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Biomedical subjects

J Schüpbach

Publications and source records attributed to J Schüpbach.

At least 19 recordsLinked to original sources
PubMed2006

No indication for activation of exogenous retroviruses in patients with renal allograft rejection.

AIM: Reactivation of latent BK virus in kidney-transplanted patients results in severe graft dysfunction. The role of retroviruses infecting also latently target cells is not investigated so far in this setting. We determined the presence or induction of retroviruses in sera of immunosuppressed patients with renal allografts at the timepoint of organ rejection or ongoing polyomavirus nephropathy. PATIENTS AND METHODS: Sera of patients with acute kidney rejection or polyomavirus nephropathy (n=25) and controls (n=8) were tested for reverse transcriptase activity by the ultrasensitive product enhanced reverse transcriptase (PERT) assay. In parallel, kidney biopsies were investigated for histological signs of kidney rejection or polyomavirus nephropathy confirmed by either immunofluorescence or immunohistochemistry. RESULTS: None of the investigated sera, specifically those of patients with ongoing BK virus nephropathy, indicated reverse transcriptase activity. CONCLUSION: Our results do not support the idea of the induction of known or unknown retroviruses in patients with kidney transplantation, even under highly immunosuppressive therapies.

Adult↗
PubMed2005

Elective neck dissection versus observation in primary parotid carcinoma.

OBJECTIVE: To evaluate the efficacy of elective neck dissection in the clinically negative neck of patients with primary carcinoma of the parotid gland. Study design and setting A retrospective analysis was undertaken at a university Department of Otorhinolaryngology-Head and Neck Surgery on 83 previously untreated patients with primary carcinoma of the parotid gland and a clinically negative neck. The reliability of fine needle aspiration cytology, frozen section, and the clinico-pathologic findings of patients with occult neck metastases were analyzed. The regional recurrence rate and the outcome were compared among 2 groups; one with elective neck dissection (N = 41) and one without elective neck dissection (N = 42). RESULTS: The diagnosis of malignancy was known preoperatively in 59 (71%) cases, the exact histologic tumor type in 36 (43%) and the grade in 37 (44%) of 83 cases. Occult metastases were detected in 8 (20%) of 41 cNO patients, in 5 cases associated with a high-grade and in 3 cases with a low-grade carcinoma. Recurrence of disease developed in 5 (12%) patients in the elective neck dissection group and in 11 (26%) patients in the observation group. All of the 7 neck recurrences occurred in the observation group. The 5-year actuarial and disease-free survival rate was 80% and 86% for patients with elective neck dissection and 83% and 69% for patients without neck dissection. Conclusion and significance A routine elective neck dissection is suggested in all patients with primary carcinoma of the parotid gland. The efficacy of elective neck dissection, nevertheless, has never been evaluated prospectively.

Biopsy, Needle↗
PubMed2004

[Bone anchored hearing aids (B.A.H.A.)].

Semi-implantable bone conduction hearing aids of the type Bone Anchored Hearing Aids (B.A.H.A.) consist of an external vibrator hearing aid that is attached to a titanium screw implanted in the mastoideal bone behind the ear by means of a transcutaneous connector. In this way sound waves are transmitted directly to the bones of the skull, from where they are conducted to the cochlea. The primary indication for a semi-implantable bone conduction hearing aid is hearing loss due to conduction failure that is not surgically correctable. This may be caused, e.g. by ear canal atresia and other malformations of the external auditory meatus and of the middle ear, by chronic ear infections or by persistent high grade conduction hearing impairment after radical mastoidectomy. Today B.A.H.A.'s largely replace the less convenient conventional bone conducting hearing aids as hearing glasses or hearing bands, in which a vibrator is pressed against the skull. In conduction hearing impairment on both ears B.A.H.A.'s can be implanted bilaterally and thus binaural hearing with sound source localisation are made possible. A novel application is in cases of unilateral deafness, where the device is implanted on the side of the deaf ear and the amplified sounds are transmitted through the skull to the side of the hearing ear. Here it serves as a substitute for a CROS hearing aid. In adults the implantation is performed under local anesthesia as an out-patient procedure. Implantation may be undertaken under general anesthesia on children after two years of age. In Berne, B.A.H.A. bone conduction hearing aids have been implanted in 112 patients (ages 2-82 years) in the past 13 years. The operations have proved simple and without intra-operative complications. The long-term post-operative incidence of complications was low. The transcutaneous screw caused only isolated cases of transient skin reactions or local infections. In 7% of cases, rejection of the implant or a traumatic loosening of the screw required a reimplantation procedure. Over 90% of patients reported themselves satisfied with their partially-implantable B.A.H.A. hearing aids.

Adolescent↗
PubMed2004

[SHCS and the laboratory diagnosis of HIV infection--from the development of the HIV Western blot to virus quantification and clinically relevant individual virus characterization].

The first reliable diagnostic tools for the diagnosis of HIV infection, Western blot and ELISA, were created 20 years ago in the U.S., using initially sera from AIDS patients diagnosed clinically in Switzerland. In Swiss laboratories the diagnosis of HIV infection today is established by using 4th generation screening tests which detect both antibodies and p24 antigen while in the doctor's surgery a rapid antibody assay is used. Confirmation in authorized confirmatory labs relies on a set of different minimal combinations of positive test results derived from both the first and second blood specimen. In patients with a confirmed diagnosis of HIV infection, two further principal questions arise concerning, on the one hand, the virus load and, on the other hand, some clinically relevant properties of the infecting virus (type or subtype, resistance against antiretroviral drugs). The paper starts with a personal flashback to the first days of HIV diagnostics and describes the sensible use of tests available today for answering the above-mentioned principal questions. Alternative methods which can be used when standard tests fail or appear unreliable are mentioned also.

Acquired Immunodeficiency Syndrome↗
PubMed2003

[25-year-old therapy naive patient with 3 class resistant HIV infection].

The wide use of potent antiretroviral therapy has significantly reduced mortality and morbidity in patients infected with the HI-Virus. Good individual tolerance and regular intake of an adequate drug regimen often lead to a substantial recovery of impaired immunologic function. In a substantial fraction of patients drug resistant virus is emerging. In the last decade transmission of such viruses to newly infected patients has been reported in several countries. Especially transmission of multidrug-resistant virus is of major concern. We report a case of a 25 year-old Swiss man with a newly diagnosed HIV-infection with a multidrug-resistant virus. In connection to this case we discuss the importance of resistance testing in newly diagnosed patients.

Adult↗
PubMed2002

Immunophilins and HIV-1 infection.

Peptides of the V3 loop of the HIV-1 envelope glycoprotein gp120 have been shown to bind with high affinity to the immunophilins cyclophilin (Cyp) A, CypB and the FK506-binding protein 12 (FKBP12) [10]. We investigated whether immunophilins affect HIV-1 infection by assuming they are able to bind to the V3 loop of gp120. T cells and peripheral blood mononuclear cells were infected with T-cell-tropic or macrophage-tropic HIV-1 strains, respectively, in the presence of different concentrations of immunophilins. P24 antigen ELISA and real-time PCR measurements demonstrated that exogenously added immunophilins do not influence HIV-1 infection. CypA is known to interact with the HIV-1 Gag polyprotein and to be incorporated into the virions. This incorporation can be prevented by cyclosporin A (CsA) resulting in a decreased yield of infectious virus, the mechanism of which is unknown. We measured a normal production of proviral DNA in the first round of infection in CsA treated cells but afterwards, infection was decreased if CsA was present. Pre-treatment of the HIV-1 inocula with CsA, blocking the function of virus-associated CypA, did not inhibit the ensuing yield of infection. We therefore may conclude that endogenous CypA exerts its action after reverse transcription but before virus maturation, probably during capsid formation. FK520, an immunosuppressor which binds to FKBP, had no effect on HIV-1 infection.

Cyclophilin A↗
PubMed2001

Antiretroviral treatment monitoring with an improved HIV-1 p24 antigen test: an inexpensive alternative to tests for viral RNA.

Monitoring of viral RNA has become indispensable for the management of HIV-1 infection, but is expensive. This study investigated whether a highly improved test for p24 antigen could serve as an alternative. Thirty-four patients enrolled during 1997 into two treatment studies were tested prospectively for viral RNA by the Roche HIV-1 Monitor and for p24 antigen using signal-amplification-boosted ELISA of heat-denatured plasma. P24 antigen was detectable in 75.8% of 178 samples and HIV RNA in 73.9% of 138 samples. The half-life of p24 antigen in the first phase of effective treatment was 1.6 +/-.4 days (RNA, 1.7 +/-.8). An apparent second, slower decay phase had a half-life of 42 +/- 16 days. Treatment failure occurred in 14 patients. Secondary treatment failures with RNA rebounds from undetectable levels to < or = 10(3) copies/ml in two patients with an undetectable viral load and 10(3) HIV RNA copies/ml, respectively, at baseline were not detected by p24 antigen but carried a low risk for secondary resistance mutations. The other 12 failures were on average detected 29 days earlier by p24 antigen than by RNA (P =.0204), owing to slightly more frequent testing for p24 than for RNA (2.7 vs. 2.4 tests). Average costs for p24 antigen testing up to a failure were only 20.5% of those for RNA (P <.0001). These results indicate that heat-denatured, amplification-boosted p24 antigen measurement can be used as a simple and inexpensive alternative to HIV RNA testing for monitoring treatment.

Adolescent↗
PubMed2001

Quantification of in vitro retroviral replication using a one-tube real-time RT-PCR system incorporating direct RNA preparation.

The methodological and logistic benefits gained from assessing in vitro antiretroviral replication using one-tube real-time RT-PCR procedures are currently diminished by a continuing need for prior RNA isolation. We now report a simple and inexpensive modification of a commercially available one-tube RT-PCR assay, consisting of detergent-based virus lysis in the presence of a ribonuclease inhibitor, which can be used to directly quantify retroviral RNA levels in culture supernatant. This approach circumvents the potential loss of RNA inherent to RNA-isolation procedures based on prior extraction and demonstrates a dynamic range of at least 4 logs. Using in vitro culture systems incorporating either HIV-1 or FIV, we show that this ability to isolate retroviral RNA directly during the RT-PCR process can provide an equivalent alternative to one of the more time and resource-consuming steps in quantifying in vitro retroviral RNA levels.

Animals↗
PubMed2001

Induction/activation and detection of occult viral agents present in mammalian cells.

Occult viral agents in cell cultures may include (i) known viruses present at a concentration too low for detection and (ii) unknown viruses. For maximal safety regarding adventitious agents, a strategy is proposed which involves cellular cloning of candidate cell substrates for vaccines. This will render occult viruses present in either all cells or none, thus greatly facilitating their detection. Known and unknown members of virus families known to establish latency are best detected by molecular methods based on broadly conserved sequences and low stringency conditions. The presence of retrovirus particles, known or unknown, in vaccine harvests can be excluded by the Product-Enhanced Reverse Transcriptase (PERT) assay which detects particle-associated reverse transcriptase with the sensitivity of nucleic acid amplification tests. Latent retroviruses can be activated by stimulation with halogenated pyrimidines and/or azacytidine. Endogenous proviruses with no release of particles are of no concern.

Animals↗
PubMed2000

Human immunodeficiency virus type 1 p24 concentration measured by boosted ELISA of heat-denatured plasma correlates with decline in CD4 cells, progression to AIDS, and survival: comparison with viral RNA measurement.

Human immunodeficiency virus type 1 (HIV-1) RNA and p24 antigen concentrations were determined in plasma samples from 169 chronically infected patients (median CD4 cell count, 140 cells/microL; range, 0-1500 cells/microL). p24 quantification involved heat-mediated immune complex dissociation and tyramide signal amplification-boosted ELISA, which has a diagnostic sensitivity similar to that of RNA quantification by a commercial polymerase chain reaction kit. In Cox's proportional hazard models adjusted for CD4 cell count, both RNA (P<.005) and p24 (P=.043) levels were significant predictors of progression to AIDS. Measurement of p24 was superior to measurement of RNA in the model for survival (P=.032 vs. P=.19). p24 level was a significant predictor of CD4 cell decline in models adjusted for CD4 cell counts and was superior or equivalent to RNA level, depending on the group analyzed. Stratification by CD4 cell counts at baseline showed that the superiority of p24 measurement was more pronounced at lower levels of CD4 cells (<200/microL). p24 level may be of interest as a simple and inexpensive predictive marker of disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Performance of five different assays for the quantification of viral load in persons infected with various subtypes of HIV-1. Swiss HIV Cohort Study.

Five methods for the assessment of plasma viral load (VL) were evaluated in 103 seropositive patients infected with various subtypes of HIV-1. The methods included three RNA-based assays (Amplicor Monitor 1.5, Quantiplex version 2.0, NucliSens), one ultrasensitive reverse transcriptase (PERT) assay and one "boosted" p24 antigen (Ag) enzyme immunoassay (EIA). Subtyping was based on sequencing in env. The sensitivities were, in decreasing order, Amplicor > PERT > p24 Ag > NucliSens > Quantiplex. The low sensitivity of NucliSens was related to the missing of several non-B (A, E, F, G) or recombinant strains, whereas that of Quantiplex did not depend on subtype. In the 1 group O sample and 4 group M samples, only PERT assay or p24Ag EIA produced a positive result. In the quantitative range, correlation was best between Amplicor and Quantiplex (r = 0.8848), fair between Amplicor and NucliSens (r = 0.7064) or PERT assay (r = 0.7266), lowest between Amplicor and p24Ag EIA (r = 0.3989). Amplicor underestimated VL in 1 subtype E sample. Thus, Amplicor performed best in terms of sensitivity (compared with all other assays) and accuracy (compared with NucliSens, PERT assay, and p24Ag) for non-B subtypes in group M samples. PERT assay appears useful for VL assessment in infections by group O or other highly divergent viruses.

HIV Infections↗
PubMed2000

Use of HIV-1 p24 as a sensitive, precise and inexpensive marker for infection, disease progression and treatment failure.

HIV RNA is an acknowledged marker of disease activity and predictive of progression, while the p24 antigen is considered unsuitable. This is at odds with the fact that viral pathogenesis is usually mediated by proteins. One might expect that p24, if analyzed properly, might even be superior to RNA. This hypothesis was investigated in clinical studies using a sensitive and precise p24 test (heat-mediated immune complex dissociation with signal amplification-boosted ELISA). This test was as sensitive and specific as the polymerase chain reaction (PCR) for viral RNA (200-400 copy detection), an overall better predictor of CD4 decline and survival, while RNA prevailed in predicting AIDS. The lower costs of p24 testing also permit a closer monitoring of patients with an earlier detection of anti-retroviral treatment failures.

Biomarkers↗
PubMed2000

[Epiglottitis--a pediatric disease?].

Epiglottitis, commonly described as a paediatric disease, also occurs in adults. Early diagnosis and immediate treatment are crucial because of the rapid and possibly lethal course of upper airway obstruction due to swelling. Initial treatment consists in securing the upper airway and in antibiotic treatment. Streptococci and, especially in children, Haemophilus influenzae b are the most common bacteria. Our study focused on clinical and epidemiological changes since children started to be vaccinated against Haemophilus influenzae b in Switzerland (1992). We reviewed patient histories of 31 adults and 88 children who were hospitalised with epiglottitis at the University Hospital of Berne between 1989 and 1999. Our findings show that the incidence of epiglottitis in children, a clinically, epidemiologically and bacteriologically homogeneous disease, has dramatically decreased. Epiglottitis in adults presents as a more heterogeneous disease without change since the beginning of the vaccination programme. Due to the variety of germs it is impossible to recommend vaccination for adults against Haemophilus influenzae b.

Adult↗
PubMed1999

High frequency of non-B subtypes in newly diagnosed HIV-1 infections in Switzerland.

HIV-1 subtypes were determined in newly diagnosed residents of Switzerland. Blood was anonymously collected from patients with a first confirmed positive HIV-1 test result. Viral DNA from the env V3-V5 region was amplified by nested polymerase chain reaction (PCR) and screened for subtype B by heteroduplex mobility assay. All amplicons not identified as B were sequenced. From November 1996 to February 1998, 206 samples were analyzed. Main transmission risks were unprotected heterosexual (55.7%) or homosexual (27.1%) sexual contact or intravenous drug use (12.9%). Subtype B dominated in patients of Swiss, other European, American, or Asian citizenship; particularly high frequencies were found in homosexuals (97%) and drug users (94%). Non-B subtypes including A, C, D, E, F, G, H, a possible B/F recombinant, and a sequence related to J were present in 28.2% (95% confidence interval [CI], 22.9%-35.0%). Non-B were frequent in African citizens (95%), heterosexually infected individuals (44%), and women (43%). Heterosexually infected Swiss males harbored non-B strains in 18% and females in 33%. The results document a change in the epidemiology of newly diagnosed HIV-1 infections in Switzerland: predominance of heterosexual transmission and a high frequency of non-B subtypes.

Adult↗
PubMed1999

Prospective evaluation of amplification-boosted ELISA for heat-denatured p24 antigen for diagnosis and monitoring of pediatric human immunodeficiency virus type 1 infection.

The performance in pediatric human immunodeficiency virus type 1 (HIV-1) infection of a signal-amplification boosted ELISA for HIV-1 p24 antigen in plasma after heat-mediated immune complex dissociation was prospectively compared with polymerase chain reaction-based procedures. Diagnostic sensitivity and specificity of the p24 antigen test were 100% and 99.2%, respectively. Quantification revealed RNA in 85.7% and p24 antigen in 87.4% of 230 samples from 25 infected children. Concentrations of these indices in individual samples correlated (P<.0001). Introduction or modification of antiretroviral treatment showed concordant responses of RNA and p24 antigen in 39 (90.7%) of 43 instances. The treatment-induced changes in concentrations of RNA were higher than those of p24 antigen in 11 instances. In 1 instance, however, the concentration change of p24 antigen was greater than that of RNA (P=. 002). Variation of RNA concentrations was more marked than that of p24 antigen (P=.002). The p24 antigen test was equivalent to PCR for diagnosing and monitoring pediatric HIV-1 infection.

Anti-HIV Agents↗
PubMed1998

Prevention of vertical HIV transmission: additive protective effect of elective Cesarean section and zidovudine prophylaxis. Swiss Neonatal HIV Study Group.

OBJECTIVE: To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV transmission. DESIGN: Prospective study. SETTING: Obstetric and paediatric clinics in Switzerland. PARTICIPANTS: Children of mothers with HIV infection identified before or at delivery. INTERVENTIONS: Routine use of elective Cesarean section for HIV-infected parturients by some Swiss centres since 1985. National recommendation for zidovudine prophylaxis in mid-1994. MAIN OUTCOME MEASURE: HIV infection status of children. RESULTS: In a cohort of 494 children born at least 6 months before the analysis date, 67 out of 414 children with known infection status were found to be infected, giving an overall transmission rate of 16.2% [95% confidence interval (CI), 13.0-18.51. Elective Cesarean section with intact membranes and without previous labour was associated with a lower transmission rate of 6% [odds ratio (OR), 0.29; 95% CI, 0.12-0.70; P = 0.006 versus other delivery modes]. Transmission rate was intermediate after spontaneous delivery or non-elective Cesarean section (18%), and higher after obstetric interventions (27%; test for trend, P < 0.001). Since mid-1994, 78% of all women with registered pregnancies have received some form of zidovudine prophylaxis. Transmission rate was reduced from 17 to 7% after any zidovudine exposure (OR, 0.4; 95% CI, 0.11-1.41). Combined use of elective Cesarean section and zidovudine resulted in a 0% transmission rate (none out of 31), compared with 8% (seven out of 86) after elective Cesarean section without zidovudine, 17% (four out of 24) after zidovudine alone, and 20% (55 out of 271) after no intervention. CONCLUSIONS: Elective Cesarean section and zidovudine prophylaxis appear to have an additive effect in the prevention of vertical HIV transmission.

Abortion, Induced↗