%) known positive for anti-HCV since at least 1989 were still viraemic in 1993. A very high correlation was found between anti-HCV antibodies reactive by RIBA and the presence of HCV-RNA. A lack of protection after a resolved infection and a high frequency of chronic disease have been observed as well as a reinfection or a reactivation of the infection in two patients.

Enzyme-Linked Immunosorbent Assay

[Prevalence of microalbuminuria in French type 2 diabetics followed by their general practitioner].

Microalbuminuria is a risk marker for cardiovascular morbidity and mortality in Type 2 diabetes. We studied microalbuminuria among French Type 2 diabetic patients in general practice, because we set-up a trial using cardiovascular events as end-points. Two thousand twenty four volunteer patients were studied for Urinary Albumin Concentration (UAC) during outpatient visit to general practitioners. The UAC was measured on first samples. If UAC was positive (> or = 20 mg/l), a second sample was requested. If UAC was positive two times, persistently elevated UAC was identified (micro or macroalbuminuria). Clinical characteristic, cardiovascular antecedents and risk factors were studied. One hundred five first samples were excluded due to urinary infection; 1,217 others displayed normal UAC (< 20 mg/l); 63.4%; group N), 557 microalbuminuria (20-200 mg/l; 29.0%, group mu), and 145 others macroalbuminuria (> 200 mg/l; 7.6%; group M). Among subjects with positive first sample, 26.5% had persistent albuminuria. There was no intergroup difference for age, but males were more frequent in groups mu or M than N (p < 10(-4)). Blood pressure and body mass index varied between groups. Smokers and alcoholic subjects were more frequent in groups mu and M than N (p = 0.037 and p = 0.0003 respectively), as were cases with myocardial infarction (p = 0.0026), lower limb arteritis (p < 10(-4)), and laser-treated diabetic retinopathy (p = 0.0002). Antihypertensive treatments were taken by 61% of the subjects. Elevated UAC (micro or macroalbuminuria) is frequent among french Type 2 diabetic patients cared by their general practitioners, and is associated with a high cardiovascular risk profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Anti-hepatitis C virus (anti-HCV) seroconversion in patients undergoing hemodialysis: comparison of second- and third-generation anti-HCV assays.

BACKGROUND: The results obtained in sequential specimens from recently infected subjects generally provide the best means of comparing the sensitivity of assays. STUDY DESIGN AND METHODS: The sensitivity of second- and third-generation assays for antibody to hepatitis C virus (HCV) was compared on sequential specimens, generally collected at monthly intervals from 45 patients undergoing hemodialysis who seroconverted for HCV between 1980 and 1990. RESULTS: Fifteen patients (33%) were positive earlier in the third-generation enzyme-linked immunosorbent assay (ELISA), with a mean difference of 17 days (range, 7-30) between the last negative and the first positive specimens. At the first rise in alanine aminotransferase, and at its peak, 63 and 91 percent of the patients, respectively, were anti-HCV positive in the third-generation ELISA. Third-generation recombinant immunoblot assay (RIBA) reacted at the same time as third-generation ELISA. Of the first specimens that were positive in second-generation ELISA, 44 percent reacted and 56 percent were indeterminate in third-generation RIBA, while 10 percent reacted, 72 percent were indeterminate, and 18 percent did not react in second-generation RIBA. From the beginning to the end of the follow-up, antibody to c33c was the most prevalent, followed in descending order by antibody to c22-3, antibody to c100-3, and antibody to NS5: 56, 54, 26, and 18 percent, respectively, at time 0, and 100, 86, 83, and 31 percent, respectively, 12 months later. CONCLUSION: Third-generation assays (both ELISA and RIBA) were more sensitive than second-generation assays in the diagnosis of HCV infection, in that positive results were obtained earlier and a higher proportion of specimens were confirmed positive in RIBA testing.

Alanine Transaminase

[Correlation between hepatitis C virus (HVC) RNA and anti-HVC antibodies in a hemodialysis population].

Polymerase chain reaction (PCR) was applied to detect HCV-RNA in 75 hemodialyzed patients. Anti-HCV status was determined by ELISA-2 and by RIBA-2 for reactive samples by ELISA. ALT levels were monthly determined during the year preceding the end of the study. For 60 patients, anti-HCV serology was known since 1989 and 39 of them were tested for the presence of HCV-RNA at least four times during the 2 preceding years. The 9 patients who were negative for anti-HCV antibodies were negative by PCR. Of the 7 patients with an indeterminate profile by RIBA-2, 3 were positive by PCR: 1/1 with C-33c band only and 2/6 with C22-3 band only. Of the 59 patients reactive by RlBA-2, 57 were HCV-RNA positive. Of the 2 HCV-RNA negative patients, one had been PCR positive before interferon therapy. Of the 38 patients without acute hepatitis tested by PCR on 5 successive samples, all the specimens of 11 and 23 patients were HCV-RNA negative and HCV-RNA positive respectively. In 4 patients, a transient viremia was observed. The group of HCV-RNA positive patients had mean ALT levels greater than those who were negative. A correlation was established between HCV infection and both the time on dialysis and the number of blood transfusions. A high concordance (97%) was observed between antibodies to HCV and HCV-RNA.

Adult

Antibodies to hepatitis C virus by second generation test in hemodialyzed patients.

To assess the prevalence and the incidence of hepatitis C virus (HCV) in a dialysis unit, we prospectively tested for anti-HCV in chronic hemodialysis patients and staff members since January 1989, using a first generation assay. Incidence was nil in staff and low in patients (3.7% in 89, 1% in 90), and prevalence was 30% in patients. In January 1991 blood samples from 115 patients were tested by first (EL1) and second generation (EL2) ELISA (Ortho Diagnostic System). Positive subjects were tested by a RIBA-2 confirmation test. Fifty-three patients were negative by all tests. Positive tests were observed in 62 patients (54%) including 36 positive in EL1 and EL2, and 26 only by EL2. All positive patients were reactive by RIBA-2 but nine were classified undetermined (only one positive band). In five patients reactivity of antibodies to 5-1-1 and C-100-3 gradually declined during the study. Second generation tests gave a better correlation with time on dialysis and blood transfusion. We conclude that second generation tests for HCV are more accurate for estimating true prevalence of HCV infection in hemodialysis units.

Adolescent

Serum lipids and urinary albumin excretion in non insulin-dependent diabetics.

The increase of urinary albumin excretion has a predictive value for cardiovascular disease in insulin-dependent and non insulin-dependent diabetics. To study the relationship between urinary albumin excretion and serum lipids, 380 non insulin-dependent diabetics, 40 to 75 yr old, with urinary albumin excretion from 0 to 200 mg/l, and normal serum creatinine (less than 150 mumol/l), were surveyed. Urinary albumin excretion, was related positively to age (r2 = 0.014; p = 0.02), to systolic blood pressure (r2 = 0.073, p = 0.0001) and diastolic blood pressure (r2 = 0.052, p = 0.0001); a negative correlation existed with HDL-cholesterol (r2 = 0.043, p = 0.0001) and Apoprotein A1 (r2 = 0.044, p = 0.0001). A stepwise regression analysis was performed and resulted in three independently contributing variables related to urinary albumin excretion: First systolic blood pressure (F = 36), second Apoprotein A1 (F 24), third hemoglobin A1C (F = 6). The presence of hypertension or insulin therapy did not modify these findings. In conclusion, serum lipid seems an important determinant of urinary albumin excretion in non insulin-dependent diabetics.

Adult

[Increase of activity of angiotensin-converting enzyme in insulin-dependent diabetic patients with permanent microalbuminuria].

Angiotensin I Converting Enzyme (ACE), which is synthesized by vascular endothelial cells, can be elevated in some diabetic subjects. To study if serum ACE can be elevated in subjects with high risk for malignant microangiopathy, 34 normotensive type I, insulin-dependent diabetic subjects with persistent microalbuminuria (30-300 mg/24 h) were compared for serum ACE activity (Liebermann's method) with 30 normotensive, normoalbuminuric type I, insulin-dependent diabetic subjects of same age (33 +/- 15 (M +/- SD) vs 39 +/- 14 years), sex (13 F/21 M vs 15 F/15 M), stage of retinopathy (14 vs 16 nil/11 vs 7 background/6 vs 4 preproliferative/3 vs 3 proliferative), HbA1c (7.7 +/- .9 vs 8.2 +/- 1.0%). Serum ACE activity of diabetic subjects were also compared with 120 age and sex related healthy controls. Serum ACE activity was higher in type I, insulin-dependent diabetic subjects with microalbuminuria than in those with normoalbuminuria (406 +/- 114 vs 359 +/- 97 IU/l; p = 0.05), or in controls (307 +/- 95 IU/l; p = 0.0001). Normoalbuminuric subjects also had higher ACE activity than controls (p = 0.02). In diabetic subjects, serum ACE activity was not related to diabetes duration (r = 0.1; ns), stage of retinopathy (r = 0.06; ns), HbA1c (r = 0.02; ns), or to blood pressure (r = 0.03; ns), but was related to urinary albumin excretion (r = 0.28; p = 0.03) in diabetic subjects. However, stage of retinopathy was related to diabetes duration (r = 0.74; p = 0.0004) and to age (r = 0.42; p = 0.003) in these subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Lipids and fatty acids of tachyzoites and purified pellicles of Toxoplasma gondii.

Various lipids were extracted from tachyzoites and from purified pellicles of Toxoplasma gondii. Extracts from both sources were found to have a low cholesterol/phospholipid ratio. The major phospholipid in these fractions was phosphatidylcholine associated with a low amount of sphingomyelin. Oleic acid represented one-third of whole-cell fatty acids and 44% of pellicular fatty acid content. The lipid composition of the pellicle of T. gondii is consistent with the previously reported high fluidity of this membrane.

Animals

Small doses of ramipril to reduce microalbuminuria in diabetic patients with incipient nephropathy independently of blood pressure changes.

The mechanism of action of angiotensin-converting enzyme (ACE) inhibitors on urinary albumin excretion (UAE) in diabetic patients remains controversial. Sixteen type 1, insulin-dependent diabetics with incipient nephropathy received ramipril, a long-acting ACE inhibitor, at hypotensive doses (treatment A: 5 mg/day, n = 8) or at nonhypotensive doses (treatment B: 1.25 mg/day, n = 8) during a 6-week, double-blind, parallel study to establish whether its antihypertensive effects could be dissociated from its local renal effects. Blood pressure, UAE, glomerular filtration rate (GFR), effective renal plasma flow (ERPF, constant [125I]iodothalamate + [131I]hippurate infusion), and ACE activity were measured before and after treatment. Blood pressure was lowered with treatment A but not with treatment B. UAE and ACE activity were reduced with both treatments. Baseline GFR and ERPF were not altered by either treatment. In the patient population as a whole, ACE inhibition correlated with a rise in ERPF and with a reduction in filtration fraction (GFR/ERPF), but not with the changes in blood pressure. Changes in UAE correlated with the changes in filtration fraction. It is concluded that renal hemodynamics may be modified by ramipril independently of blood pressure changes.

Adult

[Dissociation of hypotensive and renal hemodynamic effects of an angiotensin converting enzyme inhibitor in insulin-dependent diabetic patients with incipient nephropathy].

The mechanism of action of angiotensin converting enzyme (ACE) inhibitors on urinary albumin excretion (UAE) in diabetics is controversial. In order to dissociate the hypotensive and intrarenal effects, 16 insulin-dependant diabetics with permanent microalbuminuria (30-300 mg/24 h) without hypertension were given Ramipril, a long acting ACE inhibitor, at hypotensive (treatment A 5 mg/day; N = 8) and at sub-hypotensive doses (treatment B, 1.25 mg/day; N = 8) over a 6 week period in parallel double-blind study. Blood pressure, UAE, glomerular filtration renal blood flow (continuous 125I-Iodothalamate + 131I-Hippurate infusion) and converting enzyme activity (Liebermann's method), before and after treatment. In treatment group A, the blood pressure fell from 133 +/- 5/79 +/- 4 (mean +/- SE) to 125 +/- 4/77 +/- 2 mmHg (p less than 0.05 for systolic blood pressure) whereas it remained stable in treatment group B (132 +/- 7/79 +/- 4 to 128 +/- 5/80 +/- 4 mmHg). The UAE decreased in both groups: group A from an average of 74 (40-198) to 47 (5-202) mg/24 h (p = 0.07; group B, from an average of 77 (50-136) to 19 (15-120) mg/24 h (p less than 0.005), as did ACE activity: group A from 332 +/- 44 to 163 +/- 33 iu/l (p less than 0.004), group B from 423 +/- 39 to 191 +/- 28 iu/l (p less than 10-4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[In vitro effects of 1,25-dihydroxycholecalciferol on alkaline phosphatase and gamma-glutamyltransferase activity in hypophysectomized rats].

Effects in vitro of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on alkaline phosphatase (PAL), gamma-glutamyltransferase (gamma-GT) and acid phosphatase (PAC) activities were investigated on renal cortex from hypophysectomized rats. In these animals the biosynthesis of 1,25-(OH)2D3 and the specific activities of kidney PAL and gamma-GT were decreased. The course of these effects was determined from 45 min to 8 h. In the presence of 1,25-(OH)2D3 (2 x 10(-6) M) a delayed (5h) but simultaneous stimulation of the three enzymes was observed. It reached a maximum at 6h and disappeared at 8h. The dose-response relation was studied at 6h. In the presence of 1,25-(OH)2D3 (5 x 10(-7) M), the three enzymes were activated. The effect was maximal at 10(-6) M; it was +22% for PAL, +17% and +15% respectively for gamma-GT and PAC compared with controls. Cycloheximide suppressed the induction of PAL but not of gamma-GT activity. The effects of the secosteroid on renal enzymes seems to be a pharmacological more than a physiological one.

Acid Phosphatase

[Urinary excretion of albumin and lipid abnormalities in hypertensive insulin-dependent diabetics].

Patients with insulin dependent diabetes mellitus (IDDM) often suffer from cardiovascular diseases as renal failure occurs. Elevated albumin excretion rate (AER) is a predictive value of this event. Relations between AER, blood pressure, serum lipids and apoproteins concentrations in 100 patients with IDDM have been surveyed. Twenty one hypertensive patients (HT group) were compared to 21 patients without hypertension (n HT group), matched for sex, age, diabetes duration, and metabolic control, assessed by glycosylated haemoglobin. Comparison of both groups showed HT group had elevated systolic blood pressure (137 +/- 12 vs 126 +/- 20 mmHg; p less than .05), elevated diastolic blood pressure (80 +/- 7 vs 71 +/- 8 mmHg; p less than .001), increase in AER (27 range 3-4023 vs 6 range 2-51 mg/day; p less than .001), slightly elevated serum creatinine (95 +/- 32 vs 78 +/- 15 mumol/l; p less than .05). In HT group, serum lipid composition showed: raise in total cholesterol (251 +/- 43 vs 221 +/- 41 mg/dl; p less than 0.5), elevated apoprotein B (130 +/- 30 vs 99 +/- 21 mg/dl; p less than .001) elevated apoprotein B/apoprotein A1 ratio (.91 +/- .32 vs .66 +/- .27; p less than .001), elevated triglycerides (157 +/- 53 vs 98 +/- 43 mg/dl; p less than .005) and elevated LDL-cholesterol (170 +/- 42 vs 143 +/- 33 mg/dl; p less than .05). Levels of apoprotein A1 and HDL-cholesterol were not significantly different. Body mass index, daily insulin requirement and tobacco usage were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Use of 6 serum pools in standardization of the determination of apolipoproteins AI and B in the human serum].

The proliferation of commercial immunoassays for the determination of apolipoproteins AI and B as parameters of risk for coronary heart disease and the discordance between the values obtained with the systems have made more urgent than ever the need for standardization of these assays. The authors report here the results of a collaborative study on the standardization of the values between the "Comité Française de Coordination des Recherches sur l'Athérosclérose et le Cholestérol (ARCOL)" and 13 Companies providing 15 different analytical systems. The results show that standardized measurements are not possible using a "consensus international standard" and that the major problem is related to the enormous variability of the analytical systems. In contrast, the present study demonstrates that six different serum pools containing increasing amounts of apolipoproteins AI and B can be used to generate a common reference curve which permits calibration of all immunoassays and standardization of results.

Apolipoprotein A-I

Reactivity of HDL subfractions towards lecithin-cholesterol acyltransferase. Modulation by their content in free cholesterol.

(1) Human HDL2 (d 1.070-1.125) and HDL3 (d 1.125-1.21) labelled with unesterified [14C]cholesterol, were incubated with a source of lecithin-cholesterol acyltransferase. For optimal activity, the reaction required the addition of albumin in excess, at least 3-times greater than the concentration of HDL-free cholesterol. Under such conditions, the reaction appeared saturable. HDL3 was found the most efficient substrate and the Vmax values expressed for 1.5 IU LCAT/ml and with an albumin/free cholesterol ratio of 3, were 8.3 nmol free cholesterol esterified/ml per h and 4.1 nmol/ml per h for HDL3 and HDL2, respectively. (2) HDL3 were modified in the presence of VLDL by inducing triacylglycerol lipolysis with a semipurified lipoprotein lipase from bovine milk. The newly formed HDL had gained free cholesterol and phospholipids, so that about 50% of these modified HDL, referred to as light-LIP-HDL3, were reisolated in the HDL2 density range. Light-LIP-HDL3 were enriched mostly in free cholesterol (+ 160%) and in phospholipid (+ 40%). Their reactivity towards LCAT was half-reduced compared to parent HDL3, which correlated well with a decrease in their phospholipid/free cholesterol molar ratio. Moreover, HDL3 artificially enriched in free cholesterol and exhibiting a comparable PL/FC behaved like lipolysis-modified HDL in their reactivity towards LCAT. (3) HDL3 were also modified by co-incubation with VLDL (post-VLDL-HDL3), or with VLDL and a source of lipid transfer protein (CET-HDL3). The latter treatment greatly affected the lipid composition of the core particle (-25% esterified cholesterol, +190% TG). In both cases, the moderate decreasing LCAT reactivity observed could be related to the phospholipid/free cholesterol ratio. Thus, like in artificial substrates, the lipid composition of the HDL surface may control the rate of LCAT-mediated cholesterol esterification.

Animals

[In vitro stimulation of alkaline phosphatase and gamma- glutamyltransferase in the kidney of hypophysectomized rat by the mixture of 1,25 and 24,25 dihydroxycholecalciferols].

The present study was undertaken to investigate the in vitro effects of two cholecalciferol metabolites 1,25(OH)2CC and 24,25(OH)2CC on the renal cortex alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) and acid phosphatase (ACP) activities in hypophysectomized rats. We found that both 1,25-CC and 24,25-CC stimulated ALP and GGT. An additive effect was obtained on ALP and GGT after incubation with one with the other metabolites. When 1,25-CC was used alone, it increased ACP; in presence of 24,25-CC, this stimulating effect disappeared. In the rat, together 1,25-CC and 24,25-CC correct in vitro ALP and GGT activities decreased by hypophysectomy. Physiological signification of these effects remains again unknown.

24,25-Dihydroxyvitamin D 3

Effects of keto-analogues on phosphocalcic and aminoacid metabolism in dialysed patients: a crossover study.

It has been suggested that calcium salts of keto-analogues (KA) have beneficial effects on phosphocalcic and aminoacid (AA) metabolism. To confirm this, their short-term effects were evaluated on chronic dialyzed patients. In a prospective, randomised, crossover study, eight and seven patients were put on KA (200 mg/kg/d) and assigned either a low-protein diet (LP:0.4 g/kg/d) or a normal one (NP: 1 g/kg/d) for 15 days. The two treatments were interchanged after 15 days of washout. KA.LP was accompanied by: a) decreases in calorie intake (12%; p = 0.001) and in blood concentrations of albumin (5%, p = 0.004), urea (32%, p = 0.001), phosphate (29%, p = 0.001), parathormone (27%, p = 0.008), isoleucine (24%, p = 0.04), 1 and 3 methyl-histidine (71%, p = 0.03; 24%, p = 0.005), valine (19%, p = 0.004) and hydroxyproline (85%, p = 0.009); b) increases in calcemia (9%, p = 0.002), cystathionine (991%, p = 0.0001) and threonine (22%, p = 0.04). KA.NP was accompanied by: a) decreases in phosphatemia (15%, p = 0.03) and parathormone (18%, p = 0.06); b) increases in calcemia (9%, p = 0.002), cystathionine (427%, p = 0.0001), and phenylalanine (28%, p = 0.013). Calcium salts of keto-analogues together with a low or normal protein diet thus seem to reduce blood concentrations of phosphates and parathormone, and raise calcium; however their action on aminoacids needs further investigation.

Aged