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Biomedical subjects

D Durand

Publications and source records attributed to D Durand.

At least 127 records · Page 7Linked to original sources
PubMed1997

Changes in blood pressure and renal function following subtotal parathyroidectomy in renal transplant patients presenting with persistent hypercalcemic hyperparathyroidism.

The aims of this retrospective study were to assess renal function and blood pressure after subtotal parathyroidectomy (PTx) performed in renal transplant (RT) patients presenting with persistent hypercalcemic hyperparathyroidism. We identified 34 patients (group A) from our records who had undergone PTx between 1981 and 1994. Group A included 18 women and 16 men with a mean age of 45 +/- 12 years and a mean time on dialysis therapy of 102 +/- 59 months. Thirty of the patients received cyclosporine A (CsA) with or without steroids and/or azathioprine (AZA) and the remaining 4 patients received conventional therapy i.e. AZA and steroids. Twenty-three patients were treated for hypertension and 11 were normotensive. PTx was performed in 21 patients within the first year following renal transplantation and in 13 patients after this period. The study was divided into 3 periods: period 1-pre-PTx; period 2-the month following PTx; period 3-six months after PTx. Parameters were assessed for every patient in each of these periods. Results of group A were compared to those observed in 34 matched (control) RT patients (group B) who did not experience secondary hyperparathyroidism. PTx was associated with a significant decrease in parathyroid hormone (PTH) levels (45 +/- 8 pg/ml vs 338 +/- 54 pg/ml; p = 0.0002) and in calcemia (2.32 +/- 0.18 mmol/l vs 2.75 +/- 0.15 mmol/l; p = 0.0003) during period 3. However, we observed a significant increase in serum creatinine (124 +/- 30 mumol/l vs 110 +/- 25 mumol/l, p = 0.0016) in this group during period 3. Nevertheless, an increase in serum creatinine greater than 30% from baseline which still persisted six months after PTx was only observed in 8 patients (23.5%). There were more hypertensive patients in this latter subgroup (7 out of 8 i.e. 87.5%) than in the rest of the group (16 out of 26 i.e. 64.5%). Renal function impairment in group A was not related to pre-PTx SBP, DBP, MBP, calcemia, creatinine, CsA whole blood trough levels or PTH levels. Conversely, we did not observe significant changes in serum creatinine in the control group during the same periods. During period 2 there was a significant decrease in SBP (134 +/- 16 vs 140 +/- 16 mmHg; p = 0.046), DBP (81 +/- 9 vs 85 +/- 9 mmHg; p = 0.03) and MBP (99.5 +/- 10.5 vs 103.5 +/- 11 mmHg; p = 0.03) of group A. These differences persisted in period 3, with the exception of SBP, although they were no longer statistically significant. Following PTx we were able to discontinue (n = 4) or decrease (n = 4) antihypertensive drugs. In the control group baseline SBP, DBP and MBP were lower than in the PTx group, although the difference was statistically significant only for SBP (132.5 +/- 17 vs 140.5 +/- 16 mmHg; p = 0.05). During the study periods there was no significant changes in SBP, DBP or MBP in the control group. This study shows that RT patients with hypercalcemic hyperparathyroidism are often hypertensive (68%). Subtotal PTx is associated with a significant but transient decrease in SBP, DBP and MBP. Surprisingly we observe a significant and persistent increase in serum creatinine levels in 8 patients (23.5%), particularly in those presenting with hypertension before PTx. These results could reflect a dual effect of parathyroid hormone i.e. a balance between a vasodilating and hypertensive effect.

Adult↗
PubMed1997

Picosecond dynamical changes on denaturation of yeast phosphoglycerate kinase revealed by quasielastic neutron scattering.

Quasielastic neutron scattering experiments performed on yeast phosphoglycerate kinase in the native form and denatured in 1.5 M guanidinium chloride reveal a change in the fast (picosecond time scale) diffusive internal dynamics of the protein. The momentum and energy transfer dependences of the scattering for both states are fitted by an analytical model in which, on the experimentally accessible picosecond time scale and angstrom length scale, the dynamics of a fraction of the nonexchangeable hydrogens in the protein is described as a superposition of vibrations with uniform diffusion in a sphere, the rest of the hydrogens undergoing only vibrational motion. The fraction diffusing changes, from approximately 60% in the native protein to approximately 82% in the denatured protein. The radius of the sphere also changes slightly, from approximately 1.8 A in the native protein to approximately 2.2 A in the denatured protein. Possible implications of these results for the general protein folding problem are discussed.

Guanidine↗
PubMed1997

[HCV RNA clearance after treatment with interferon-alpha in chronic hemodialysis patients with or without coinfection by HGV/HGBV-C].

Patients on maintenance hemodialysis are frequently infected with hepatitis C virus (HCV). The long-term effect of alpha interferon therapy has not yet been assessed, or the influence of co-infection with the newly discovered hepatitis G/hepatitis GB virus-C (HGV/HGBV-C) upon therapy outcome. Eleven anti-HCV and HCV RNA-positive hemodialysis patients, 3 of whom had HGV/HGBV-C infection were given 3 mega-units of alpha 2b recombinant interferon subcutaneously 3 times weekly for six months. The mean follow-up after cessation of therapy was 24 +/- 8 months (range: 18-30 months). Sustained serum HCV RNA clearance, as assessed by PCR analysis, occurred in 5/11 patients (45.5%). Two had received a cadaveric kidney transplant at 16 and 18 months post-treatment and were treated by immunosuppressive therapy; HCV RNA remained undetectable in both serum and a liver biopsy. HCV was eradicated in 3 of the 6 patients infected with HCV genotype 1b, which is less sensitive to alpha-interferon than other HCV genotypes. Among the 3 patients infected with both HCV and HGV/HGBV-C, alpha-interferon cleared the HCV RNA from one patient, but not the HGV/HGBV-C RNA. In view of the high rate of HCV eradication after alpha-interferon therapy and its fair tolerance, we suggest that HCV RNA-positive dialysis patients should be treated before transplantation, regardless of their aminotransferase levels or liver histological score, since alpha interferon therapy after renal allografting is associated with an unacceptable rate of renal failure. Our preliminary data indicate that HGV/HGBV-C does not interfere with sustained HCV RNA clearance.

Adult↗
PubMed1996

A randomized multicenter trial comparing leukocyte function-associated antigen-1 monoclonal antibody with rabbit antithymocyte globulin as induction treatment in first kidney transplantations.

Adhesion molecules are involved in several steps in the immune response: leukocyte adhesion to the endothelium, transendothelial migration, cooperation between immunocompetent cells, and cytotoxicity. Leukocyte function-associated antigen-1 plays a central role among adhesion molecules. In a multicenter randomized open trial, we compared a monoclonal antibody directed against the alpha chain of LFA-1 (Oduli-momab; IMTIX/Pasteur Mérieux Sérums et Vaccins) with rabbit antithymocyte globulin (rATG; IMTIX/Pasteur Mérieux Sérums et Vaccins), as part of a quadruple sequential protocol in 101 patients receiving a first kidney transplant. Clinical tolerance of anti-LFA-1 mAb was better than that of rATG. Short-term rejection rates (< 15 days) were not significantly different (15% and 16% for anti-LFA-1 mAb and rATG, respectively). However, 11% of the anti-LFA-1 mAb patients experienced rejection during the first 10 days of the treatment course compared with none of the patients treated with rATG. The incidence and severity of acute rejection in the first 3 months was not significantly different between groups. Of the LFA-1 and rATG patients, 96% and 92% of the grafts, respectively, were functioning at 12 months. The incidence and severity of infection, whatever the origin, were comparable in both groups. In addition, it was observed that fewer patients required posttransplantation dialysis in the anti-LFA-1 mAb group (19%, vs. 35% for rATG), although the difference was not statistically significant. Altogether, the beneficial action of this monoclonal antibody on short-term renal function recovery makes it a useful tool in the management of renal patients undergoing kidney transplantation.

Acute Disease↗
PubMed1996

Comparison of four methods for isolating large mRNA: apolipoprotein B mRNA in bovine and rat livers.

The effectiveness of four methods for isolating large-size mRNA (14 kb) encoding for hepatic bovine apoprotein B (apo B) was compared. Total RNA of liver (positive controls) and lung (negative controls) samples taken in bovine and rat was extracted using the methods of Chirgwin et al., Chomczynski and Sacchi, Cathala et al., and RNAzol. The integrity of total RNA extracted by the four methods was demonstrated by electrophoresis on 1% agarose gel and staining with ethidium bromide. Yield of extraction was two- to four-fold higher for all samples with the methods of Chirgwin et al. and RNAzol than that with the other methods. By dot blot analysis, apo B mRNA in bovine and rat livers was revealed preferentially with Chirgwin et al. and RNAzol methods. By Northern blot analysis, a single band corresponding to apo B100 mRNA was shown in bovine and rat livers only with the method of Chirgwin et al., whereas a band corresponding to a medium-size mRNA (2.6 kb) encoding for rat phosphoenolpyruvate carboxykinase was revealed in rat liver samples with the four methods. These results showed the favorable role of guanidium isothiocyanate and guanidium hydrochloride used in the extraction and the purification of RNA, respectively, especially in the case of high-molecular-weight and/or low-represented RNA such as apo B mRNA in bovine liver.

Animals↗
PubMed1996

The effect of temperature and ionic strength on the dimerisation of beta-lactoglobulin.

Bovine beta-lactoglobulin is a globular whey protein that associates partly and reversibly in dimers in the native state. Static and dynamic light scattering techniques have been used to determine the relative amount of monomers and dimers, and to estimate their size and shape in different conditions. The effect of the ionic strength on the dimerisation has been studied at pH 2, where the protein is highly charged. A simple model, taking into account the monomer-dimer equilibrium and virial interactions has been used. The strength of the interactions depends on the amount of added salt, i.e. ionic strength, and influences the dimer dissociation. When the ionic strength decreases, the equilibrium is shifted towards the monomeric form. The dissociation, however, is only complete at very low concentration. The effect of temperature has been studied at pH 7 and low concentration where virial interactions are negligible. The dissociation increases with increasing temperature (5 degrees C - 76 degrees C). At high temperatures, protein-protein aggregation is fast, even at low concentration. The temperature dependence can be described using a simple Van't Hoff model, even at temperatures where aggregation occurs. The ionic strength and temperature dependence both indicate that beta-lactoglobulin solutions have to be considered as a mixture of monomers and dimers.

Hydrogen-Ion Concentration↗
PubMed1996

DNA mesophases induced by spermidine: structural properties and biological implications.

Conditions of formation of DNA aggregates by the addition of spermidine were determined with 146 base pair DNA fragments as a function of spermidine and NaCl concentration. Two different phases of spermidine-DNA complexes are obtained: a cholesteric liquid crystalline phase with a large helical pitch, with interhelix distances ranging from 31.6 to 32.6 A, and a columnar hexagonal phase with a restricted fluidity in which DNA molecules are more closely packed (29.85 +/- 0.05 A). In both phases, the DNA molecule retains its B form. These phases are always observed in equilibrium with the dilute isotropic solution, and their phase diagram is defined for a DNA concentration of 1 mg/ml. DNA liquid crystalline phases induced by spermidine are compared with the DNA mesophases already described in concentrated solutions in the absence of spermidine. We propose that the liquid crystalline character of the spermidine DNA complexes is involved in the stimulation of the functional properties of the DNA reported in numerous experimental articles, and we discuss how the nature of the phase could regulate the degree of activity of the molecule.

Animals↗
PubMed1996

1 alpha,25-dihydroxyvitamin D3 stimulated alkaline phosphatase activity in cultured pig kidney epithelial LLC-PK1 cells.

The effects of 1 alpha,25-dihydroxyvitamin D3 (1,25 (OH)2D3) and human growth hormone (hGH) on the activity of alkaline phosphatase (ALP) were evaluated in pig kidney LLC-PK1 cultured cells. 1,25(OH)2D3 (10(-9)-10(-6) mol L-1) and hGH (10(-7) mol L-1) increased ALP activity in these cells while no hormonal effect was detected on two other enzyme activities: gamma-glutamyl transferase and acid phosphatase. ALP activity was maximally increased after 4.5-6 h incubation with both hormones. The hormonal induction of ALP activity was prevented by a pretreatment of cells with actinomycin D. Thus, 1,25 (OH)2D3 and may be hGH could stimulate ALP activity via a transcription of some gene.

Acid Phosphatase↗
PubMed1996

Regulation of VLDL synthesis and secretion in the liver.

The production of very low density lipoproteins (VLDL) by the liver results from very complex processes that involve coordinated mechanisms of both protein and lipid synthesis and packaging. Alterations in these metabolic functions can cause negative effects on the health of human subjects or animals. The objectives of this paper were to review the latest developments in the biological mechanisms of these processes and the role of nutritional and hormonal factors. The present study addresses the following issues: i) the main steps in the hepatic metabolism of lipids (long-chain fatty acids, triacylglycerols, phospholipids) and proteins (apolipoprotein B, microsomal transfer protein) primarily involved in the synthesis and secretion of VLDL particles; ii) the metabolic deviations of hepatic VLDL (hypo- and overproduction) in man, rodents and farm animals (poultry, dairy cows).

Animals↗
PubMed1996

Epidemiology of HCV infection: disease and renal transplantation.

We studied the prevalence of HCV infection in a cohort of 346 patients who received renal transplantation between January 1989 and April 1994. Assessments were made at the time of surgery, one year later and at the last follow-up visit. The hepatic consequences of HCV infection were also studied. The prevalence of HCV infection at the time of surgery was 21.4% (74/346). The risk factors associated with the presence of anti-HCV antibodies were: duration of haemodialysis, the number of transfusions and the number of previous renal transplantations. The incidence of HCV infection was 3% (8/272) and was accompanied by either transient (n = 4) or chronic (n = 3) hepatic cytolysis; five patients underwent liver biopsy which revealed persistent chronic hepatitis (n = 2) or active chronic hepatitis (n = 3). Seroconversion always occurred within one year following transplantation. In the long-term, 91% of HCV+ patients remained viraemic. The HCV genotype was predominantly 1b. Fifty-six per cent (56%) of HCV+ patients had normal ALAT at the time of transplantation, which remained normal on follow-up in two-thirds of cases. After transplantation, 39 HCV+ patients underwent liver biopsy. ALAT were normal in 13 of those; liver biopsy elicited either normal liver (n = 1) or chronic persistent hepatitis (CPH) (n = 8) or chronic active hepatitis (CAH) (n = 4). ALAT were chronically elevated in 26 patients; liver histology revealed: 7 CPH, 19 CAH including 12 cases with bridging fibrosis. No deleterious effect of azathioprine on liver histology was found. Lastly, four patients were co-infected with HBV: all had elevated ALAT; liver biopsy always revealed severe chronic active hepatitis. Post-transplantation hepatitis C is a worrying problem. Liver enzymes are not correlated with the severity of histological disorders, which are frequent. Interferon-alpha therapy should be proposed to HCV+ patients before renal transplantation.

Adult↗
PubMed1996

Serological markers of autoimmunity in renal transplant patients before and after alpha-interferon therapy for chronic hepatitis C.

Chronic hepatitis C is the major cause of chronic liver disease after successful cadaveric renal transplantation. The aims of this prospective, open study were to assess in such a population, firstly the prevalence of different organ-specific and nonspecific antibodies and related disorders, and secondly their outcome after inteferon-alpha therapy as well as the incidence of new immunologic disorders under and after this therapy. In 15 cadaveric renal transplant patients (10 men, 5 women, ages 29-65 years) with chronic hepatitis C and histological features of chronic active hepatitis, undergoing chronic immunosuppression (ciclosporine A with or without steroid and azathioprine) and treated with recombinant alpha 2b-interferon (IFN alpha) (mean duration 142 +/- 35 days), we assessed before and after this therapy the serum levels of cryoglobulinemia, rheumatoid factors (RF), thyroid-stimulating hormone (TSH), free thyroxine (fT4), and antinuclear (ANA), antismooth muscle (ASMA), antimitochondrial (AMA), anti-LKM1, antimicrosomal thyroid (MCA), antithyroglobulin (TGA) autoantibodies. At the start of IFN alpha therapy, 14 of 15 patients had detectable autoantibodies (RF: 9; ANA > 1/50: 8; ASMA > 1/50: 4; other autoantibodies: 0); 1 had cryoglobulinemia. At the end of therapy the cryoglobulinemia had disappeared, the preexisting autoantibodies remained present in all patients but 2; 3 patients had developed MCA without evidence of clinical or biological thyroid abnormalities and 3 others had developed either RF (1) or ANA (1) or ASMA (1), without any related symptoms. One patient developed transient type II diabetes mellitus without anti-Langerhans beta-cell antibodies. Finally, the occurrence of autoantibodies in our patients was associated either with HLA DR3 or DR4 or DR7 phenotypes. We found that the prevalence of extrahepatic immunologic abnormalities was high in renal transplant patients with chronic hepatitis C and no exacerbation was observed during of after IFN alpha therapy. The most frequent autoantibody appearing after IFN alpha therapy was MCA although without thyroid abnormalities.

Adult↗
PubMed1996

Acute renal failure in kidney transplant patients treated with interferon alpha 2b for chronic hepatitis C.

Sixteen kidney transplant (KT) patients (10 men, 6 women, aged 49 +/- 10 years) with chronic hepatitis C alpha-interferon (IFN-alpha) therapy (Intron A, Schering Plough) at a dose of 3 x 10(6) units subcutaneously 3 times a week. The treatment was scheduled for 24 consecutive weeks. Each patient had had stable renal function for at least 12 months prior to IFN-alpha therapy (mean serum creatinine, SCr, 121 +/- 38 mmol/l). Fourteen patients were receiving cyclosporin-A (CsA)-based immunosuppression and 2 patients were on conventional therapy. The patients' SCr was checked every 2 weeks while on IFN-alpha, or weekly if it increased more than 15% from baseline. IFN-alpha was withdrawn if SCr increased more than 25% from baseline, in which case a kidney biopsy was performed. Six patients experienced either acute (n = 5) or subacute (n = 1) renal failure within 7-24 weeks after the onset of IFN-alpha therapy. Their mean SCr increased from 105 +/- 31 to 207 +/- 63 mmol/l (p = 0.02) with de novo proteinuria in 1 case (1 g/day) and an increase in preexisting proteinuria in 2. The other 3 patients did not develop proteinuria. In each case, histological study showed diffuse interstitial edema associated with dilation of the peritubular capillaries, whereas mild inflammatory infiltrates were present in only 3 cases and mild glomerular lesions were not always found (glomerular ischemia, mesangial hypertrophy). There were no vascular lesions. IFN-alpha was withdrawn in these 6 patients, in association with methylprednisolone pulses in 5 cases. Renal function improved in 2 cases, stabilized in 1 and progressed to end-stage renal failure in 3 within 4-12 months. Four of these patients had iterative renal biopsies which showed diffuse interstitial fibrosis in each case. The patients who developed renal failure did not statistically differ at the start of the study from those who did not, with respect to the following: baseline immunosuppression, HLA matching, total peripheral blood lymphocyte count or peripheral blood lymphocyte subtypes. IFN-alpha therapy was associated with acute or subacute renal failure in 37% of the patients. The most prominent histological finding was diffuse interstitial edema of rapid onset, without signs of cellular or vascular rejection. In conclusion, we do not recommend IFN-alpha therapy for KT patients with chronic hepatitis C, until the mechanisms of the subsequent renal failure are better understood.

Acute Kidney Injury↗
PubMed1996

Renal functional reserve in kidney and heart transplant recipients.

Renal functional impairment paradoxically often seems less severe in kidney than in heart-transplant recipients (KTR and HTR, respectively) when both are submitted to cyclosporine therapy. Renal functional reserve (RFR), elicited by a 3-h intravenous amino acid infusion, was examined in 12 KTR and 13 HTR at 7 to 8 months, appropriately compared with either eight one-kidney or 12 two-kidney healthy control subjects (1K.C and 2K.C, respectively). Baseline GFR was 54 +/- 4 mL/min in KTR and 71 +/- 4 mL/min in HTR (P < 0.05). During amino acid infusion, the maximum increase in GFR (which represented RFR) was 17 +/- 3 mL/min in both KTR and HTR (P < 0.001). RFR in KTR was 96 +/- 18% of that in 1K.C, whereas RFR in HTR was only 59 +/- 9% of that in 2K.C. Effective RPF increased (41 +/- 8 mL/min, P < 0.001), and renal vascular resistances decreased (48 +/- 17 mm Hg/L per min, P < 0.05) in KTR but not in HTR. These results demonstrate that both KTR and HTR possess a renal reserve but that the single renal graft in KTR retains a proportionally higher baseline GFR and a better ability to exhibit a RFR than the two native kidneys in HTR. This dissimilar impairment could result from slightly higher cyclosporine dosage, activation of the intact renal sympathetic innervation accentuated by cardiac denervation, renal consequences of former heart failure and potential alterations in the cardiac graft function, and/or higher prevalence of hypertension and additive therapies in HTR.

Adult↗
PubMed1996

Circadian changes in net nutrient fluxes across the portal-drained viscera, the liver, and the hindquarters in preruminant calves.

The objective of this study was to describe in preruminant calves the circadian patterns in net nutrient fluxes across the portal-drained viscera, the liver, and the hindquarters and to relate them to previously published variations in tissue energy expenditure. In vivo arterio-venous techniques were used, and animals were fed a conventional milk replacer. In the portal-drained viscera, net glucose absorption occurred 1 to 5 h postprandially with some lactate release. Arterial plasma non-esterified fatty acid (NEFA) concentrations decreased subsequently, as well as net NEFA uptake by the portal-drained viscera. Triglyceride absorption that occurred 1 as well as 7 or 8 h postprandially did not take place via the portal vein. Changes in energy expenditure of the portal-drained viscera did not correlate with changes in net nutrient fluxes. In the liver, the maximum contribution of lactate to hepatic glucose production was 20%. The NEFA and triglycerides were taken up by the liver, whereas urea was released. Only increases in NEFA uptake could partly explain the postprandial rise in hepatic energy expenditure. In the hindquarters, up to 48% of the glucose taken up could be converted into lactate; the remaining balance was possibly oxidized, thereby contributing as much as 33% to energy expenditure. No hourly patterns were noted in net nutrient fluxes through hindquarters. In conclusion, in preruminants, contribution of nutrients to oxidation differed from that noted in ruminants and seemed to vary with nutrient absorption and availability patterns, especially in the portal-drained viscera.

Aging↗
PubMed1996

Treatment of chronic hepatitis B and C with alpha interferon in a renal transplant patient.

We report the case of a 51-year-old renal transplant patient, treated by interferon alpha (5MUI, three times a week) since he presented a coinfection by hepatitis B (HBV) and hepatitis C (HCV) virus for more than 7 years, associated with a chronic increase in serum alanine aminotransferase (ALT) levels and a chronic active hepatitis. The 4-month treatment was associated with a sustained normalization of ALT, a disappearance of HBV replication and a transient clearance of HCV viremia. Side effects were moderate and included thrombopenia (90,000/mm3), leucopenia (2200/mm3), an increase in serum creatinine (178 mumol/l). The withdrawal of alpha interferon was associated with the correction of these parameters. No rejection was observed on kidney biopsy. Meanwhile, liver histology was not affected by the treatment. To date, nineteen months after the end of alpha interferon therapy HBV DNA was still negative; ALT remained normal despite the early recurrence of HCV viremia; this emphasized the fact that HBV infection was certainly the most important factor involved in the patient's chronic hepatitis. It is concluded that alpha interferon therapy is able to decline HBV replication for a prolonged period in renal transplant patient although its use should be performed with caution due to the potential renal side effects.

Dose-Response Relationship, Drug↗