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Biomedical subjects

M Battegay

Publications and source records attributed to M Battegay.

At least 127 records · Page 7Linked to original sources
PubMed1994

Elimination of hepatitis delta virus infection after loss of hepatitis B surface antigen in patients with chronic delta hepatitis.

The aim of this study was to evaluate whether patients with chronic hepatitis delta virus (HDV) infection treated with alpha interferon and subsequent loss of hepatitis B surface antigen (HBsAg) eliminate HDV. HDV RNA was detected in 26 of 28 patients with chronic delta hepatitis using the polymerase chain reaction. Seventeen patients in whom HDV RNA was detected were treated with alpha interferon; in 65%, HDV RNA remained detectable during treatment or reappeared after stopping therapy whereas in three patients HDV RNA remained absent (17.5%). HDV RNA became and remained undetectable in serum and liver of two of these three patients who lost HBsAg from serum and in one patient who was intermittently HBsAg negative during therapy. After loss of HBsAg, hepatitis B virus (HBV) DNA was still detectable in the liver, but not HBV RNA, indicating absent or very low HBV replication. Three patients were lost to follow up (17.5%). Two nontreated patients with chronic HDV infection also lost HBsAg during follow up; HDV RNA also became undetectable in their serum. Thus, HDV replication does not persist after the loss of HBsAg. Clearance of HBsAg may be a useful guide to when therapy can be stopped.

Adolescent↗
PubMed1994

Hepatitis delta virus RNA in serum of patients with chronic delta hepatitis.

We studied 28 patients with chronic delta hepatitis for the presence of hepatitis delta virus (HDV) RNA in serum. The hot start polymerase chain reaction (PCR) method, in which the reaction begins at 60-80 degrees C, showed a higher sensitivity than conventional PCR reaction. Additionally, the presence of hepatitis B (HBV) and C virus (HCV) infections were determined by PCR. HDV RNA was detected in 26 patients (93%), HBV DNA in 22 (79%), and HCV RNA in only one. Detection of HDV RNA correlated very well with detection of hepatitis delta antigen by immunostaining in the liver. In six patients HDV RNA was detectable despite the absence of HBV DNA in serum, suggesting that high levels of HBV are not required for HDV replication. Of 29 control patients with chronic hepatitis B without antibody to HDV, none had detectable HDV RNA, while all had HBV DNA in serum. Detection of HDV RNA with PCR proved highly sensitive and specific, demonstrating that virtually all patients with chronic HDV infection had ongoing viral replication.

Adult↗
PubMed1994

Resistance of lymphocytic choriomeningitis virus to alpha/beta interferon and to gamma interferon.

The susceptibility to alpha/beta interferon (IFN-alpha/beta) or to gamma interferon (IFN-gamma) of various lymphocytic choriomeningitis virus (LCMV) strains was evaluated in C57BL/6 mice and in various cell lines. Anti-IFN-gamma treatment in vivo revealed that the LCMV strains Armstrong, Aggressive, and WE were most susceptible to IFN-gamma whereas Traub, Cl 13-Armstrong, and Docile were resistant. The same pattern of susceptibility to recombinant IFN-gamma was observed in vitro. In vivo treatment with anti-IFN-alpha/beta showed a sizeable increase in replication of Aggressive, Armstrong, and WE; effects were less pronounced for Docile, Cl 13-Armstrong, or Traub. Correspondingly, WE, Armstrong, and Aggressive were all relatively sensitive to purified IFN-alpha/beta in vitro, and Cl 13-Armstrong, Docile, and Traub were more resistant. Overall, there was a good correlation between the capacity of LCMV strains to establish a persistent infection in adult immunocompetent mice and their relative resistance to IFN-gamma and IFN-alpha/beta.

Animals↗
PubMed1994

Enhanced establishment of a virus carrier state in adult CD4+ T-cell-deficient mice.

CD4+ T cells play an important role in regulating the immune response; their contribution to virus clearance is variable. Mice that lack CD4+ T cells (CD4-/- mice) and are therefore unable to produce neutralizing antibodies cleared viscero-lymphotropic lymphocytic choriomeningitis virus (LCMV) strain WE when infected intravenously with a low dose (2 x 10(2) PFU) because of an effective CD8+ cytotoxic T-cell (CTL) response. In contrast, infection with a high dose (2 x 10(6) PFU) of LCMV strain WE led to expansion of antiviral CTL, which disappeared in CD4-/- mice; in contrast, CD4+ T-cell-competent mice developed antiviral memory CTL. This exhaustion of specific CTL caused viral persistence in CD4-/- mice, whereas CD4+ T-cell-competent mice eliminated the virus. After infection of CD4-/- mice with the faster-replicating LCMV strain DOCILE, abrogation of CTL response and establishment of viral persistence developed after infection with a low dose (5 x 10(2) PFU), i.e., an about 100-fold lower dose than in CD(4+)-competent control mice. These results show that absence of T help enhances establishment of an LCMV carrier state in selected situations.

Animals↗
PubMed1994

Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia.

The radiographic presentation of Pneumocystis carinii pneumonia (PCP) was studied in 93 consecutive patients to determine the frequency of normal findings on chest roentgenograms and possible correlations with clinical or laboratory findings. The roentgenograms were reviewed by two radiologists in an independent, blinded way and judged with a score distinguishing between none, interstitial, and acinar infiltrates. Discordance mainly between absent versus interstitial and interstitial versus acinar infiltrates occurred in 23% of roentgenograms and was settled by consensus. The majority of patients presented with moderate-to-mild symptoms; the combination of dyspnea, cough, and fever was present in 53%. Lactate dehydrogenase (LDH) was elevated in 63%, hypoxemia (PaO2 < 75 mm Hg) was present in 57%. Findings on chest roentgenograms were normal in 39%, whereas 36% showed interstitial and 25% acinar infiltrates. These three radiographic groups represented an increasingly severe PCP, indicated by higher LDH levels and hypoxemia (both p < 0.05). In a multivariate logistic regression, normal roentgenograms were predicted by low LDH and low peripheral blood granulocytes (p < 0.005). Mortality within 3 weeks was only 4% and correlated with the severity of infiltrates (p < 0.05). Normal roentgenograms thus corresponded to an oligosymptomatic, less severe PCP. In immunodeficient HIV-infected patients, a normal chest roentgenogram does not exclude PCP and should not distract from attaining a definite diagnosis by examination of induced sputum or bronchoalveolar lavage.

Adult↗
PubMed1993

Impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic T cells.

After infection with some viruses that tend to persist, neutralizing antibodies are generated rather late, i.e., after 1 to 3 mo. This has been observed for HIV, Hepatitis B infection in man, or after infection with lymphocytic choriomeningitis virus (LCMV) in mice. In contrast, nonneutralizing antibodies to LCMV are generated by day 7 and reach high titers by day 10. This study attempts to evaluate reasons for late and low titered neutralizing antibody responses. After a primary infection with low doses (10(2) plaque forming units) of the poorly cytopathic LCMV-WE, neutralizing antibodies were rarely produced at detectable levels before days 60 to 120. In vivo depletion of CD8+ CTL led to a marked enhancement and acceleration of kinetics of the neutralizing antibody response. In contrast, nonneutralizing antibodies, including those specific for LCMV-GP carrying the neutralizing determinant, were detectable very early, i.e., 4 to 7 days after infection, with maximum titers usually by day 10 irrespective of the presence or absence of CTL. Mice completely lacking CD8+ T cells because of deletion by homologous recombination (CD8-/-) also exhibited neutralizing antibodies early by day 10 to 20, and by day 120 reached very high titers. The neurotropic isolate LCMV-ARMSTRONG induced low but significant titers of neutralizing antibodies relatively early (i.e., by days 7 to 10), whereas the lympho-viscerotrope mutant virus LCMV-ARMSTRONG Cl-13 did not. Early and effective CTL responses causing immunopathology (and immunosuppression) correlated with the absence of neutralizing antibodies. The discrepancy between the CTL-dependent inhibition of neutralizing versus unimpaired anti-GP ELISA responses cannot be explained by different Ag doses alone. Additionally, it may reflect different kinetics of the responses, whereby the later neutralizing responses possibly requiring IgG affinity maturation may be more susceptible to general immunosuppression; also B cells expressing neutralizing receptors, but not those with antibodies binding GP (or NP), may be actively infected, therefore they present viral peptides on class I MHC Ag and may become targets for anti-LCMV-specific CTL.

Animals↗
PubMed1993

Lysis of infected cells in vivo by antiviral cytolytic T cells demonstrated by release of cell internal viral proteins.

Immunocompetent adult mice infected with lymphocytic choriomeningitis virus (LCMV) generate a strong antiviral cytotoxic T cell response that clears virus from all organs. Although there is good evidence that immune cytotoxic T lymphocytes (CTL) kill target cells in vitro, in vivo it is debated whether antiviral activity of CD8+ T cells is mediated via direct target cell lysis or via soluble mediators. To demonstrate CD8+ T cell-mediated destruction of infected cells in vivo a specific cell-internal releasable marker was used as label, i.e. the nucleoprotein (NP) of LCMV. Since LCMV is non-cytopathic the viral NP will only be released in substantial amounts because of destruction of infected host cells by immune CTL. It is shown here that the amount of NP released from infected and 51Cr-labeled target cells in vitro correlated well with the amount of radioactivity released. Viral NP released in vivo by CTL is bound and masked by the anti-NP antibodies that are produced very early and efficiently. However, NP could readily be detected in sera of LCMV-infected CD8+ competent mice that could not generate antibodies specific for the NP because they were treated with a depleting anti-CD4 antibody. NP was also detected in the cerebrospinal fluid of mice suffering from CD8+ T cell-mediated lymphocytic choriomeningitis after intracerebral infection. NP titers in sera of anti-CD4-treated LCMV-infected mice exhibited a peak around day 7-8 when CTL activity was highest. When mice were CD8 T cell-depleted with anti-CD8 monoclonal antibody or in LCMV-carrier mice, no NP was detected in the serum. Highly activated LCMV-specific CTL adoptively transfused to LCMV-infected irradiated recipient mice also caused a time-dependent release of NP into serum. This confirms that the CD8+ population is responsible for the release of NP from infected host cells. These results represent an in vivo correlate of CTL-mediated cytolysis and evidence that antiviral cytotoxic T cells are cytolytic in vivo. They also suggest that antibody responses to internal antigens of non-cytopathic viruses may signal CD8+ T cell-mediated destruction of infected host cells.

Animals↗
PubMed1993

Enhancement of disease by neutralizing antiviral antibodies in the absence of primed antiviral cytotoxic T cells.

The effects of neutralizing antibodies on the disease course in mice infected with the noncytopathic lymphocytic choriomeningitis virus (LCMV) were evaluated. Whereas non-neutralizing antisera exhibiting high enzyme-linked immunosorbent assay titers had no effect on T cell responses and their consequences, neutralizing antisera modulated them variably. Neutralizing antibodies were able to prevent lethal choriomeningitis after intracerebral infection with a neurotropic LCMV-isolate (ARMSTRONG) although they could not control local virus replication. The same antibodies exhibited little or no protective effect on choriomeningitis induced by LCMV-WE, a viscerotrope isolate. Surprisingly, these antibodies rendered mice much more susceptible to choriomeningitis after intracerebral infection with LCMV DOCILE, a very rapidly spreading lymphocyto-viscerotrope virus; in this situation antibodies prevented overwhelming infection which causes deletion of immunopathogenic cytotoxic T cell responses. Thus preexisting neutralizing antiviral antibodies had little influence on local virus spread in peripheral tissues but they reduced hematogenic spread and infection of antigen-presenting cells; thereby they influenced the primary cytotoxic T cell (CTL) response and indirectly modulated the extent of T cell-mediated immunopathology in peripheral organs. These results may explain why vaccines inducing neutralizing antibodies but no CTL may enhance an immunopathological disease caused by challenge infection with a noncytopathic virus.

Animals↗
PubMed1992

Vaccination with a synthetic peptide modulates lymphocytic choriomeningitis virus-mediated immunopathology.

Vaccination with a nucleopeptide (NP 118; amino acids 118 to 132) representing a cytotoxic T-cell epitope of lymphocytic choriomeningitis virus (LCMV) can modulate immunopathology. Immunization with NP 118 protected H-2d mice against intracerebral infection with the LCMV-ARMSTRONG isolate. However, when NP 118-primed H-2d mice were challenged intracerebrally with an intermediate dose (5 x 10(4) PFU) of the LCMV-DOCILE strain, all mice primed with NP 118 emulsified in incomplete Freund's adjuvant died, whereas unprimed mice survived. Correspondingly, peptide vaccination enhanced specifically the cytotoxic T-cell response, influencing the critical balance between T-cell response and virus spread.

Animals↗
PubMed1991

[HIV infection and syphilis. Case description and literature review].

Recent case reports emphasize that HIV infection may influence the clinical picture, course and therapy of concurrent syphilis. The case of a 32-year-old patient with coinfection by T. pallidum and HIV is presented. Clinical presentation, diagnostic procedures and therapy are discussed in the light of the current literature. False negative serologic tests for syphilis in HIV-patients raise the question of the sensitivity of these tests in HIV infection. Efficacy of therapy for neurosyphilis and the value of CSF (cerebrospinal fluid) examination in early syphilis are of increased importance in HIV infection. Current guidelines for diagnosis and therapy of syphilis in HIV patients are outlined.

AIDS Serodiagnosis↗
PubMed1991

Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24- or 96-well plates.

Titers of lymphocytic choriomeningitis virus (LCMV) were determined on adherent fibroblast cell lines in 24- or 96-well plates. After absorption of virus by cells and 48 h incubation under a methylcellulose overlay, cell monolayers were fixed with 4% formaldehyde in phosphate-buffered saline, permeabilized by incubation in 0.5% Triton X-100 in balanced salt solution and then stained with a monoclonal rat anti-LCMV and a peroxidase-labeled second stage antibody. The sensitivity of the assay is within a factor of 2-4 of conventional plaquing methods. The method also detects poorly or non-plaquing LCMV isolates, and therefore drastically reduces the need for titration of LCMV in mice. The method is quicker (2-3 days), as compared to conventional methods (4-6 days) and less expensive in terms of work and materials.

Animals↗
PubMed1991

Exploring the doctor-patient relationship reduces staff stress and enhances empathy when caring for AIDS patients.

At our AIDS outpatient clinic we presently care for more than 1,200 HIV-infected patients. All physicians in this unit have participated for 1 year in a case work group supervised by a liaison psychiatrist. The doctor-patient relationship, the assessment in the case work group and the ensuing influence on perception and behavior are demonstrated by 3 cases. Different issues challenge the doctor-patient relationship: the serious prognosis of predominantly young AIDS patients; isolation and stigmatization of patients; fear of contagion, and questions of confidentiality regarding contact tracing. Reflection upon the doctor-patient relationship improves communication skills and increases empathy towards AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Calcium carbonate for the treatment of hyperphosphatemia in chronic hemodialysis patients].

Hyperphosphatemia in chronic hemodialysis patients is usually treated with aluminium containing phosphate binders. In recent years there has been increasing evidence of serious complications due to aluminium accumulation. We have investigated a new calcium carbonate preparation with an HCl-resistant capsule designed to prevent gastrointestinal side effects. Its phosphate binding capacity in comparison to aluminium chloride hydroxide was investigated in 17 chronic hemodialysis patients. The dose of the phosphate binder was adjusted regularly so that the serum phosphorus levels were below 1.8 mmol/l. The mean dose of aluminium chloride hydroxide was 3.36 g/day and of calcium carbonate 4.96 g/day. The mean (+/- SD) serum calcium level was 2.58 +/- 0.11 mmol/l under aluminium chloride hydroxide and 2.50 +/- 0.25 mmol/l under calcium carbonate. The mean phosphorus level was 1.69 +/- 0.31 mmol/l under aluminium chloride hydroxide and 1.71 +/- 0.33 under calcium carbonate. Serum aluminium fell from 64.5 +/- 14.4 micrograms/l to 28.5 +/- 17.5 micrograms/l after 3 months.

Adult↗
PubMed1989

[Pneumothorax as a complication of Pneumocystis carinii pneumonia].

A pneumothorax occurred in a 29-year-old HIV-positive woman with rapidly progressive dyspnoea at rest and left-thoracic pain, dry cough and fever. Sputum test revealed Pneumocystis carinii pneumonia. Treatment was started with 20 mg/kg trimethoprim and 100 mg/kg sulfamethoxazole, but was poorly tolerated and changed for pentamidine, 4 mg/kg i.v. from the fifth day onwards. A chest drain was inserted, but pleurodesis became necessary after two further lung collapses. After three weeks secondary prophylaxis of the Pn. carinii pneumonia was started with pentamidine inhalations (60 mg every two weeks). The patient gradually improved under this regimen. Pneumothorax is a rare complication of Pn. carinii pneumonia, but should be considered in patients with rapid respiratory deterioration. In addition, Pn. carinii pneumonia should be considered in HIV-positive patients with pneumothorax.

Adult↗
PubMed1989

[Acute digitoxin poisoning].

We report a case of severe digitoxin poisoning with--as to our knowledge--the highest plasma concentration reported so far (376 ng/ml). On admission, the patient suffered from nausea and vomiting. The ECG showed a complete AV-block which was managed temporarily by pacing. Phenytoin was given for ventricular tachycardias. The plasma potassium level was 7.4 mmol/l. The elimination of the digitoxin was enhanced with cholestyramine and hemoperfusion. Because of persisting arrhythmias, hyperkalemia and a very high digitoxin level, purified Fab fragments of digoxin-specific antibodies (cross-reacting with digitoxin) were administered. After a first dose of 480 mg nausea disappeared readily, and with a second dose of 480 mg cardiac rhythm disturbances and hyperkalemia were overcome. There were no adverse reactions to treatment. We confirm the effectiveness of digoxin-specific Fab antibody fragments in life-threatening digitoxin intoxication.

Adult↗
PubMed1988

Mediastinal Hodgkin's disease--a retrospective analysis.

Thirty-seven patients with mediastinal Hodgkin's disease treated from 1972 to 1982 at the Division of Oncology of Basel University Hospital were analyzed retrospectively for their characteristics and the influence of various prognostic factors on survival. Deceased patients were older (35 vs. 25 years) and more often had systemic symptoms (8/22 vs. 3/15). 44% of the patients presented with mediastinal bulk disease, 66% of whom are in remission. No statistically significant influence of sex and stage was evident on the outcome. Patients treated with multimodality therapy had a significantly better survival than patients treated with radio- or chemotherapy only. No significant difference was found in survival in comparison to the population without mediastinal involvement.

Adolescent↗