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Biomedical subjects

L Perrin

Publications and source records attributed to L Perrin.

At least 73 records · Page 4Linked to original sources
PubMed1998

Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen.

We investigated CD4+ and CD8+ T cell turnover in both healthy and HIV-1-infected adults by measuring the nuclear antigen Ki-67 specific for cell proliferation. The mean growth fraction, corresponding to the expression of Ki-67, was 1.1% for CD4(+) T cells and 1.0% in CD8(+) T cells in healthy adults, and 6.5 and 4.3% in HIV-1-infected individuals, respectively. Analysis of CD45RA+ and CD45RO+ T cell subsets revealed a selective expansion of the CD8+ CD45RO+ subset in HIV-1-positive individuals. On the basis of the growth fraction, we derived the potential doubling time and the daily turnover of CD4+ and CD8+ T cells. In HIV-1-infected individuals, the mean potential doubling time of T cells was five times shorter than that of healthy adults. The mean daily turnover of CD4+ and CD8+ T cells in HIV-1-infected individuals was increased 2- and 6-fold, respectively, with more than 40-fold interindividual variation. In patients with <200 CD4+ counts, CD4+ turnover dropped markedly, whereas CD8+ turnover remained elevated. The large variations in CD4+ T cell turnover might be relevant to individual differences in disease progression.

Adult↗
PubMed1998

Transforming laboratory test results to improve clinical outcome predictions in HIV patients. Swiss HIV Cohort Study.

Transforming natural units of laboratory markers of HIV disease may improve their ability to predict clinical outcomes. The authors examined this issue within a prospective study of 394 patients enrolled in the Swiss HIV Cohort Study (SHCS) between 1991 and 1993. Baseline predictors included CD4+ and CD8+ cell counts, HIV RNA levels, beta2-microglobulin, and age. Outcomes were death and clinical progression. A range of power transformations was applied to each predictor, and the goodness-of-fit of the corresponding proportional hazards models was assessed. The prognostic value of all laboratory variables could be improved on by power transformations. To predict either outcome variable, the "best" transformation of HIV RNA copies and CD8+ cell counts was the logarithm; for beta2-microglobulin, it was power -2. For CD4+ cell counts, the best transformation depended on the outcome variable: it was power 0.2 when predicting survival, and power 0.4 when predicting clinical progression. The single best predictor variable was the ratio of HIV RNA copies per CD4+ cell, for both death (logarithmic transformation) and clinical progression (power -0.1 transformation). Natural units of laboratory variables are not optimal for the prediction of clinical events in HIV-infected patients. Which transformation is best depends on the predictor under consideration.

Adolescent↗
PubMed1998

A critical assessment of the prognostic value of HIV-1 RNA levels and CD4+ cell counts in HIV-infected patients. The Swiss HIV Cohort Study.

OBJECTIVE: To determine to what extent human immunodeficiency type 1 (HIV-1) RNA levels and CD4+ cell counts predict clinical outcomes in a general HIV-1-infected population. METHODS: Community-based prospective study (Swiss HIV Cohort Study) including 394 HIV-1-infected patients, randomly selected from 4 strata of CD4+ cell counts (0 to < 0.05, 0.05 to < 0.20, 0.20 to < 0.50, and > or = 0.50 x 10(9)/L). Levels of HIV-1 RNA, CD4+ cell counts, and other variables were evaluated from samples collected between 1991 and 1993 for their ability to predict death and clinical progression. RESULTS: Patients were followed up on average for 29 months. Baseline HIV-1 RNA levels, CD4+ cell counts, clinical stage, and beta 2-microglobulin levels independently predicted survival, whereas only HIV-1 RNA levels and CD4+ cell counts independently predicted clinical progression. Multivariate relative hazards (RHs) for death ranged from 1.0 to 5.4 across quartiles of CD4+ counts, but only from 1.0 to 1.8 across quartiles of HIV-1 RNA. For clinical progression, gradients of risk were similar for CD4+ counts (1.0-4.2) and for HIV-1 RNA (1.0-3.1). In patients with CD4+ cell counts less than 0.05 x 10(9)L, HIV-1 RNA levels predicted neither death nor clinical progression. Finally, the number of HIV-1 RNA copies per CD4+ cell was the best predictor of death (multivariate RH, 1.0-9.7 across quartiles) and clinical progression (multivariate RH, 1.0-4.1). CONCLUSIONS: Levels of HIV-1 RNA and CD4+ cell counts provided independent and complementary information on clinical outcomes. The RNA/CD4+ ratio was the best single predictor. In patients who had fewer than 0.05 x 10(9)/L CD4+ cells, HIV-1 RNA levels had little prognostic value.

Adult↗
PubMed1998

A randomized double-blind controlled study of 6 months of oral nutritional supplementation with arginine and omega-3 fatty acids in HIV-infected patients. Swiss HIV Cohort Study.

OBJECTIVE: To evaluate the effects of an oral nutritional supplement enriched with two potentially immunostimulant compounds (arginine and omega-3 fatty acids) on the changes in food intake, body composition, immune parameters and viraemia in HIV-infected outpatients. DESIGN: Six-month prospective randomized double-blind controlled study. SETTING: University hospital outpatient nutrition clinic. PATIENTS: Sixty-four HIV-infected outpatients with CD4 lymphocyte count > or = 10O x 10(6)/l. INTERVENTION: All patients received a daily oral nutritional supplement (606 kcal supplemented with vitamins, trace elements and minerals). In addition, half of the patients were randomized to receive 7.4 g arginine plus 1.7 g omega-3 fatty acids. MAIN OUTCOME MEASURES: Disease progression measured by AIDS-defining events, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors, nutritional status determined by anthropometric, bioelectrical impedance and dietetic assessment. RESULTS: Fifty-five patients completed the protocol. Compliance with and tolerance of oral nutritional supplement during the 6-month period was excellent. In both groups of patients the following were found: total energy intake was transiently increased and then returned to baseline level; nitrogen/energy intake ratio was increased throughout the study; gain of body weight and fat mass were approximately 2 and 1kg, respectively, over 6 months, and were similar in both groups. In addition, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors remained statistically unchanged and were similar in both groups. CONCLUSIONS: Enrichment of an oral nutritive supplement with arginine and omega-3 fatty acids did not improve immunological parameters. However, body weight increased in both groups.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Protein encapsulation within polyethylene glycol-coated nanospheres. I. Physicochemical characterization.

The development of injectable nanoparticulate "stealth" carriers for protein delivery is a major challenge. We have shown the possibility of entrapping human serum albumin (HSA) in polyethylene glycol (PEG)-coated monodisperse biodegradable nanospheres with a mean diameter of about 200 nm, prepared from amphiphilic diblock PEG-polylactic acid (PLA) copolymers, with loadings up to 9% (w/w). Microscopic techniques and surface analysis studies enabled us to prove that the protein was well entrapped and not adsorbed onto the particle surface. Zeta potential and water uptake studies corroborated that part of the PEG chains are located in the nanosphere matrix. Water uptake in the nanospheres was related to their chemical composition, i.e., the respective wt% of PEG and PLA in the matrix, and not on their fabrication procedure. The hydrophilic PEG blocks absorbed up to 130% (w/w) water, whereas PLA absorbed only about 10% (w/w). However, the rate of swelling at the beginning of the process was related to the structure of the matrix, more particularly to the manner in which PEG was disposed at the surface. Furthermore, it was shown that the PEG "brush" at the nanosphere surface drastically reduces HSA adsorption on the PEG-PLA nanospheres compared to the PLA ones.

Adsorption↗
PubMed1998

Treatment of chronic hepatitis C with alpha-interferon plus ofloxacin in patients not responding to alpha-interferon alone.

BACKGROUND/AIMS: Ofloxacin, a quinolone antibiotic, was recently shown to increase the primary response rate to alpha-interferon treatment of chronic hepatitis C. METHODS: Fifty-five patients with chronic hepatitis C were scheduled to receive 3 MU of a-interferon, three times a week, for 1 year. After 3 months of therapy, patients who were still HCV RNA-positive in serum started receiving a combined regimen with 3 MU of alpha-interferon, three times a week, plus ofloxacin, 600 mg daily, per os. After 3 months of combined therapy, patients with undetectable serum HCV RNA continued the combined regimen for another 6 months, whereas patients who were still HCV RNA-positive were definitively considered as non-responders and withdrawn from the study. Serum HCV RNA levels were quantitatively evaluated after 3 months of therapy with a-interferon alone and compared with those detected after 3 months of combined regimen. RESULTS: Among the 54 patients who completed the first 3 months of treatment, 32 (59.3%) still had HCV RNA detectable in serum and started receiving the ofloxacin/alpha-interferon therapy. Among the 26 patients who completed the 3 additional months of combined regimen, only one showed a virological response: this patient maintained a complete response to the end of combined treatment, but relapsed thereafter. The combination therapy had no effect on the serum HCV RNA or alanine aminotransferase levels. CONCLUSIONS: The combined administration of alpha-interferon and ofloxacin to patients with chronic hepatitis C who have not responded to alpha-interferon alone does not increase the primary virological response rate.

Adult↗
PubMed1998

Detection of intrahepatic hepatitis C virus replication by strand-specific semi-quantitative RT-PCR: preliminary application to the liver transplantation model.

BACKGROUND/AIMS: Although the hepatitis C virus infection recurs in virtually all patients after liver transplantation, up to 50% of patients may not have histological recurrent hepatitis 1 year after liver transplantation. To study the relationship between hepatitis C virus infection and liver disease after liver transplantation, we compared the intrahepatic hepatitis C virus replication levels with the liver histopathology among liver transplant recipients. METHODS: The intrahepatic negative-strand HCV RNA (i.e. the putative hepatitis C virus replication intermediate RNA) was evaluated by a semi-quantitative, strand-specific reverse transcriptase-polymerase chain reaction in 44 liver specimens from 23 patients with hepatitis C virus reinfection after liver transplantation. Results were compared with the time from liver transplantation, presence, grading and staging of the recurrent hepatitis, amount of hepatitis C virus antigens in the liver and serum HCV RNA levels. RESULTS: Negative-strand HCV RNA was detected in 42 liver specimens as early as 7 days after liver transplantation. Its titers correlated with the amount of intrahepatic hepatitis C virus antigens, but not with HCV RNA levels in serum. Levels of negative-strand HCV RNA in 19 specimens without hepatitis were comparable to those seen in 25 specimens with hepatitis (p=0.492), and were unrelated to the liver disease grading and staging scores. The intrahepatic hepatitis C virus replication could occasionally precede the recurrence of the hepatitis by several months. CONCLUSIONS: Molecular evidence has been obtained for intrahepatic hepatitis C virus replication occurring early after liver transplantation. The level of replication is not correlated with the development of recurrent hepatitis, suggesting that hepatitis C virus may replicate without inducing morphological evidence of liver damage.

Adult↗
PubMed1998

The use of polymerase chain reaction in plasma pools for the concomitant detection of hepatitis C virus and HIV type 1 RNA.

BACKGROUND: Detection of viral nucleic acids might increase blood transfusion safety through the detection of recently infected blood donors during the preseroconversion window period. Individual screening is difficult to apply, because of technical and financial constraints. STUDY DESIGN AND METHODS: A polymerase chain reaction (PCR)-based assay including a polyethylene glycol precipitation step was developed for the concomitant detection of hepatitis C virus (HCV) and HIV type 1 (HIV-1) RNA in plasma pools corresponding to 50 blood donations by the use of commercial assays. RESULTS: The assay had a sensitivity of less than 33 copies per mL for HCV RNA and 1000 copies per mL for HIV-1 RNA for each individual sample included in the pool. The eight preseroconversion samples with HCV RNA between 1,250 and 762,000 copies per mL were all detected when 100-microL aliquots from the samples were introduced into 5-mL pools of 50 blood donations. CONCLUSIONS: A PCR-based pooling assay associating a prepurification step with polyethylene glycol allows for the screening of blood donations for HCV and HIV-1 RNA without marked loss of sensitivity from that seen with commercially available assays. This procedure might increase blood safety through systematic screening of blood donations at relatively low cost.

HIV Infections↗
PubMed1998

Virus burden in lymph nodes and blood of subjects with primary human immunodeficiency virus type 1 infection on bitherapy.

At present, it is not known whether undetectable plasma viremia corresponds to an absence of human immunodeficiency virus type 1 (HIV-1) replication in lymphoid tissues. This issue has been explored in 11 subjects with primary HIV-1 infection treated with zidovudine plus didanosine by evaluating virologic markers in blood and lymphoid tissues 9-18 months after initiation of treatment. These markers include plasma viremia, measured with a sensitive assay with a detection limit of 20 HIV-1 RNA copies/mL, infectious virus titers and proviral DNA in lymph node mononuclear cells, and HIV-1 RNA in lymphoid tissue. Five subjects had plasma viremia <20 copies/mL and showed no evidence of viral replication in lymphoid tissue. Six subjects had both detectable plasma viremia and evidence of HIV-1 RNA in lymphoid tissue. The results indicate that absence of detectable HIV RNA in lymphoid tissue is associated with viremia levels of HIV-1 RNA <20 copies/mL.

Adenoids↗
PubMed1998

Severity and prognosis of acute human immunodeficiency virus type 1 illness: a dose-response relationship.

This study examined the relationship between the severity of acute human immunodeficiency virus type 1 (HIV-1) illness and disease progression and death. The population included 218 patients with acute HIV-1 illness and 41 asymptomatic patients who underwent HIV-1 seroconversion; the patients were followed up prospectively. We analyzed progression to Centers for Disease Control and Prevention clinical categories B and C (AIDS-defining conditions) and death according to an additive clinical score (CS) based on six predictive clinical features at the time of acute HIV-1 infection. Compared with patients with a CS of 0 (asymptomatic patients), those with a CS of 3-4 and 5-6 had faster progression to category B disease (adjusted hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.01-1.92; and HR, 1.80; 95% CI, 1.34-2.40; respectively); those with a CS of 5-6 had faster progression to category C disease (HR, 1.37; 95% CI, 1.01-1.89) and death (HR, 2.05; 95% CI, 1.27-3.32). Thus, the number of symptoms and signs at the time of acute HIV-1 illness affects disease progression and survival, even in symptomatic patients who have undergone seroconversion.

Acute Disease↗
PubMed1998

Detection of human immunodeficiency virus type 1 (HIV-1) RNA in pools of sera negative for antibodies to HIV-1 and HIV-2.

A total of 234 pools were prepared from 10,692 consecutive serum samples negative for antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 collected at five virological laboratories (average pool size, 45 serum samples). Pools were screened for the presence of HIV-1 RNA by a modified commercial assay (Amplicor HIV-1 Monitor test) which included an additional polyethylene glycol (PEG) precipitation step prior to purification of viral RNA (PEG Amplicor assay). The sensitivity of this assay for HIV-1 RNA detection in individual serum samples within pools matches that of standard commercial assays for individual serum samples, i.e., 500 HIV-1 RNA copies per ml. Five pools were identified as positive, and each one contained one antibody-negative, HIV-1 RNA-positive serum sample, corresponding to an average of 1 infected sample per 2,138 serum samples. Retrospective analysis revealed that the five HIV-1 RNA-positive specimens originated from individuals who had symptomatic primary HIV-1 infection at the time of sample collection and who were also positive for p24 antigenemia. We next assessed the possibility of performing the prepurification step by high-speed centrifugation (50,000 x g for 80 min) of 1.5-ml pools containing 25 microl of 60 individual serum samples, of which only 1 contained HIV-1 RNA (centrifugation Amplicor assay). The sensitivity of this assay also matches the sensitivities of standard commercial assays for HIV-1 RNA detection in individual serum samples. The results demonstrate that both assays with pooled sera can be applied to the screening of large numbers of serum samples in a time- and cost-efficient manner.

Centrifugation↗
PubMed1998

Switch to unusual amino acids at codon 215 of the human immunodeficiency virus type 1 reverse transcriptase gene in seroconvertors infected with zidovudine-resistant variants.

Sequences of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) domain were determined by direct sequencing of HIV-1 RNA in successive plasma samples from eight seroconverting patients infected with virus bearing the T215Y/F amino acid substitution associated with zidovudine (ZDV) resistance. At baseline, additional mutations associated with ZDV resistance were detected. Three patients had the M41L amino acid change, which persisted. Two patients had both the D67N and the K70R amino acid substitutions; reversion to the wild type was seen at both positions in one of these patients and at codon 70 in the other one. Reversion to the wild type at codon 215 was observed in only one of eight patients. Unusual amino acids, such as aspartic acid (D) and cysteine (C), appeared at position 215 in four patients during follow-up. These variants isolated by coculturing were sensitive to ZDV. Overgrowth of these variants suggests that they have better fitness than the original T215Y variant. Intraindividual nucleoside substitutions over time were 10 times more frequent in codons associated with ZDV resistance (41, 67, 70, 215, and 219) than in other codons of the RT domain. The predominance of nonsynonymous substitutions observed over time suggests that most changes reflect adaptation of the RT function. The variance in sequence evolution observed among patients, in particular at codon 215, supports a role for chance in the evolution of the RT domain.

Amino Acids↗
PubMed1998

Dynamics of the sub-nuclear distribution of Modulo and the regulation of position-effect variegation by nucleolus in Drosophila.

modulo belongs to the class of Drosophila genes named 'suppressor of position-effect variegation', suggesting the involvement of the encoded protein in chromatin compaction/relaxation processes. Using complementary procedures of cell fractionation, immunolocalisation on mitotic and polytene chromosomes and cross-linking/immunoprecipitation of genomic DNA targets, we have analysed the sub-nuclear distribution of Modulo. While actually associated to condensed chromatin and heterochromatin sites, the protein is also abundantly found at nucleolus. From a comparison of Modulo pattern on chromosomes of different cell types and mutant lines, we propose a model in which the nucleolus balances the Modulo protein available for chromatin compaction and PEV modification. At a molecular level, repetitive elements instead of rDNA constitute Modulo DNA targets, indicating that the protein directly contacts DNA in heterochromatin but not at the nucleolus. Consistent with a role for Modulo in nucleolus activity and protein synthesis capacity, somatic clones homozygous for a null mutation express a cell-autonomous phenotype consisting of growth alteration and short slender bristles, characteristic traits of Minute mutations, which are known to affect ribosome biogenesis. The results provide evidence suggesting that Modulo participates in distinct molecular networks in the nucleolus and heterochromatin and has distinct functions in the two compartments.

Animals↗
PubMed1998

IgM anti-hepatitis C virus core antibodies as marker of recurrent hepatitis C after liver transplantation.

The differential diagnosis of recurrent hepatitis C following orthotopic liver transplantation (OLT) may be difficult. We evaluated the diagnostic significance of IgM anti-hepatitis C virus (anti-HCV) core antibodies in 27 patients undergoing OLT because of HCV-associated cirrhosis. Serial serum samples collected before and after OLT were tested for the presence of IgM anti-HCV core antibodies. Results were compared with the histological evidence of liver damage, the presence, level, and genotype of serum HCV RNA and the degree of immunosuppression. All patients underwent recurrent HCV infection. Recurrent hepatitis was diagnosed histologically in 21 patients an average of 48 weeks after OLT (range 2-209 weeks): 18 had persistence or (re-)appearance of the IgM anti-HCV core after OLT, one lost the IgM anti-HCV core after OLT, and two never secreted IgM anti-HCV core either before or after OLT. The remaining six patients did not develop recurrent hepatitis after a follow-up of 44-241 weeks from OLT; in these patients, IgM anti-HCV core either disappeared (1 case) or decreased (1 case) after OLT or were persistently negative throughout the study (4 cases). Thus, 18/21 patients with recurrent hepatitis, but only one of six without recurrent hepatitis, secreted IgM anti-HCV core after OLT (P < 0.05). The IgM anti-HCV core levels were not correlated with the level or genotype of serum HCV RNA or the degree of immunosuppression. In conclusion, secretion of IgM anti-HCV core antibodies after OLT seems associated with recurrence of HCV-associated liver disease and may have diagnostic significance.

Adult↗
PubMed1997

Glove selection.

Explore the source record for details and available documents.

Decision Making↗
PubMed1997

Detection of low HIV-1 RNA levels in plasma.

HIV-1 viremia is a marker of choice for staging, prognosis, and monitoring treatment efficiency in HIV infection. Among the commercial assays, the Amplicor HIV Monitor (Roche, Basel, Switzerland) test has the highest sensitivity for HIV-1 RNA quantitation in plasma with a detection limit of 200 copies per milliliter. To measure HIV-1 viremia below this threshold, boosted versions of the Amplicor assay were developed by adding a centrifugation step prior to RNA extraction and by decreasing dilution factors. In the boosted version, the increase in analytical sensitivity for HIV-1 RNA detection directly correlates with the input of plasma. For 1,500 microl of plasma, the sensitivity of the assay increases by a factor of 30. For routine clinical analysis, we use a boosted assay format with an input plasma volume of 500 microl and a lower detection limit of 20 copies/milliliter. Coefficients of intra- and interassay variation are similar to those reported for the standard assay (approximately 30%). Thirteen (45%) of 29 plasma samples of HIV-infected individuals with undetectable viremia in the standard assay had detectable viremia between 20 and 200 copies/milliliter.

HIV Infections↗