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Biomedical subjects

Stefan Gerber

Publications and source records attributed to Stefan Gerber.

At least 19 recordsLinked to original sources
PubMed2006

[Prophylactic HPV vaccine: "a giant leap for mankind and..." questions for our society!].

Cervical cancer remains a major public health problem in the world. The strong link between human papillomavirus (HPV) and cervical cancer brings us the opportunity to develop a prevention against HPV infection through vaccination. HPV 16 and 18 induce about 70% of all cervical cancer, so prophylactic vaccine must be focus on these types. Trails established a great safety of theses vaccines and the induction of high titer of antibodies. They provide about 100% of protection against persistent HPV 16/18 infection and associated high-grade dysplasia. HPV vaccine must be proposed to young women "HPV-naïve" before beginning of their sexual activity. But questions arise for our society: when to perform it, who would be on charge, inclusion of boys also, parental approval, adaptation of cervical screening and high cost.

Female↗
PubMed2006

Impact of weather and climate on the incidence of acute coronary syndromes.

BACKGROUND: First investigations of the interactions between weather and the incidence of acute myocardial infarctions date back to 1938. The early observation of a higher incidence of myocardial infarctions in the cold season could be confirmed in very different geographical regions and cohorts. While the influence of seasonal variations on the incidence of myocardial infarctions has been extensively documented, the impact of individual meteorological parameters on the disease has so far not been investigated systematically. Hence the present study intended to assess the impact of the essential variables of weather and climate on the incidence of myocardial infarctions. METHODS: The daily incidence of myocardial infarctions was calculated from a national hospitalization survey. The hourly weather and climate data were provided by the database of the national weather forecast. The epidemiological and meteorological data were correlated by multivariate analysis based on a generalized linear model assuming a log-link-function and a Poisson distribution. RESULTS: High ambient pressure, high pressure gradients, and heavy wind activity were associated with an increase in the incidence of the totally 6560 hospitalizations for myocardial infarction irrespective of the geographical region. Snow- and rainfall had inconsistent effects. Temperature, Foehn, and lightning showed no statistically significant impact. CONCLUSIONS: Ambient pressure, pressure gradient, and wind activity had a statistical impact on the incidence of myocardial infarctions in Switzerland from 1990 to 1994. To establish a cause-and-effect relationship more data are needed on the interaction between the pathophysiological mechanisms of the acute coronary syndrome and weather and climate variables.

Climate↗
PubMed2006

Fetal serum beta2-microglobulin as a marker for fetal infectious diseases.

OBJECTIVES: To evaluate whether fetal serum beta2-microglobulin could be used as a marker of fetal cytomegalovirus (CMV) or toxoplasmosis infection. METHODS: beta2-microglobulin was retrospectively assayed in fetal serum collected from 64 patients with maternal infectious seroconversion (toxoplasmosis in 49 cases, CMV in 15). Using a beta2-microglobulin cutoff of 5 mg/L, infection and control groups were compared. RESULTS: Fetal serum beta2-microglobulin was >5 mg/L (5.2-13.5 mg/L) in 12 of the 13 cases with proved fetal toxoplasmosis infection, indicating 90% sensitivity. In the 39 pregnancies with maternal seroconversion but no laboratory signs of fetal infection, fetal serum beta2-microglobulin was <5 mg/L, indicating 100% specificity. Fetal serum was >5 mg/L (6.3-32 mg/L) in 14 of the 15 cases with proved fetal CMV infection, indicating 93.3% sensitivity. Specificity cannot be evaluated because maternal serum is not routinely screened for CMV during pregnancy. CONCLUSIONS: Fetal serum beta2-microglobulin is a reliable marker of fetal CMV or toxoplasmosis infection, which can be used in ambiguous situations. Because this increase is not specific, fetal serum beta2-microglobulin would potentially be raised in other fetal infections.

Biomarkers↗
PubMed2005

Intrauterine growth restriction and absent or reverse end-diastolic blood flow in umbilical artery (Doppler class II or III): A retrospective study of short- and long-term fetal morbidity and mortality.

OBJECTIVE: Absent or reverse end-diastolic flow (Doppler II/III) in umbilical artery is correlated with poor perinatal outcome, particularly in intrauterine growth restricted (IUGR) fetuses. The optimal timing of delivery is still controversial. We studied the short- and long-term morbidity and mortality among these children associated with our defined management. STUDY DESIGN: Sixty-nine IUGR fetuses with umbilical Doppler II/III were divided into three groups; Group 1, severe early IUGR, no therapeutic intervention (n = 7); Group 2, fetuses with pathological biophysical profile, immediate delivery (n = 35); Group 3, fetuses for which expectant management had been decided (n = 27). RESULTS: In Group 1, stillbirth was observed after a mean delay of 6.3 days. Group 2 delivered at an average of 31.6 weeks and two died in the neonatal period (6%). In Group 3 after a mean delay of 8 days, average gestational age at delivery was 31.7 weeks; two intra uterine and four perinatal deaths were observed (22%). Long-term follow-up revealed no sequelae in 25/31 (81%) and 15/18 (83%), and major handicap occurred in 1 (3%) and 2 patients (11%), respectively, for Groups 2 and 3. CONCLUSION: Fetal mortality was observed in 22% of this high risk group. After a mean period of follow-up of 5 years, 82% of infants showed no sequelae. According to our management, IUGR associated with umbilical Doppler II or III does not show any benefit from an expectant management in term of long-term morbidity.

Adult↗
PubMed2005

Association between fetal interleukin-1 receptor antagonist gene polymorphism and unexplained fetal death.

OBJECTIVE: In spite of extensive clinical examinations or autopsies, as many as 15% to 40% of stillbirths remain unexplained. A systemic fetal inflammatory response is an independent risk factor for severe neonatal morbidity, mediated by proinflammatory cytokines. As a major anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra) plays a crucial role modulating the proinflammatory response. The gene coding for IL-1ra (IL1RN) is polymorphic. We hypothesized that fetal possession of a specific allele, IL-1RN*2, associated with increased proinflammatory responses, may increase susceptibility to intrauterine fetal death. STUDY DESIGN: Fetal kidney cells were obtained from paraffin blocks of 27 unexplained stillbirths. DNA was isolated and tested for IL-1RN genotypes by polymerase chain reaction. As a control group, DNA from 302 live births was also tested. RESULTS: There was an enhanced rate of IL-1RN*2 homozygocity, 41%, among unexplained stillbirths compared with the control group, 8.6% (P < .001). Histologic analysis of fetal tissues demonstrated a predominant proinflammatory response in IL-1RN*2 homozygote fetuses. Extensive screening (microbiology, maternal serology, placenta histology) did not identify any specific trigger agent. CONCLUSION: There is an association between unexplained stillbirth and fetal homozygous IL1RN*2 carriage.

Adult↗
PubMed2004

ARB: a software environment for sequence data.

The ARB (from Latin arbor, tree) project was initiated almost 10 years ago. The ARB program package comprises a variety of directly interacting software tools for sequence database maintenance and analysis which are controlled by a common graphical user interface. Although it was initially designed for ribosomal RNA data, it can be used for any nucleic and amino acid sequence data as well. A central database contains processed (aligned) primary structure data. Any additional descriptive data can be stored in database fields assigned to the individual sequences or linked via local or worldwide networks. A phylogenetic tree visualized in the main window can be used for data access and visualization. The package comprises additional tools for data import and export, sequence alignment, primary and secondary structure editing, profile and filter calculation, phylogenetic analyses, specific hybridization probe design and evaluation and other components for data analysis. Currently, the package is used by numerous working groups worldwide.

Data Display↗
PubMed2004

Mycoplasma hominis in mid-trimester amniotic fluid: relation to pregnancy outcome.

OBJECTIVE: The relationship between detection of Mycoplasma hominis in mid-trimester amniotic fluid and subsequent pregnancy outcome was investigated. STUDY DESIGN: Amniotic fluids from 456 women of European background who underwent a transabdominal amniocentesis at weeks 15-17 of pregnancy were tested for M. hominis by polymerase chain reaction (PCR). The amplicons were hybridized to an internal probe and detected by ELISA. Pregnancy outcomes and clinical data were subsequently obtained. RESULTS: M. hominis were identified in 29 (6.4%) of the amniotic fluids. The rate of preterm labor in women positive for M. hominis (14.3%) was higher than in the negative women (3.3%) (p=0.01). Similarly, a spontaneous preterm birth with intact membranes occurred in 10.7% of the M. hominis-positive women as opposed to only 1.9% of the negative women (p = 0.02). The presence of this mycoplasma was not correlated with fetal chromosomal aberrations, intrauterine growth restriction or preeclampsia. CONCLUSIONS: Detection of M. hominis in second-trimester amniotic fluids can identify women at increased risk for subsequent preterm labor and delivery.

Adult↗
PubMed2003

Screening for infectious diseases.

INTRODUCTION: Fetal brain injury is an essential cause of lifelong morbidity. Infection appears as a cause of brain damage. Apart from chorioamnionitis, screening for infectious diseases must be considered in pregnancies with a risk of congenital infection or cases with abnormal cerebral ultrasound findings. DISCUSSION: Congenital infections include most of the major components of the TORCH complex: toxoplasmosis, rubella, cytomegalovirus, herpes, and varicella. Seronegative mothers can develop primary infection, which carries a risk of vertical transmission. The timing of the infection is a critical point, because fetal damage often depends on the gestational age at which acute maternal infection took place and occurs more likely in the first half of pregnancy. Antenatal ultrasound can detect brain abnormalities, like hydrocephalus, periventricular leukomalacia, calcifications or hemorrhage. Maternal serologic tests must be performed to look for an infectious etiology; the most frequent agents are the components of the TORCH complex. But additional serology must include parvovirus B19, HIV, and coxsackieviruses.

Brain Injuries↗
PubMed2003

Interleukin-1beta gene polymorphism in women with vulvar vestibulitis syndrome.

OBJECTIVE: The pathogenesis of vulvar vestibulitis syndrome remains unknown but may be related to a localized chronic inflammation. The relation between this syndrome and a polymorphism at position +3953 in the interleukin-1beta gene was examined. Allele 2 of this gene has been associated with increased pro-inflammatory immunity. STUDY DESIGN: Buccal or vestibular swabs from 59 women with strictly defined vulvar vestibulitis and from 48 healthy women were tested by polymerase chain reaction for the presence of two alleles at the +3953 interleukin-1beta locus. RESULTS: Allele 2 of the interleukin-1beta gene was identified in 27 (46%) women with vulvar vestibulitis as opposed to 12 (25%) control women (P=0.03). The interleukin-1beta 1,1 genotype was present in 36 (75%) controls as opposed to 32 (54%) vulvar vestibulitis syndrome patients (P=0.02). All subjects had been previously tested for induced interleukin-1beta production in response to bacterial lipopolysaccharide. In both patients and controls, possession of allele 2 was associated with a small but non-statistically significant increase in induced interleukin-1beta production. CONCLUSION: Allele 2 in the interleukin-1beta gene is more common in women with vulvar vestibulitis syndrome than in other women. Susceptibility to vulvar vestibulitis syndrome might be influenced by carriage of this polymorphism.

Alleles↗
PubMed2003

Detection of Ureaplasma urealyticum in second-trimester amniotic fluid by polymerase chain reaction correlates with subsequent preterm labor and delivery.

Ureaplasma urealyticum is the microorganism most frequently isolated from the amniotic fluid of women in preterm labor. The relationship between intra-amniotic U. urealyticum in healthy second-trimester pregnant women and subsequent pregnancy outcome was investigated. Transabdominal amniotic fluid obtained from 254 asymptomatic women at 15-17 weeks' gestation were tested by polymerase chain reaction (PCR). U. urealyticum was identified in 29 subjects (11.4%). A subsequent preterm labor occurred in 17 U. urealyticum-positive women (58.6%), compared with 10 (4.4%) U. urealyticum-negative women (P<.0001). Preterm birth was documented in 7 (24.1%) U. urealyticum-positive women compared with only 1 U. urealyticum-negative woman (0.4%) (P<.0001). U. urealyticum-positive women also had a higher prevalence of preterm labor in a prior pregnancy (20.7%) than did the negative women (2.7%; P=.0008). PCR testing of second-trimester amniotic fluid for U. urealyticum can identify women at risk for subsequent preterm labor and delivery.

Adult↗
PubMed2003

Polymorphism in intron 2 of the fetal interleukin-1 receptor antagonist genotype influences midtrimester amniotic fluid concentrations of interleukin-1beta and interleukin-1 receptor antagonist and pregnancy outcome.

OBJECTIVE: Preterm labor in experimental models is initiated by intra-amniotic interleukin-1beta (IL-1beta) and inhibited by interleukin-1 receptor antagonist (IL-1ra). The IL-1ra gene is polymorphic and the different alleles are associated with variations in IL-1beta and IL-1ra production. The relationship among the IL-1ra genotype of the fetus, concentrations of IL-1beta and IL-1ra in second-trimester amniotic fluid, and pregnancy outcome was determined. STUDY DESIGN: Amniotic fluids from 291 consecutive women with singleton pregnancies, obtained at 15 to 17 weeks' gestation, were tested for IL-1beta and IL-1ra concentrations by enzyme-linked immunosorbent assay. DNA from fetal cells was analyzed for a length polymorphism in intron 2 of the IL-1ra gene by polymerase chain reaction. Pregnancy outcomes were obtained after completion of testing. RESULTS: The distribution of fetal IL-1ra genotypes was similar to that found in other populations: 50.9% (148) were homozygous for allele 1 (IL1RN*1), 39.5% (115) were IL1RN*1/allele 2 (IL1RN*2) heterozygotes, 6.9% (20) were IL1RN*2 homozygotes, whereas 2.7% (8) had combinations of other alleles. Fetal possession of IL1RN*2 was associated with a greater than 50% increase in midtrimester intra-amniotic IL-1beta levels (P=.006) and a smaller increase in IL-1ra levels (P=.01) compared with fetuses who were IL1RN*1 homozygotes. Despite the low sample size, IL1RN*2 homozygosity, but not midtrimester intraamniotic levels of IL-1beta and IL-1ra, was related to an increased rate of preterm birth (P<.0001). In the 11 pregnancies that were subsequently terminated because of major malformations, there was a decreased frequency of IL1RN*1 homozygosity (P=.04). Birth weight was unrelated to IL-1ra genotype. CONCLUSION: Possession by the fetus of the IL1RN*2 allele is associated with enhanced intraamniotic IL-1beta production. Induction of an intra-amniotic proinflammatory immune response might be more likely to lead to preterm labor in fetuses carrying the IL1RN*2 allele.

Amniotic Fluid↗
PubMed2003

Interleukin-1 receptor antagonist gene polymorphism, vaginal interleukin-1 receptor antagonist concentrations, and vaginal ureaplasma urealyticum colonization in pregnant women.

Ureaplasma urealyticum is the microorganism most frequently isolated from amniotic fluids of women in preterm labor. The relationship between vaginal colonization with U. urealyticum, vaginal interleukin-1 receptor antagonist (IL-1ra) levels, and the IL-1ra genotype in pregnant women was examined. Vaginal specimens, obtained with a cotton swab from 207 women in their first trimester of pregnancy, were tested for IL-1ra concentrations by enzyme-linked immunosorbent assay and for U. urealyticum and IL-1ra genotypes by PCR. U. urealyticum was detected in 85 (41.1%) women. The median IL-1ra level was 450 ng/ml in women positive for U. urealyticum, as opposed to 225 ng/ml in women negative for this microorganism (P < 0.0001). Sixty-two percent of the 16 women who were homozygous for allele 2 of the IL-1ra gene (IL-1RN*2) were colonized with U. urealyticum, as opposed to 47% of the 49 women who were IL-1RN*1/IL-1RN*2 heterozygotes and 34% of the 133 women who were IL-1RN*1 homozygotes (P < 0.05). Median IL-1ra levels were 750 ng/ml in IL-1RN*2 homozygotes, 300 ng/ml in IL-1RN*1/IL-1RN*2 heterozygotes, and 250 ng/ml in IL-1RN*1 homozygotes (P = 0.02). The vast majority of subjects had an uneventful pregnancy and delivered a healthy infant at term. The IL-1ra genotype or U. urealyticum colonization was unrelated to birth weight. Pregnant women who are colonized with U. urealyticum during the first trimester have elevated vaginal IL-1ra concentrations and a higher prevalence of the IL-1RN*2 homozygote genotype than do noncolonized women.

Adolescent↗
PubMed2002

Long-term ex vivo expansion of human fetal liver primitive haematopoietic progenitor cells in stroma-free cultures.

Successful expansion of haematopoietic cells in ex vivo cultures will have important applications in transplantation, gene therapy, immunotherapy and potentially also in the production of non-haematopoietic cell types. Haematopoietic stem cells (HSC), with their capacity to both self-renew and differentiate into all blood lineages, represent the ideal target for expansion protocols. However, human HSC are rare, poorly characterized phenotypically and genotypically, and difficult to test functionally. Defining optimal culture parameters for ex vivo expansion has been a major challenge. We devised a simple and reproducible stroma-free liquid culture system enabling long-term expansion of putative haematopoietic progenitors contained within frozen human fetal liver (FL) crude cell suspensions. Starting from a small number of total nucleated cells, a massive haematopoietic cell expansion, reaching > 1013-fold the input cell number after approximately 300 d of culture, was consistently achieved. Cells with a primitive phenotype were present throughout the culture and also underwent a continuous expansion. Moreover, the capacity for multilineage lymphomyeloid differentiation, as well as the recloning capacity of primitive myeloid progenitors, was maintained in culture. With its better proliferative potential as compared with adult sources, FL represents a promising alternative source of HSC and the culture system described here should be useful for clinical applications.

Antigens, CD34↗
PubMed2002

A deficiency in interferon-alpha production in women with vulvar vestibulitis.

OBJECTIVE: Previous studies have suggested that interferon-alpha may be an effective treatment for some women with vulvar vestibulitis. We evaluated whether women with this syndrome had a deficiency in endogenous and induced interferon-alpha production. STUDY DESIGN: Blood was collected in heparinized tubes from 62 women with vulvar vestibulitis and 47 control women of similar age and ethnicity. Whole blood cultures were incubated in the presence of 0.1 ng/mL lipopolysaccharide (induced) or culture medium (uninduced) for 18 to 20 hours. Aliquots were tested for interferon-alpha levels by enzyme-linked immunosorbent assay. Vestibular samples were tested for human papillomavirus by polymerase chain reaction. Aliquots were also characterized for alleles of the polymorphic gene, interleukin-1 receptor antagonist, by polymerase chain reaction. RESULTS: In uninduced cultures, interferon-gamma was present in 68.1% of control subjects as opposed to 33.9% of vulvar vestibulitis patients ( P =.0005). Similarly, after lipopolysaccharide stimulation, 70.2% of control subjects and only 48.4% of patients produced interferon-alpha ( P =.03). Among the positive samples, however, there were no differences in the interferon-alpha levels between patients and control subjects. In contrast, induction of interferon gamma in response to lipopolysaccharide was similar in control subjects (78.0%) and vulvar vestibulitis patients (82.1%). Women who have a deficiency in interferon-alpha production did not have an increased prevalence of human papillomavirus infection. There was no relation between interleukin-1 receptor antagonist genotype and interferon-alpha production. CONCLUSION: An inability to produce interferon-alpha may contribute to chronic vestibular inflammation in some women.

Female↗
PubMed2002

Defective regulation of the proinflammatory immune response in women with vulvar vestibulitis syndrome.

OBJECTIVE: The cause of vulvar vestibulitis syndrome is unknown. To determine a possible role for defective immune regulation in this chronic condition, proinflammatory and anti-inflammatory immune responses to the 70-kd heat shock protein and to lipopolysaccharide were compared in women with and without vulvar vestibulitis syndrome. STUDY DESIGN: Whole blood cultures from 62 women with vulvar vestibulitis syndrome and 48 control subjects were incubated in the presence or absence of 5 microg/mL human recombinant 70-kd heat shock protein or 0.1 ng/mL lipopolysaccharide for 18 hours. The culture supernatants were then assayed for interleukin-1 beta and interleukin-1 receptor antagonist by enzyme-linked immunosorbent assay. RESULTS: Median levels of interleukin-1 beta were higher in response to heat shock protein in cultures from patients with vulvar vestibulitis syndrome (median, 1.07 ng/mL) as opposed to control subjects (median, 0.40 ng/mL; P =.006). Conversely, levels of interleukin-1 receptor antagonist were higher in response to heat shock protein in control subjects (median, 39.21 ng/mL) than in patients (median, 29.25 ng/mL; P =.009). In response to lipopolysaccharide, median levels of interleukin-1 beta were similar in patients (1.00 ng/mL) and control subjects (1.15 ng/mL); median interleukin-1 receptor antagonist concentrations were higher in control subjects (70.0 ng/mL) than in patients (44.3 ng/mL; P <.0001). The ratio of interleukin-1 receptor antagonist to interleukin-1 beta was higher in control subjects than in women with vulvar vestibulitis syndrome in response to both heat shock protein (P =.0002) and lipopolysaccharide (P =.01). In uninduced cultures, interleukin-1 receptor antagonist levels were also higher in control subjects (median, 1.60 ng/mL) than in patients with vulvar vestibulitis syndrome (median, 0.62 ng/mL; P <.0001). CONCLUSION: A relative inability to down-regulate proinflammatory interleukin-1 beta activity by interleukin-1 receptor antagonist may contribute to the pathophysiologic features of vulvar vestibulitis syndrome.

Cytokines↗
PubMed2002

Polymorphism in the interleukin-1 gene complex and spontaneous preterm delivery.

OBJECTIVE: We examined the association between preterm delivery and polymorphisms at position +3953 of the interleukin-1 beta gene (IL1B+3953) and in intron 2 of the interleukin-1 receptor antagonist gene (IL1RN). STUDY DESIGN: This was a case-control study that involved 52 pregnancies that resulted in spontaneous preterm delivery before 34 weeks of gestation and 197 pregnancies that resulted in birth at term. Polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Homozygous carriage of IL1B+3953 allele 1 by fetuses of African descent was associated with a risk of preterm delivery (P =.033). Fetuses of Hispanic descent that carried IL1RN allele 2 were found to be at an increased risk for preterm premature rupture of membranes and subsequent preterm delivery(P =.021; odds ratio, 6.5; 95% CI, 1.25-37.7). CONCLUSION: There are associations of spontaneous preterm delivery with the fetal carriage of IL1B+3953*1 and IL1RN*2 alleles in African and Hispanic populations, respectively.

Adult↗
PubMed2002

Differential characterization of women with vulvar vestibulitis syndrome.

OBJECTIVE: We differentiated women with vulvar vestibulitis syndrome into subgroups on the basis of the time of symptom onset, a history of recurrent vulvovaginal candidiasis, and the interleukin-1 receptor antagonist gene polymorphism. STUDY DESIGN: One hundred sixty-two consecutive patients with strictly defined vulvar vestibulitis syndrome were asked to fill out a questionnaire with the assistance of their gynecologist. A buccal sample was collected from each subject for the analysis of interleukin-1 receptor antagonist gene polymorphism; vaginal and vestibular microbial investigations were performed. RESULTS: Symptoms began with the first act of coitus in 20.4% of patients. A history of a recurrent Candida vulvovaginal infection was reported in 42.6% of patients; 25.9% of the patients were positive for the homozygous interleukin-1 receptor antagonist 2,2 genotype. Women with primary vulvar vestibulitis syndrome differed from women with secondary vulvar vestibulitis syndrome; women with primary vulvar vestibulitis syndrome were younger at the time of the onset of the symptoms (23.8 vs 31.2 years, P <.0001) and had never been pregnant (84.8% vs 61.2%, P <.0001). Women with a history of recurrent Candida vulvovaginitis differed from the other subjects by having a higher frequency of constant vestibular pain (40.6% vs 20.4%, P =.005), a vaginal discharge (79.7% vs 45.2%, P <.0001), and dysuria (62.3% vs 29.0%, P =.0001). Women who were homozygous for interleukin-1 receptor antagonist 2,2 genotype had an earlier onset of symptoms (26 years) than did women who were allele 1 homozygotes (31.3 years, P <.05). They also had a shorter duration of symptoms (4.1 vs 5.9 years, P <.05) and a higher frequency of allergy (47.6% vs 23.4%, P =.002). Human papillomavirus in the vaginal vestibule occurred at a greater frequency in women who were homozygous for interleukin-1 receptor antagonist 2,2 genotype. CONCLUSION: Subgroups of women with vulvar vestibulitis syndrome may be differentiated by symptomatic and genetic variables.

Adult↗