Co-transmission of hepatitis C and G viruses.
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Biomedical subjects
Publications and source records attributed to S Rousseau.
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Vascular endothelial growth factor (VEGF) is a potent chemotactic agent for endothelial cells. Yet the signalling pathways that modulate the motogenic effects of VEGF in vascular endothelial cells are still ill defined. In the present study, we found in primary cultures of human umbilical vein endothelial cells (HUVEC) that VEGF increased cell migration and induced a marked reorganization of the microfilament network that was characterized by the formation of stress fibers and the recruitment of vinculin to focal adhesions. VEGF also stimulated the mitogen activated protein (MAP) kinases ERK (extracellular signal-regulated kinase) and p38 (stress activated protein kinase-2), but not SAPK1/JNK (stress activated protein kinase-1/c-Jun NH2-terminal kinase). Activation of p38 resulted in activation of MAP kinase activated protein kinase-2/3 and phosphorylation of the F-actin polymerization modulator, heat shock protein 27 (HSP27). Inhibiting the VEGF-induced activation of ERK with PD098059 did not influence actin organization or cell migration but totally inhibited the VEGF-induced incorporation of thymidine into DNA. Inhibition of p38 activity by the specific inhibitor SB203580 led to an inhibition of HSP27 phosphorylation, actin reorganization and cell migration. The results indicate that the p38 pathway conveys the VEGF signal to microfilaments inducing rearrangements of the actin cytoskeleton that regulate cell migration. By modulating cell migration, p38 may thus be an important regulator of angiogenesis.
This study estimated the prevalence of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) serological markers among inmates and evaluated inmates' compliance with an HBV immunization programme. During the mandatory consultation at the sexually transmitted disease (STD) clinic of the Marseille Prison (HIV counselling, and syphilis/HIV screening), physicians offered serological testing (anti-HBs, anti-HBc, HbsAg, anti-HIV) and Engerix B vaccination to each entrant. The number participating in the survey is 391/411 (89%); 75% were aged 18 to 35 years and 79% were men; 42% reported having had multiple sexual partners during the last 12 months. Report of an intravenous drug user (IDU) sexual partner was more frequent among women than men (22% vs 8%). Injecting drug use over lifetime was reported by 23%; 27% declared having shared their injection equipment during the last 12 months. 124/267 (32%) had an HBV marker: anti-HBs + only (immunized): 2.3%; anti-HBs + and anti-HBc +: 21.7%; anti-HBc + only: 6.4%; HBsAg +: 1.3%. The HIV seroprevalence was 6% (21% among IDUs). This survey underlines the high HBV and HIV seroprevalence among prisoners and the high proportion of inmates at risk for these infections. There is an urgent need for immunization and education programmes in this population. It demonstrates an HBV immunization programme is feasible and accepted by inmates and staff members.
This study comprised 100 persons with antibodies to hepatitis C virus (HCV), including 77 intravenous drug users (IVDUs). They were tested with serological HCV typing assays (Murex HCV serotyping 1-6 assay; Chiron RIBA HCV Serotyping SIA). Patients with a positive polymerase chain reaction (PCR) for HCV (n = 66) were tested with genotyping molecular assays (Inno-Lipa HCV II test; Sorin GEN-ETI-K HCV typing assay). Comparison of the results of these tests showed that (a) 92% of samples could be typed by one test at least; 44% could be typed by all four tests; 88% could be typed by one serological test at least and 66% by one molecular test at least; (b) 81% of the samples successfully tested with both serological tests gave comparable results; 95% of the samples successfully tested with both molecular tests gave comparable results; (c) when serological and molecular tests yielded different results, sequences in the 5'-non-coding (5' NC) or E1 regions always confirmed the results of the molecular tests; (d) in case of discrepancy between the results of the molecular tests the E1 region sequences confirmed the Sorin test results. It is concluded that the molecular tests compared gave similar results. The fact that the Murex serological test gave comparable results in more than 80% of cases indicates that it is an alternative to the molecular tests for routine diagnosis. However, comparison of the results of this test with those obtained in patients consulting a hepatology department showed that it gave the best results in a population of patients not exposed repeatedly to HCV.
BACKGROUND/AIMS: In several studies markers of hepatitis C virus infection have been shown to be present in alcoholic patients with cirrhosis. Our work was designed to test the likely hypothesis that this association is due to an interaction between hepatitis C virus and alcohol in the pathogenesis of cirrhosis. METHODS: We compared alcohol consumption and repartition of anti-HCV antibodies detected by an immunoblot recombinant assay in 101 male patients with cirrhosis and in 120 male controls. Interactions between anti-hepatitis C virus, alcohol and cirrhosis were calculated using log linear hierarchical models for frequency data. The basis of the method is that an interaction between hepatitis C virus and alcohol implies that a model built on the hypothesis of a role of hepatitis C virus and alcohol in the disease should be improved by a coefficient associated with multiplicative effects of hepatitis C virus and alcohol. RESULTS: In patients with cirrhosis the mean alcohol consumption (148 +/- 100 g per day) and the incidence of positivity for anti-HCV antibodies (45%) were significantly higher than in controls. The results were consistent with a theoretical model built with the hypothesis of an independent role of both alcohol and hepatitis C virus. The goodness of fit between this model and the actual distribution of alcohol consumption and hepatitis C virus markers was not improved by introduction of an interaction between hepatitis C virus and alcohol. CONCLUSIONS: In alcoholic subjects with hepatitis C virus infection, the probability to have cirrhosis seemed to be explained by additive effects of alcohol and hepatitis C virus. From a purely statistical point of view, no interaction between hepatitis C virus and alcohol consumption on a multiplicative scale could be demonstrated.
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BACKGROUND: Injury to the spinal cord is still observed in the neonate. Its prognosis is poor. CASE REPORTS: The first neonate was delivered by cesarean section for breech presentation with hyperextension of the neck. She rapidly developed acute respiratory distress and paraplegia. MRI showed spinal cord hemorrhage involving the cervical and upper thoracic cord with rupture of the cord. The patient died a few weeks later. The second neonate was delivered vaginally in breech presentation without any difficulty. She progressively developed tetraplegia evolving into spasticity. MRI showed stretching of cervical spinal cord. The patient later developed sphincter disturbances, repeated urinary and pulmonary infection and severe scoliosis. CONCLUSIONS: Early prenatal damage to the spinal cord was possible in the first patient. Ultrasonography could help to evaluate the extent of damage. The condition leads to difficult ethical and therapeutic problems.
In order to evaluate the evolution of transfusional hepatitis C in haemophiliacs, we performed a retrospective study of ALT levels and HCV viraemia with a RNA PCR assay in 57 patients. We found that the vast majority of HCV-infected patients remained viraemic (43/57 = 75%) and higher ALT levels correlated with HCV viraemia. Although indicators of the transfusional viral load (age, severity of haemophilia) and HBV co-infection did not correlate with HCV RNA replication, HIV seropositivity was strongly associated with persistence of HCV viraemia (23/25 = 92% in HIV-positive versus 20/32 = 62% in HIV-negative patients), without any correlation with CD4 counts. Genotyping of HCV in the 43 viraemic patients shows more frequent genotype 1 in the HIV-seropositive group (14/23) than in the seronegative group (6/20). Our data emphasize that besides the role of the immunodeficiency status, the genotypes of HCV might be involved in the differences observed in terms of HCV RNA replication between the HIV-seropositive and seronegative haemophiliacs.
Immunoassays have been recently developed that measure the avidity of IgG antibodies to complex microbial antigens and are suitable for serologic diagnosis of infectious diseases. In these avidity ELISAs, protein-denaturing agents are applied either as diluents of patient sera to prevent the immune complexing of IgG (diluting principle), or the preformed complexes are treated with the protein denaturants (eluting principle). We compared four protein denaturants previously used in such assays, in a diagnostic avidity ELISA for rubella IgG. Diethylamine, guanidine, thiocyanate, or urea were applied, by either principle at various concentrations, and thiocyanate, or urea were applied, by either principle at various concentrations, and thiocyanate at an optimum pH. Patient sera obtained recently after primary infection were distinguished from sera representing past rubella immunity by any protein denaturant tested by the eluting principle, which was superior to the diluting principle.
We have previously described a passive inflation method during constant inspiratory flow for measuring total respiratory elastance and resistance during mechanical ventilation in newborns. The simple method for measuring respiratory mechanics had been assessed during decelerating inspiratory flow obtained with pressure controlled ventilation (PCV). We report an application of this method to preterm and full-term mechanically ventilated newborn infants and a comparison with the occlusion method. Twenty-one newborn infants (birth weight 1,060 to 3,650 g; gestational age 26 to 41 weeks), between 1 to 55 days of postnatal age, were enrolled in the study. They were ventilated with a "Servo ventilator 900C," first set in the pressure-controlled mode and then in the volume-controlled mode without changing the tidal volume (VT), inspiratory time or ventilator rate. Flow was measured through a pneumotachograph inserted between the endotracheal tube (ETT) and the breathing circuit; VT was obtained by integration of flow and airway pressure measured directly at the airway opening. Flow, volume, and pressure were plotted on analog X/Y tables to obtain pressure-volume (P/V) and flow-volume (V/V) loops, as well as pressure-time curves. Occlusion was performed by using the end-inspiratory and the end-expiratory pause buttons of the ventilator. The passive inflation method during PCV was based on the analysis of P/V and V/V loops and provided compliance (Crs(PC)infl.), resistance Rrs(PC)infl.) of the respiratory system, and intrinsic positive end-expiratory pressure (PEEP(PC)i,infl.). These values were compared with (1) compliance (Crs(PC)occl.) and intrinsic positive end-expiratory pressure (PEEP(PC)i,occl.) measured by the occlusion method during PCV; (2) static (Crs(VC),occl.) and dynamic (Crs(VC),dyn.) compliance, airway (R(aw)(VC),), tissue (Rrs(VC),visc.) and total resistance (Rrs(VC),occl.), and intrinsic positive end-expiratory pressure (PEEP(VC)i,occl.) measured by the occlusion method during volume-controlled ventilation. Crs(PC),infl. correlated well with Crs(PC),occl., Crs(VC),occl., and Crs(VC),dyn.. Furthermore, Crs(PC),infl. and Crs(VC),dyn. did not differ significantly. Rrs(PC),infl. correlated well and did not differ significantly from total inspiratory resistance, i.e., the sum of R(aw)(VC) and Rrs(VC),vis. PEEPPC,i,infl. correlated well and did not differ significantly from PEEP(PC)i.occl. and from PEEP(VC),i,occl. The passive inflation method can be used during PCV with a decelerating flow waveform. It provides dynamic compliance, inspiratory resistance of the respiratory system, and intrinsic PEEP from the analysis of V/V and P/V loops recorded at the airway opening. This technique is simple to use and well tolerated by preterm and full-term ventilated newborn infants. It can be a good alternative to occlusion methods.
OBJECTIVE: To examine physicians' perceptions, motivations, and influences on their willingness to care for patients with human immunodeficiency virus (HIV). DESIGN: Interviews with 30 physicians. Qualitative content and narrative analyses were performed. SETTINGS: Community-based primary care practices in six moderate-sized cities in the northeastern United States with at least a moderate incidence or prevalence of reported acquired immunodeficiency syndrome cases. PARTICIPANTS: Thirty community-based primary care physicians who had cared for at least two patients with HIV during the previous 2 years. MAIN OUTCOME MEASURE: Qualitative study designed to provide rich descriptive data. RESULTS: Care of patients with HIV was regarded as part of the scope of primary care, and was perceived to be similar to the care of patients with other chronic illnesses. Many physicians were motivated by personal rewards in taking care of patients, intellectual challenge, and desire to serve the underserved. Most believed that practicing physicians have an ethical obligation to care for all patients, regardless of diagnosis. No one "type" of physician could be identified who provides care to patients with HIV. CONCLUSIONS: Primary care physicians can apply their skills in the management of other chronic diseases to the care of patients with HIV. Practicing physicians can find caring for patients with HIV rewarding, stimulating, and enjoyable. Educational programs for physicians need to emphasize psychosocial aspects of HIV care. In addition, physicians need opportunities to recognize and deal effectively with their own emotional responses to the care of patients with HIV.
A baby with acute fetal distress and severe heart malformation presented with persisting hypotonia and muscle weakness. Clinical, electromyography, and muscle biopsy findings were compatible with anterior horn cell disease. Postmortem study showed widespread ischemic necrosis in the anterior gray matter of the spinal cord. This is the first report of anterior spinal artery syndrome in a neonate.
Somatosensory evoked potentials (SEPs) were performed between 31 and 49 weeks postmenstrual age on 33 neonates with extensive cystic leukomalacia. 27 had periventricular leukomalacia (PVL), while six had deep white matter lesions. All but two of the 27 infants with PVL had a reproducible potential at discharge, being delayed in 11 and within the normal range in 14. No potentials could be obtained in any of the infants with cysts in the deep white matter. All surviving infants developed severe neurological sequelae, irrespective of the N1 being delayed or within normal range. These data suggest that in infants with an ultrasound diagnosis of cystic leukomalacia, little additional information with regard to neurodevelopmental outcome is provided by performing median nerve SEPs, especially for those infants in whom the cystic lesions are restricted to the occipital periventricular white matter.
Histone H5, an early marker of the avian erythroid lineage, is expressed at low levels in early erythroid precursors and at higher levels in more mature cells. We show that the increase in H5 expression is due to transcriptional activation of the H5 gene following differentiation of precursor CFU(E). We have found and characterized two upstream enhancers, E1 (between -2233 and -1878 from the site of transcription initiation, +1) and E3 (between -1321 and -1163), and confirmed the presence of a downstream enhancer (C. D. Trainor, S. J. Stamler, and J. D. Engel, Nature [London] 328:827-830, 1987) E7 (between +846 and +1181) which are responsible for the increase in H5 gene transcription. The enhancers had a weak effect in nondifferentiated CFU(E) but a strong effect when the cells were induced to differentiate. Cooperation among the three enhancers, however, was not required for H5 gene activity in the differentiated cells. The enhancers contain binding sites for several ubiquitous and erythroid cell-specific nuclear proteins, including GATA-1, as demonstrated with GATA-1-specific antibodies. Although the GATA sites were required for enhancer function, the concentration of GATA-1, GATA-2, and GATA-3 decreased during cell differentiation, and overexpression of these factors had little effect on H5 transcription. Hence, the differentiation-specific effect of the enhancers is not mediated by changes in relative levels of the GATA factors. Functional analysis of the H5 promoter indicated that the requirement of several elements, including a GC box necessary for transcription enhancement, did not change during the early stages of CFU(E) differentiation. However, the UPE, a positive element in proliferating CFU(E) recognized by the transcription factor H4TF2, was dispensable in the differentiated cells. These results suggest that as the cells enter the final stages of differentiation, there is a reprogramming of the regulatory factors that control H5 transcription and that the enhancers rescue and increase the activity of the promoter.
The authors report two cases of cutaneous recurrent herpes occurring after a neonatal herpes simplex virus type 2 (HSV2) infection and comment on the role of acute or suppressive therapy by aciclovir (ACV). The two infants were not treated by ACV after the neonatal period. None of the recurrent cutaneous herpes episodes was followed by viral widespread. One case reported by Bergström et al on a relapse of HSV2 encephalitis occurring after a cutaneous herpes in a child argues for the use of ACV in recurrent herpes. However, ACV might alter host defense response to HSV2 infection in neonates and children. Thus, it seems not yet recommended to use ACV either as acute or suppressive therapy in recurrent cutaneous herpes unless a progression of the viral disease is noted.
BACKGROUND: Fear of contagion has been identified as a potential deterrent for primary care physicians who would otherwise care for HIV patients. This study examines physicians' fears of occupational HIV transmission and the ways that they cope with those fears. METHODS: Thirty community-based primary care physicians who were caring for HIV patients were interviewed about their experiences with HIV patients and the meanings they ascribe to those experiences. Qualitative content and narrative analysis were used. RESULTS: Fear of contagion was common despite the relatively low reported self-assessment of risk by primary care physicians. Most physicians considered their level of risk acceptable, but for some it seemed to take a high emotional toll. Some physicians identified their fear as "irrational." Physicians reported tension between fear of contagion and ethical responsibility to care for HIV patients. Some physicians were overattentive to infection control measures, whereas others used universal precautions inconsistently. Physicians continued to care for HIV patients despite their fears. Some physicians' family members needed information and reassurance about transmission of HIV. CONCLUSIONS: Some physicians who care for HIV patients are poorly equipped to deal with their own fears. There is a need to examine in greater depth the relationship between fear of contagion and willingness to provide care, and to examine other factors that may be contributing to the expression of these fears.
Expression of histone H5, like that of other erythrocyte specific proteins, declines during the latter stages of erythroid maturation because of a decrease in the rate of gene transcription. Here, we report the isolation of cIBR (chicken initiation binding repressor), a 75 kDa DNA binding glycoprotein from mature chicken erythrocytes that recognizes sequences spanning the transcription start sites of the H5 gene. cIBR was found to repress transcription from the H5 promoter in vitro and this effect could be relieved by mutations that lowered the affinity of the factor for its cognate sequence. cIBR inhibited transcription by interfering with assembly of the initiation complex, but it did not affect transcription from pre-assembled complexes. Consistent with this, binding of bacterially expressed human TFIID to the TATA element prevented subsequent binding of cIBR, although the opposite was not true. This, and the fact that cIBR had no effect when bound in a location upstream from the promoter, suggests that binding of cIBR to the start site region causes repression by direct interference with general transcription factors other than TFIID, possibly TFIIB. cIBR was found in mature and relatively late erythrocytes but not in early erythroid cells which actively transcribe the H5 gene; the transcriptionally active cells contain instead cIBF (chicken initiation binding factor). Purified cIBF is a non-glycosylated 68-70 kDa DNA binding protein(s) which also recognizes the region of transcription initiation of the H5 gene.
A passive inflation method was described for measuring total respiratory elastance and resistance during mechanical ventilation in adult patients (Rossi et al., J Appl Physiol 58:1849, 1985). We applied this method to preterm and full-term mechanically ventilated newborn infants and we compared the results with those obtained by the occlusion method. We performed 37 tests in 16 newborn infants (B.W. 880-4,500 g; G.A. 28-42 weeks), between 1 and 45 days of postnatal age, ventilated with a Servo Ventilator 900C, set in controlled-volume mode. Flow was measured through a pneumotachograph inserted between the endotracheal tube (ETT) and the breathing circuit, tidal volume by integration of flow and airway pressure directly at the airway opening. Flow, volume, and pressure were recorded on an X/Y plotter to obtain pressure-volume (P/V), flow-volume (V/V) loops, and pressure-time curves. Occlusion was performed by using the end-inspiratory and the end-expiratory pause buttons of the ventilator. Analysis of P/V and V/V loops provided respiratory system compliance (Crs, infl.), resistance (Rrs, infl.), and "intrinsic positive end-expiratory pressure" (PEEPi, infl.). These values were compared with Crs, occl., Rrs, occl., and PEEPi, occl. measured by the occlusion method. The measurements were well correlated (Crs, infl./Crs, occl.: r = 0.90; Rrs, infl./Rrs, occl.: r = 0.91; PEEPi, infl./PEEPi, occl.: r = 0.91). Rrs, infl./Rrs, occl. and PEEPi, infl./PEEPi, occl. did not differ significantly. However, Crs, occl. was 15% higher than Crs, infl. (P less than 0.01). The passive inflation method is simple to use and well tolerated in preterm and full-term ventilated newborn infants, it provides accurate results, and can be a good alternative to occlusion methods. It requires, however, a constant inflation flow and adaptation to the ventilator.