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Biomedical subjects

D Durand

Publications and source records attributed to D Durand.

At least 109 records · Page 6Linked to original sources

Pharmacokinetics of alphaIFN-2b in chronic hepatitis C virus patients undergoing chronic hemodialysis or with normal renal function: clinical implications.

In this prospective controlled study, the pharmacokinetic profiles of alpha-interferon 2b (alphaIFN-2b) were determined by the enzyme-linked immunosorbent assay method in hepatitis C virus-positive (HCV+) dialysis and nonuremic patients, after a single subcutaneous injection of 3 million units. Ten HCV+/RNA+ patients (group A) with a normal renal function (mean serum creatinine: 1.03 +/- 0.26 [SD] mg/dl) and 10 HCV+/RNA+ patients undergoing chronic hemodialysis (group B) were included. The pharmacokinetic profiles of alphaIFN were determined after the very first subcutaneous injection of the drug. Plasma alphaIFN concentrations were determined before the injection and then 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, and 36 h after the injection. They were assessed by means of an enzyme-linked immunosorbent assay test. Patients from both groups had a similar body surface area. It was found that in group B: (1) the mean maximum (SD) serum alphaIFN concentration (Cmax) was significantly higher (52 +/- 12 pg/ml) than in group A (39 +/- 12 pg/ml; P = 0.03); (2) the time at which Cmax occurred (Tmax) was significantly higher (10 +/- 3 h) than in group A (7.5 +/- 2 h; P = 0.05); (3) the observed area under the plasma alphaIFN concentration-time curve was about twice as much, i.e., 936 +/- 212 pg x h/ml, as that for group A (485 +/- 184 pg x h/ml; P < 0.0001); and (4) the alphaIFN half-life was significantly longer (9.6 +/- 2.9 h) than in group A (5.3 +/- 1.3 h). As early as 24 h after the alphaIFN injection was given, the drug was no longer detectable in nonuremic patients' sera, whereas it could be detected up to the next injection in all of the dialysis patients' sera. When trough levels of alphaIFN were measured just before the 10th injection, they were always below the threshold level in the 10 patients from group A, i.e., 4.1 pg/ml, whereas in group B they were measurable for four of nine patients (P = 0.05) and ranged between 5.8 and 36.1 pg/ml. Severe neurologic side effects were observed only in group B, i.e., in three patients. Hemoglobin levels did significantly decrease but only in group B patients, and this was significantly correlated with the Cmax (r = 0.67; P = 0.03). This is the first controlled study to demonstrate that the clearance of alphaIFN is about twice as low in dialysis patients as in nonuremic patients. These results might be of relevance when deciding the optimal alphaIFN therapy scheme for HCV+ patients, either with normal renal function or undergoing chronic hemodialysis.

Adult↗

Psychological health and trauma in male and female soldiers.

This study assessed the effect of premilitary and military trauma on the psychological health of more than 1,000 female and male active duty soldiers. Questionnaire data provided information on demographics, history of trauma exposure, and general psychological health as assessed by the Brief Symptom Inventory (BSI). The results indicated that females reported experiencing more sexual traumas and males reported more nonsexual traumas. BSI subscale scores indicated poorer psychological health among all of the subjects compared with BSI normative groups and other Army soldiers. The need for military norms for the BSI is discussed.

Adult↗

Effects of premilitary and military trauma on the development of post-traumatic stress disorder symptoms in female and male active duty soldiers.

We surveyed more than 1,000 female and male active duty soldiers to assess the effect of premilitary and military trauma on their psychological well-being. Questionnaire data were obtained on pertinent demographic information, history of trauma exposure, and symptoms of post-traumatic stress disorder (PTSD). The results indicated significant gender differences in the types of traumatic events experienced, with females reporting more sexual traumas and males reporting more nonsexual traumas. In addition, males reported experiencing more military-related traumas, whereas females reported experiencing more premilitary traumas. The prevalence of PTSD symptoms was 8.6% for females and 5% for males. Recommendations are presented that may help mitigate development of PTSD symptoms in the future.

Adult↗

Opioid withdrawal in neonates after continuous infusions of morphine or fentanyl during extracorporeal membrane oxygenation.

BACKGROUND: Complications of opioid analgesia include tolerance and withdrawal. OBJECTIVES: To determine the effects of morphine and fentanyl on the prevalence of withdrawal after extracorporeal membrane oxygenation. METHODS: Two groups of neonates were compared during and after extracorporeal membrane oxygenation: a prospective group receiving a continuous infusion of morphine for analgesia and sedation and a retrospective group who had received a continuous infusion of fentanyl. RESULTS: Neonates receiving morphine required significantly less supplemental analgesia (P < .001) than did neonates who had received fentanyl and had a significantly lower prevalence of withdrawal after the therapy (P = .01). Neonates receiving morphine were discharged from the hospital a mean of 9.6 days sooner (P = .01) than neonates who had received fentanyl. CONCLUSIONS: Morphine may offer marked advantages over fentanyl for providing continuous analgesia and sedation in neonates.

Analgesics, Opioid↗

Efficacy and safety of lamivudine on replication of recurrent hepatitis B after cadaveric renal transplantation.

BACKGROUND: The aim of this pilot study was to evaluate the efficacy and the safety of lamivudine therapy in hepatitis B virus (HBV)-positive/DNA-positive renal transplant recipients. METHODS: Six HBV DNA-positive cadaveric renal transplant recipients ranging in age from 49+/-6 years were administered lamivudine, at 100 mg/day for a period of at least 6 months, on a compassionate-use basis. Lamivudine is the (-) enantiomer of 3'-thiacytidine, which is known to be a potent inhibitor of HBV replication. All of the patients but one were on cyclosporine-based immunosuppression. RESULTS: The mean serum creatinine was 134+/-44 micromol/L. The mean duration of HBV infection was 230+/-54 months (156-288). All of the patients but one had high serum alanine aminotransferase levels (122+/-52 IU/L; range, 45-243). Histological evaluation showed the presence of either chronic active hepatitis (n=4) or cirrhosis (n=2). All of the patients but one were hepatitis B e antigen negative/hepatitis B e antibody positive, but none were coinfected with either hepatitis C virus or hepatitis D virus. CONCLUSIONS: Lamivudine therapy was associated with (i) a normalization of alanine aminotransferase levels in four of five patients when these levels were increased at the beginning (n=5); (ii) a rapid disappearance of HBV DNA from the serum (detected by hybridization) in all of the patients; (iii) the negativity of HBV DNA by polymerase chain reaction in four patients; and (iv) no change in renal function and in proteinuria when present (one patient). Finally, no adverse effects were noted. When lamivudine therapy was stopped for four patients after 6 months, it was associated with a biochemical and virological relapse within the weeks that followed. Lamivudine therapy was therefore resumed for these patients.

Antiviral Agents↗

[Preparation for transplantation and graft patient management].

Often considered at the end of a long standing chronic disease, organ transplantation requires a preparation and a strict follow up before grafting which are centered upon the prevention of the risks related to the waiting of the graft and the assessment of the risk related to the transplantation itself. Follow up of the patient after transplantation cannot be interrupted. It is a multidisciplinary approach which is focused primarily upon the function of the graft, the tolerance to immunosuppressive drugs, the detection and prevention of their complications.

Follow-Up Studies↗

Small-angle neutron scattering by a strongly denatured protein: analysis using random polymer theory.

Small-angle neutron scattering profiles are presented from phosphoglycerate kinase, in the native form and strongly denatured in 4 M guanidinium chloride (GdnHCl) solution. The data are interpreted using a model in which the excess scattering density associated with the protein is represented as a finite freely jointed chain of spheres. The similarity of the model-derived scattering function to experiment increases asymptotically with the number of spheres. The improvement of the fit obtained with more than approximately 200 spheres (i.e., two residues per sphere) is insignificant. The effects of finite size of the scattering units and of scattering length variation along the polypeptide chain are examined. Improved agreement with experiment is obtained when these effects are taken into account. A method for rapid calculation of the scattering profile of a full, all-atom configuration is examined. It is found that a representation of the chain containing two scattering units per residue, placed at the backbone and side-chain scattering length centroids, reproduces the full, all-atom profile to within 2%.

Fourier Analysis↗

Outcome of patients with antineutrophil cytoplasmic autoantibody-associated vasculitis following cadaveric kidney transplantation.

In this retrospective study, we report on the progress of eight patients with biopsy-proven systemic vasculitis following cadaveric renal transplantation. Extrarenal manifestations associated with antineutrophil cytoplasmic autoantibodies (ANCAs) were present in all but one case. All the patients were on cyclosporine A-based immunosuppression, and none of them had active disease at transplantation. The mean time from the last episode of vasculitis to transplantation was 46 months (range, 10 to 132 months). On the day of transplantation, all but one patient had detectable ANCAs, which ranged from 1:100 to 1:2,000 (perinuclear ANCAs [P-ANCAs], four patients; cytoplasmic ANCAs [C-ANCAs], three patients). There were three patients with Wegener's granulomatosis, none of whom relapsed. Of those patients with microscopic polyangiitis (P-ANCAs, three patients; C-ANCAs, two patients), only one presented with relapse episodes after transplantation; the episodes involved the lungs and the kidney graft, and were successfully treated by methylprednisolone pulses. This patient had the highest ANCA titer before (1:2,000) and after (up to 1:10,000) grafting, and received no immunosuppression prior to transplantation since vasculitis was diagnosed after she had developed end-stage renal failure. This study shows that a relapse of ANCA-associated vasculitis following successful cadaveric renal transplantation occurs infrequently in the cyclosporine A era (ie, 12%), despite the persistence of circulating ANCAs in these patients at the time of transplantation, and even afterward in some cases.

Adult↗

High rate of hepatitis C virus clearance in hemodialysis patients after interferon-alpha therapy.

To gain insight into the long-term effect of interferon-alpha (IFN-alpha) therapy on hepatitis C virus (HCV) RNA-positive hemodialysis patients, 23 subjects were given 3 MU of IFN-alpha 3 times a week for 6 (n = 12) or 12 months (n = 11). They were followed for 19 months after cessation of therapy. Sustained serum HCV RNA clearance occurred in 42% of patients treated for 6 months and in 64% of those treated for 12 months. HCV was eradicated from 6 of 13 patients infected with HCV genotype 1b and from 2 of 6 patients also infected with hepatitis G virus. HCV RNA remained undetectable in both serum and a liver biopsy of 2 patients who were given cadaveric kidney transplants after IFN-alpha treatment. These data suggest that HCV RNA-positive dialysis patients can be considered for treatment while receiving dialysis, particularly those awaiting transplant.

Adult↗

Impact of migration and fitness on the stability of lethal t-haplotype polymorphism in Mus musculus: a computer study.

The t-haplotype is a chromosomal region in Mus musculus characterized by meiotic drive such that heterozygous males transmit t-bearing chromosomes to roughly 90% of their offspring. Most naturally occurring t-haplotypes express a recessive embryonic lethality, preventing fixation of the t-haplotype. Surprisingly, the t-haplotype occurs in nature as a persistent, low-frequency polymorphism. Early modeling studies led LEWONTIN to hypothesize that this low level polymorphism results from a balance between genetic drift in small demes and interdemic migration. Here, we show that while combination of deme size and migration rate that predict natural t-haplotype frequencies exist, the range of such values is too narrow to be biologically plausible, suggesting that small deme size and interdemic migration alone do not explain the observed t-haplotype frequencies. In response, we tested other factors that might explain the observed t-polymorphism. Two led to biologically plausible models: substantially reduced heterozygous fitness and reduced meiotic drive. This raises the question whether these phenomena occur in nature. Our data suggest an alternative explanation: there is no stable, low-level t-polymorphism. Rather wild populations are in one of two stable states characterized by extinction of the t-haplotype and a high t-haplotype frequency, respectively, or in transition between the two.

Alleles↗

The role of menopause in the development of chronic mountain sickness.

The objective of this study was to investigate the role of menopause in the appearance of the physiopathological sequence that leads to chronic mountain sickness (CMS) in a high-altitude female population. The females studied are 30-54 yr old (n = 152) and have permanent residence in Cerro de Pasco (Pasco, Peru; 4,300 m). The sample was divided into postmenopausal and premenopausal groups for comparison. Blood oxygen saturation (SaO2), excessive erythrocytosis [EE, measured by the level of hematocrit (Het)], peak expiratory flow rates (PEFR), and a score that represents the main signs and symptoms of CMS (CMSscore) were measured. Postmenopausal women had higher Het (50.2 +/- 4.04 vs. 47.4 +/- 4.13%, P < 0.001), lower SaO2 (81.9 +/- 4.12 vs. 84.7 +/- 3.14%, P < 0.001) and PEFR values (489 +/- 101 vs. 534 +/- 90 l/min, P < 0.02), and slightly higher CMSscore (19.1 +/- 3.37 vs. 17.9 +/- 3.48, P < 0.06) than premenopausal women. The prevalence of women with EE (EE = Hct > 56%) was found to be 8.8%. Forty-five percent of the postmenopausal subjects presented a high CMSscore (> 21), whereas only 22% of the premenopausal subjects presented this high value (P < 0.02). We can therefore conclude that menopause may represent a contributing factor for the development of CMS.

Adult↗

Prevalence of antibodies to hepatitis C virus and correlation with liver disease in renal transplant patients.

We studied the prevalence of hepatitis C virus (HCV) infection in 350 renal transplant (RT) patients with a functioning graft. The determination of HCV infection was based upon second-generation ELISA tests (ELISA-2, Abbott) confirmed by second-generation RIBA tests (RIBA-2, Chiron), including the proteins C22-3, C100-3, C33-C and 5-11. Three hundred and sixteen of these RT patients were on ciclosporin A (CsA) therapy with or without steroids (CS) and azathioprine (AZA); 34 received conventional immunosuppression. Eighty-seven RT patients were found to be HCV-positive (2.5%) when assessed by ELISA-2 tests; RIBA-2 was positive in 61 cases and 'indeterminate' in 26. Most of the HCV-positive patients had antibodies against C22-3 (94%), whereas antibodies against nonstructural antigens (C100-3, C33-C) were observed in 18 and 70% of cases, respectively. More than 88% of the HCV-positive patients were already HCV-positive before renal transplantation. Risk factors of developing HCV infection included: (i) the time on dialysis; (ii) the number of blood transufsions before transplantation, and (iii) the number of previous graft(s). There were significantly more HCV-positive patients among those on conventional immunosuppressive therapy (16 of 39) than among those on CsA (71 of 311; p < 0.02). Of those who where HCV-positive before transplantation, and for whom liver enzyme (LE) results were available (n = 68), 40 had either a normal or a transient increase in alanine aminotransferase (ALT) levels at that time, whereas 28 had a chronic increase in serum ALT +/- gamma-glutamyltranspeptidase levels. After transplantation, there was biochemical evidence of chronic liver disease in 33 patients (48.5%). Interestingly, 41 and 64% of those with respectively normal and increased LEs before transplantation presented with a biochemical chronic liver disease after RT. Surprisingly, 36% of those with a pretransplantation increase in ALT had normalized aminotransferase after transplantation. The daily doses of AZA, CS (i.e. prednisolone) were not statistically different between HCV-positive RT patients on conventional therapy (group A) and those on CsA (group B). Moreover, within each group, the daily doses of AZA, CS or CsA were not statistically different between those with a chronic increase in LEs and those with normal LEs. The percentage of HCV-positive RT patients with chronic abnormal LEs was not different between groups A and B. Surprisingly, the patients who were treated at least once for acute rejection with methylprednisolone pulses had a significantly lower incidence of chronic increases in LEs. Nine patients seroconverted for HCV after transplantation: 6 experienced a chronic increase in LEs. Finally, 7 of 87 patients were coinfected by HBV, all of them had a chronic increase in LEs. These results emphasize the fact that ALT alone cannot be used as a surrogate marker for chronic HCV infection in transplantation patients, thus a liver biopsy is required before and a few years after RT to assess liver damage in this population.

Adult↗

Kinetics of HCV viremia in kidney transplant recipients during and after alpha-interferon therapy.

Fifteen kidney transplant recipients with chronic hepatitis C were given 3 million units recombinant alpha2b-interferon for 142+/-35 days. There were significant decreases in hepatitis C virus (HCV) RNA 1 month after the initiation of treatment (p < 0.01), and at the end of treatment (p < 0.05). HCV RNA was undetectable by PCR analysis during treatment in 5 patients. But HCV RNA reappeared in all patients 1 month after the cessation of therapy, and the level of viremia returned to baseline. While all patients had normalized alanine aminotransferase (ALT) activities at the end of therapy, 11 experienced a relapse during the follow-up period (1 year). There was a correlation between the amount of HCV RNA at the end of treatment and the time of relapse. Serum IgM against core protein of HCV were detected in 7/15 patients. Anti-core IgM remained detectable during treatment and afterwards. There was no correlation between IgM status and other virological parameters, or ALT activity.

Adult↗

CMV prophylaxis in high-risk renal transplant patients (D+/R-) by acyclovir with or without hyperimmune (CMV) immunoglobulins: a prospective study.

In this prospective randomized study including 28 patients, we show that, in cytomegalovirus (CMV)-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+), high doses of acyclovir (ACV, i.e. 3,200 mg/day) during the first 3 months after transplantation were as efficient as hyperimmune CMV immunoglobulins (CMV Igs) plus high doses of ACV regarding the prophylaxis of CMV primoinfection. Fifty-four percent of the patients in the ACV arm and 50% in the other arm presented at least one episode of viremia (n.s.). The incidence of CMV disease was 31% in the ACV group and 20% in the ACV + CMV Ig group (n.s.). By comparison with historical controls (no prophylaxis), we found that ACV with or without CMV Ig significantly delayed and significantly decreased the rate of CMV disease, although the severity score was not statistically different. Moreover, high doses of ACV were far less expensive than their combination with hyperimmune CMV Igs. Thus, until oral ganciclovir is available for the prophylaxis of primary CMV infection in renal transplant patients, we recommend the use of high doses of ACV for the first 3 months after transplantation in high-risk renal transplant patients, i.e. D+/R-.

Acyclovir↗

Metastatic pulmonary calcification after renal transplantation.

Metastatic pulmonary calcifications, unlike dystrophic calcifications, occur in the normal healthy lung. The radiological pattern is quite specific. The disease is commonly described in chronic renal failure with calcium disorders. The prognosis is totally unpredictable. In 1992, a 50 yr old man underwent a successful renal transplantation during the final stage of chronic renal failure. He subsequently developed asymptomatic diffuse nodular opacities, that were discovered in 1995. An open lung biopsy confirmed the diagnosis of metastatic pulmonary calcification. There was no calcium disorder in this patient. In contrast to the benign course of pulmonary calcification in most patients, some fulminant pulmonary calcifications complicating renal transplantation or hypercalcaemia have been described. Radiographic identification of such entities is important to permit correction of calcium disorders. Otherwise, the condition is a potentially progressive and fatal cause of respiratory failure.

Calcinosis↗

Hepatic gene expression of apolipoprotein B100 during early lactation in underfed, high producing dairy cows.

The hepatic gene expression of apolipoprotein B, the major protein of very low density lipoproteins in plasma, was studied using 8 Holstein x Friesian cows during the first 12 wk of lactation. Cows were fattened during gestation and were underfed just after parturition to increase fat mobilization and subsequent hepatic steatosis. Intracellular concentrations of apolipoprotein B and apolipoprotein B mRNA and control parameters (albumin, total lipids, RNA, and proteins) were determined in liver samples obtained by biopsy from each cow on four occasions at 1, 2, 4, and 12 wk after calving. Results were compared with those obtained from 5 dry cows in late pregnancy and 4 dry nonpregnant cows. The hepatic concentration of apolipoprotein B was lower (approximately 25%) during wk 1, 2, and 4 after calving, a period of intense liver steatosis (44.2 to 95.7 mg of triglycerides/g of fresh tissue), than for nonsteatotic dry cows (pregnant or nonpregnant); hepatic concentrations were also lower than those during wk 12. In contrast, hepatic concentrations of mRNA coding for apolipoprotein B, total proteins, RNA, and albumin did not vary significantly during early lactation. These results suggested that synthesis of apolipoprotein B during early lactation is specifically regulated at a posttranscriptional level by a decrease in the rate of translation, or by a higher rate of intracellular degradation of apolipoprotein B, or both.

Albumins↗