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Biomedical subjects

E Bernasconi

Publications and source records attributed to E Bernasconi.

At least 37 records · Page 2Linked to original sources
PubMed2000

[HIV superinfection: myth or reality?].

Most viral infections result in lifelong immunity against the virus, which prevents subsequent superinfection. In the light of recent findings on recombination of different viral clades, infection with two different HIV strains is unlikely to occur during primary infection. However, it is unclear whether true superinfection occurs during chronic HIV infection. If it does occur, superinfection could constitute a risk for HIV-concordant couples, since transmission of drug-resistant or more virulent viruses may result in worsening of the disease or treatment failure. We review the available data on superinfection and conclude that HIV-discordant couples should be informed of the theoretical risk of superinfection, especially where only one partner is receiving effective antiretroviral treatment.

AIDS-Related Opportunistic Infections↗
PubMed2000

The role of abacavir (ABC, 1592) in antiretroviral therapy-experienced patients: results from a randomized, double-blind, trial. CNA3002 European Study Team.

OBJECTIVE: To compare the antiviral activity of abacavir (ABC) with stable background therapy (SBG) and SBG alone in antiretroviral therapy-experienced subjects as demonstrated by the proportion of subjects with plasma HIV-1 RNA < or = 400 copies/ml, plasma HIV-1 RNA and CD4 cell count profiles, and safety and tolerance of the two regimens over 16 weeks. DESIGN: One-hundred and eighty-five HIV-1 infected adults, with CD4 cell counts > or = 100 x 10(6)/l and plasma HIV-1 RNA of 400-50,000 copies/ml and who had received SBG therapy for at least 12 weeks, were randomized to receive ABC (300 mg twice daily) or placebo in a double blind, multi-centre study. METHODS: Antiretroviral activity was assessed by measuring changes in plasma HIV-1 RNA levels and CD4 cell counts. Genotypic and phenotypic resistance was determined at baseline and week 16. Evaluation of safety and tolerance was based on clinical adverse events and laboratory analyses. RESULTS: At week 16 significantly more subjects receiving ABC + SBG had plasma HIV-1 RNA < or = 400 copies/ml (36/92, 39%) than subjects receiving SBG alone (7/93, 8%; P < 0.001). A similar response was observed in both the lamivudine naive and lamivudine-experienced subjects. The presence of the M184V mutation did not preclude an antiviral response to ABC; 73% of subjects with the M184V mutation alone experienced a > or = 1.0 log10 copies/ml reduction in plasma HIV-1 RNA or had a value of < or = 400 copies/ml by week 16. CONCLUSIONS: ABC was generally well tolerated and exerted significant antiviral effect when added to combination antiretroviral therapy over 16 weeks.

Adolescent↗
PubMed1999

AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study.

CONTEXT: Acquired immunodeficiency syndrome-related opportunistic illnesses (Ols) continue to occur after initiation of potent antiretroviral therapy in patients with human immunodeficiency virus (HIV) infection. Risk factors for clinical progression to Ols during potent therapy are not well defined. OBJECTIVE: To examine the incidence of and risk factors for Ols among patients treated with potent antiretroviral therapy in a population-based study. DESIGN: The Swiss HIV Cohort Study, a prospective cohort study of adult HIV-infected persons. SETTING: Seven study centers throughout Switzerland. PATIENTS: A total of 2410 cohort study participants with a potential follow-up of at least 15 months after starting potent therapy between September 1995 and December 1997. MAIN OUTCOME MEASURES: Disease-specific incidence of Ols during the 6 months preceding potent antiretroviral therapy and at 3 intervals after initiating therapy; risk factors for development of Ols during therapy. RESULTS: Of the 2410 participants, 143 developed 186 Ols after initiation of potent antiretroviral therapy. Incidence of any OI decreased from 15.1 per 100 person-years in the 6 months before therapy to 7.7 in the first 3 months after starting treatment, 2.6 in the following 6 months, and 2.2 per 100 person-years between 9 and 15 months. Reductions in incidence ranged from 38% per month for Kaposi sarcoma (P<.001) to 5% per month for non-Hodgkin lymphoma (P = .31). Baseline CD4 cell count continued to predict the risk of disease progression after initiating potent therapy. Compared with CD4 cell counts above 200 x 10(6)/L, the hazard ratio for developing Ols was 2.5 (95% confidence interval [CI], 1.4-4.5) for counts between 51 and 200 x 10(6)/L and 5.8 (95% CI, 3.2-10.5) for counts below 51 x 10(6)/L at baseline. Independent of baseline CD4 cell count, a rise in CD4 cell count by 50 x 10(6)/L or more and undetectable HIV-1 RNA in plasma (<400 copies/mL) by 6 months reduced risk of subsequent events, with hazard ratios of 0.32 (95% CI, 0.20-0.52) and 0.39 (0.24-0.65), respectively. CONCLUSIONS: Our data indicate that the risk of developing an OI for a person receiving potent antiretroviral therapy is highest during the initial months of therapy. Baseline CD4 cell count and immunologic and virologic response to treatment were strong predictors of disease progression in patients receiving potent therapy. Individuals with CD4 cell counts of 50 x 10(6)/L or below may need close clinical surveillance after initiation of potent therapy.

AIDS-Related Opportunistic Infections↗
PubMed1999

Why is highly active antiretroviral therapy (HAART) not prescribed or discontinued? Swiss HIV Cohort Study.

In this cross-sectional survey conducted at the end of 1997 among the physicians of participants of the Swiss HIV Cohort Study (SHCS), 1487 of 2154 patients (69.0%) were treated with highly active antiretroviral treatment (HAART) defined as triple therapy with a combination of one or two reverse transcriptase inhibitors, and one or two protease inhibitors; 541 patients (25.1%) had never received such treatment. The physician's perception that the patient would not comply with treatment was one reason for not prescribing HAART to 20% of these patients (110). Physicians indicated that the most common reasons for the patient to refuse HAART were the fear of side effects (18%) and the patient's perception that treatment was too complicated (18%). Among 126 patients (5.8%) no longer receiving HAART, the most common reasons for discontinuing treatment were actual side effects (61%) or the fear of side effects (25%). Overall, 16% of patients did not receive therapy in accord with official Swiss guidelines. Multivariate logistic regression analysis indicated that patients with lower education, active intravenous drug users outside of a drug substitution program, and those who acquired HIV infection through intravenous drug use had a significantly higher risk of inadequate treatment. The physician's judgment of patient adherence and the physician's perception of the patient's fear of side effects are critical for the prescription of HAART. Physicians should address these issues to prevent unilateral withholding of treatment and increase the proportion of patients who may benefit from current antiretroviral therapy.

Anti-HIV Agents↗
PubMed1999

Discontinuation of primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1-infected adults treated with combination antiretroviral therapy. Swiss HIV Cohort Study.

BACKGROUND: It is unclear whether primary prophylaxis against Pneumocystis carinii pneumonia can be discontinued in patients infected with the human immunodeficiency virus (HIV) who are successfully treated with combination antiretroviral therapy. We prospectively studied the safety of stopping prophylaxis among patients in the Swiss HIV Cohort Study. METHODS: Patients were eligible for our study if their CD4 counts had increased to at least 200 cells per cubic millimeter and 14 percent of total lymphocytes while they were receiving combination antiretroviral therapy, with these levels sustained for at least 12 weeks. Prophylaxis was stopped at study entry, and patients were examined every three months thereafter. The development of P. carinii pneumonia was the primary end point, and the development of toxoplasmic encephalitis the secondary end point. RESULTS: Of the 262 patients included in our analysis, 121 (46.2 percent) were positive for IgG antibodies to Toxoplasma gondii at base line. The median CD4 count at study entry was 325 per cubic millimeter (range, 210 to 806); the median nadir CD4 count was 110 per cubic millimeter (range, 0 to 240). During a median follow-up of 11.3 months (range, 3.0 to 18.8), prophylaxis was resumed in nine patients, and two patients died. There were no cases of P. carinii pneumonia or toxoplasmic encephalitis. The one-sided upper 99 percent confidence limit for the incidence of P. carinii pneumonia was 1.9 cases per 100 patient-years (based on 238 patient-years of follow-up). The corresponding figure for toxoplasmic encephalitis was 4.2 per 100 patient-years (based on 110 patient-years of follow-up). CONCLUSIONS: Stopping primary prophylaxis against P. carinii pneumonia appears to be safe in HIV-infected patients who are receiving combination antiretroviral treatment and who have had a sustained increase in their CD4 counts to at least 200 cells per cubic millimeter and to at least 14 percent of total lymphocytes.

AIDS-Related Opportunistic Infections↗
PubMed1999

The NADP-dependent glutamate dehydrogenase gene from Penicillium chrysogenum and the construction of expression vectors for filamentous fungi.

The gdhA gene encoding the NADP-dependent glutamate dehydrogenase activity from Penicillium chrysogenum has been isolated and characterized for its use in gene expression. The nucleotide sequence of a 2816-bp genomic fragment was determined, showing an open reading frame of 1600 bp interrupted by two introns, of 160 bp and 57 bp respectively, with fungal consensus splice-site junctions. The predicted amino acid sequence revealed a high degree of identity to glutamate dehydrogenase enzymes, especially to those from the fungi Aspergillus nidulans (82%) and Neurospora crassa (78%). The gdhA gene was found to be present in a single copy in the genome of several P. chrysogenum strains with different penicillin productivity. The use of the gdhA promoter for homologous and heterologous gene expression in fungi and Escherichia coli was analyzed. Heterologous gene expression was ascertained by the construction of gene fusions with the lacZ gene from E. coli and the bleomycin-resistance determinant (bleR) from Streptoalloteichus hindustanus. Homologous gene expression was shown through the use of the penicillin-biosynthetic genes pchC and penDE from P. chrysogenum and the cephalosporin biosynthetic genes cefEF and cefG from Acremonium chrysogenum.

Amino Acid Sequence↗
PubMed1999

Metabolic effects of protease inhibitor therapy.

Fat redistribution (lipodystrophy) and metabolic anomalies are reported increasingly in HIV-infected patients being treated with protease inhibitors. The incidence of these side effects ranges from 5% to 75% in such patients, who often complain of spontaneous fat wasting in the face, arms, or legs, with or without central obesity. Hyperlipidemia and insulin resistance are almost always associated with lipodystrophy. We review the metabolic complications of antiretroviral therapies and discuss possible therapeutic interventions.

Anti-HIV Agents↗
PubMed1998

A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for HIV infection. The Swiss HIV Cohort Study.

OBJECTIVE: To explore the short-term effects on surrogate markers for HIV progression of didanosine (ddl) plus stavudine (d4T), with or without hydroxyurea. DESIGN: Randomized, double-blinded, prospective study. SETTING: Swiss HIV Cohort Study. PATIENTS: A total of 144 patients (75% antiretroviral-naive) were studied (mean baseline HIV-1 RNA, 4.53 log10 copies/ml; mean CD4 cell count, 370 x 10(6)/l). INTERVENTION: Patients received ddl (200 mg twice daily) plus d4T (40 mg twice daily), with additional hydroxyurea (500 mg twice daily) or placebo. MAIN OUTCOME MEASURES: The primary endpoint was a reduction of viraemia below 200 copies/ml after 12 weeks. At that time, patients who did not reach the primary endpoint were withdrawn in the hydroxyurea arm, whereas patients in the placebo group had the option of adding hydroxyurea to ddl and d4T. All patients were followed until week 24. RESULTS: After 12 weeks, 54% of the patients randomized to hydroxyurea had viraemia below 200 copies/ml, compared with 28% on placebo (P < 0.001). Using an ultrasensitive assay with a limit of detection of 20 copies/ml, 19% of patients receiving hydroxyurea had viraemia levels below 20 copies/ml, compared with 8% on placebo (P = 0.05). Mean decrease in HIV-1 RNA was 2.3 and 1.7 log10 copies/ml for hydroxyurea and placebo groups, respectively (P = 0.001). Hydroxyurea was found to induce lymphopenia (-124 x 10(6)/l). Increase in CD4 cell counts was +28 x 10(6)/l during hydroxyurea treatment compared with +107 x 10(6)/l on placebo (P = 0.001). CONCLUSIONS: Hydroxyurea improved the antiviral activity of d4T and ddl over a 12-week period, but was associated with a smaller increase in CD4 cell counts due to hydroxyurea-induced lymphopenia.

Adult↗
PubMed1998

Didanosine plus stavudine with or without hydroxyurea in HIV-1-infected patients: 1 year follow-up. Swiss HIV Cohort Study.

A total of 144 human immunodeficiency virus (HIV)-infected patients (mean CD4 cell count, 367 cells/mm3) were included in a double-blind placebo-controlled trial testing the efficacy on surrogate markers of HIV progression of the combination didanosine (2',3'-dideoxyinosine or DDI) plus stavudine (2',3'-didehydro-2',3'-dideoxythymidine or D4T) with or without hydroxyurea. The primary end point was a reduction of HIV RNA levels to below 200 copies/ml after 12 weeks of treatment. The results showed that the triple combination was associated with a more profound decrease in HIV RNA with an increased proportion of patients with viraemia < 200 copies/ml. This effect persisted for the majority of the patients after a 48 week follow-up. In contrast, the increase in CD4 cell counts was less in patients treated with hydroxyurea because of lymphopenia, and adverse events were more frequent in hydroxyurea-treated patients. In conclusion, the addition of hydroxyurea consistently improved the antiviral activity of the didanosine/stavudine combination over a 48 week follow-up. Increased toxicity and decreased effect on CD4 cell counts might inspire caution.

Anti-HIV Agents↗
PubMed1997

Amphetamine-induced disruption of latent inhibition is not reinforcer-mediated.

Latent inhibition (LI) refers to retarded conditioning to a stimulus that had been repeatedly preexposed without consequences, as compared with a nonpreexposed stimulus. Amphetamine disrupts LI, and this effect was suggested to result from enhanced switching to respond according to the stimulus-reinforcer contingency. Recently, it has been argued that amphetamine disrupts LI by increasing the impact of the reinforcer. This implies that amphetamine should produce stronger conditioning in the nonpreexposed group and that its influence on LI can be modified only by changing reinforcer parameters. We report two studies, using an off-baseline conditioned emotional response procedure in rats licking for water, that question both predictions. In the first study, a meta-analysis based on 23 replications of the effect of amphetamine on LI, using tone as the preexposed stimulus, showed that LI is significantly attenuated due to drug-induced increased suppression in the preexposed groups only. The second study included two experiments, each using two shock intensities but different preexposed stimuli. Amphetamine disrupted LI at both shock intensities when the stimulus was a steady light, but this effect disappeared when the stimulus was three flashing lights. Thus, the effect of amphetamine could not be modified by manipulating shock intensity, but was modifiable by manipulating the nature of the preexposed stimulus. The results are inconsistent with the hypothesis that amphetamine-induced disruption of LI is solely mediated by drug-induced changes in the effects of reinforcers.

Animals↗
PubMed1997

Amphetamine-induced disruption of latent inhibition depends on the nature of the stimulus.

It is well documented that latent inhibition (LI), i.e. slower conditioning to a stimulus that had been repeatedly pre-exposed without consequences, compared to a non-pre-exposed stimulus, is prevented by amphetamine. Recently, we found that the effects of amphetamine on LI, as assessed in an off-baseline conditioned emotional response (CER) procedure, depend on the nature of the pre-exposed stimulus, irrespective of reinforcer intensity. Because these results contrast with a recent finding that a reduction in reinforcer intensity reversed amphetamine-induced attenuation of LI in an on-baseline CER procedure, the present study investigated the effects of amphetamine on LI as a function of the nature of the pre-exposed stimuli and shock intensity, using an on-baseline CER procedure. The effects of amphetamine on post-shock suppression of drinking as well as on activity, were monitored throughout the stages of the CER procedure. Experiment 1 used a 5 s steady light as the pre-exposed and conditioned stimulus, and two shock intensities in conditioning, and Experiment 2 used a 10 s flashing light and two shock intensities. Amphetamine disrupted LI with a steady light at both low and high shock intensities, but failed to disrupt LI with a flashing light at both shock intensities. In addition, the drug disrupted LI in Experiment 3, which increased the duration of the steady light to 10 s and used only low shock intensity, but failed to affect LI in Experiment 4 which used the flashing light on the background of darkness or of light, and only high shock intensity. The effects of amphetamine on LI were not related to its effects on behavioural suppression after footshock, or on activity.

Amphetamine↗
PubMed1996

[Attitude of Swiss Army recruits from Tessin to pain and euthanasia (1992 and 1995)].

Nineteen-year-old Swiss Army conscripts were questioned in 1992 (n = 1361) and 1995 (n = 1050) about their opinions regarding pain and euthanasia. In 1995, 85% (1992: 71%) considered pain as a fundamental part of life, 73% (1992: 77%) thought that the patient himself should decide how to control pain, and 50% (1992: 51%) would accept the idea of euthanasia at the request of a family member with an incurable disease and in pain. Significant differences were found only in correlation to the degree of religious belief.

Adult↗
PubMed1996

Cell surface expression of a functional rubella virus E1 glycoprotein by addition of a GPI anchor.

Rubella virus (RV) envelope glycoproteins E1 and E2 are targeted to the Golgi as heterodimers. While E2 contains a transmembrane Golgi retention signal, E1 is arrested in a pre-Golgi compartment in the absence of E2, and appears to require heterodimerization in order to reach the Golgi. Various forms of E1 with deletions in the ectodomain or lacking the cytoplasmic (CT) and transmembrane (TM) domains, as well as the 29 C-terminal amino acid residues of the ectodomain were also retained intracellularly. We therefore investigated the possibility of targetting E1 to the plasma membrane by addition of a glycosylphosphatidylinositol (GPI) anchor. We found that E1GPI was transported to the cell surface where it retained the hemadsorption activity characteristic of the wild-type E1/E2 heterodimer. Furthermore, coexpression of a mammalian GPI-specific phospholipase D (GPI-PLD) resulted in the release of E1GPI and in constitutive expression of a soluble form of E1. This study thus demonstrates that the GPI anchor has a dominant effect over the E1 pre-Golgi retention signal and that E1 is sufficient for hemadsorption.

Amino Acid Sequence↗
PubMed1994

[Actinobacillus actinomycetemcomitans isolated from a mycetoma (of the forearm)].

Mycetomas are subacute or chronic infections usually localized on unprotected skin areas and caused by fungi or Actinomyces. We report the case of a patient who suffered a splinter injury on his wrist after a motor accident. Six months later a cutaneous abscess with Actinobacillus actinomycetemcomitans developed on his wrist. Complete healing was obtained within 1 month after administration of ceftriaxon and doxycycline. The therapeutic management will be discussed.

Abscess↗
PubMed1994

[Bilateral acute retinal artery necrosis--healing of the second affected eye].

BACKGROUND: The acute retinal necrosis syndrome (ARN) is caused by the Varicella zoster virus or the Herpes simplex virus. However the dosage and duration of the antiviral therapy for prevention of an infection in the second eye or treatment of an infection on an affected fellow eye is still not known. We discuss the timing of a possible steroid treatment and demonstrate in a case report how an acute retinal necrosis syndrome in a fellow eye was successfully treated. PATIENT: First eye: A 27-year-old not immunocompromised patient (HIV-negative) showed 2 months after a febrile state an acute iritis in the right eye. 14 days later an acute retinal necrosis syndrome was observed. The patient received Acyclovir 3 x 750 mg i.v. for 6 days, and afterwards 5 x 200 mg orally for 5 days. The patient developed an inoperable retinal detachment despite therapy. Second eye: Eight days later the fellow eye developed a localized retinal necrosis. Varicella zoster DNA was found in the aqueous humor using the polymerase chain reaction (PCR). The antiviral therapy with Acyclovir was increased from 1.1 g q 12 h (2 x 15 mg/kg/d) to 1.0 g q 8 h (3 x 12.5 mg/kg/d). After 4 weeks the i.v. therapy was followed by an oral therapy of 5 x 800 mg for 12 weeks. This dosage was reduced to 5 x 400 mg for another 12 weeks. The oral therapy with corticosteroids started on the 11th day with 100 mg Prednisone, in slowly reducing dosage during 18 weeks. The fellow eye recovered fully with a visual acuity of 20/20 after 6 months. CONCLUSION: The disease started in the fellow eye with an acute iritis and a secondary glaucoma. These symptoms can be a characteristic prodroma of an acute retinal necrosis syndrome caused by a varicella zoster- or Herpes simplex virus infection, which was not recognized first. Whether a long-term therapy (as described above) is necessary or not is unclear on the basis of a single case report, but we currently recommend the high-dose treatment regimen until further data emerge.

Acyclovir↗