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Biomedical subjects

D Nadal

Publications and source records attributed to D Nadal.

At least 55 records · Page 3Linked to original sources
PubMed1998

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in viral meningitis: upregulation of MMP-9 and TIMP-1 in cerebrospinal fluid.

A hallmark of viral meningitis is the invasion of monocytes, lymphocytes and, in the initial phase of the disease, neutrophils into the subarachnoidal space. By their degradation of different macromolecular components in the extracellular connective tissue, matrix metalloproteinases (MMPs) may be essential for the breakdown of the vessel wall in the meninges and the choroid plexus. In this study, the occurrence of MMP-1, MMP-2, MMP-3 and MMP-9 and the two tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2, was monitored in the cerebrospinal fluid (CSF) from patients with viral meningitis. Of the proteinases, MMP-9 was found in 13 of 39 (33%) patients, but not in controls; the levels being correlated with the neutrophil cell number in CSF. The CSF concentration of TIMP-1 was increased three-fold compared to the control group (median 233 ng/ml; range 9.4-1252.5 ng/ml) and was correlated to the levels of total protein in CSF. Of the other MMPs and TIMPs assayed, MMP-2 and TIMP-2 were constitutively expressed and not upregulated in viral meningitis. High levels of MMP-9 and MMP-2, as measured by ELISA, was associated with high proteolytic activity detected in CSF by zymography. In conclusion, invasion of the leukocytes into the CSF compartment in viral meningitis may involve MMP-9, its proteolytic effect likely being controlled by expression of TIMP-1.

Adolescent↗
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↗
PubMed1998

IgM to Bartonella henselae in cat-scratch disease and during acute Epstein-Barr virus infection.

The diagnostic value of IgM to Bartonella henselae was evaluated in 20 children with cat-scratch disease (CSD) and controls consisting of 20 blood donors and 20 children with enlarged lymph nodes without CSD by two indirect immunofluorescence assays (IFA). One was based on B. henselae cocultivated with Vero cells (host cell-associated IFA), and the other on B. henselae grown on agar (host cell-free IFA). With the host cell-associated IFA, 18 of 20 children with CSD revealed IgM, whereas only 14 did so with the host cell-free IFA. Sera of two blood donors as well as sera from three children with enlarged lymph nodes without CSD showed also positive IgM to cell-associated B. henselae. This study reveals that the IFA applied had sensitivities of 70-90% and specificities of 87.5-100% for detecting IgM to B. henselae. Additionally, 20 patients with IgM to Epstein-Barr virus (EBV) capsid antigen were tested for IgM to B. henselae. Sera of 16 and 9 of these patients revealed IgM to B. henselae with the host cell-associated and the host cell-free IFA, respectively. Using Western blot these sera were demonstrated to react against linearized proteins of Vero cells and of B. henselae. Thus, since acute EBV infection may substantially reduce the specificity of B. henselae-specific IgM tests, we conclude that diagnosis of CSD should be confirmed by a significant IgG titer to B. henselae or by detection of this pathogen.

Animals↗
PubMed1998

Osteomyelitis and septic arthritis due to Citrobacter freundii and Haemophilus influenzae type b.

This report describes dual infection with Citrobacter freundii and Haemophilus influenzae type b causing septic arthritis and osteomyelitis of the elbow in a previously healthy 5-year-old boy. The patient was treated successfully with intravenous fosfomycin for 4 weeks. Infections with Citrobacter beyond the neonatal period are rare in paediatric patients. When Citrobacter spp. is isolated, coinfection with other bacterial pathogens should be considered.

Arthritis, Infectious↗
PubMed1998

[Familiar and new aspects of Epstein-Barr virus infection].

The Epstein-Barr virus (EBV) persists after primoinfection in the human host. Over 90% of the adult population carries EBV, which is mainly acquired during childhood or adolescence. The full-blown clinical picture is infectious mononucleosis. Complications are rare but manifold. Symptomatic treatment is sufficient in most instances. Tumors associated with EBV represent a problem of medical relevance especially in the immunocompromised.

Adolescent↗
PubMed1997

C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial meningitis and mediate chemotactic activity on peripheral blood-derived polymorphonuclear and mononuclear cells in vitro.

The appearance of polymorphonuclear and mononuclear leukocytes in the cerebrospinal fluid (csf) is an important hallmark of bacterial meningitis. Chemokines are candidate mediators of cell migration from blood into the subarachnoid space. Therefore, concentrations of C-X-C and C-C chemokines in the csf of patients with pyogenic meningitis were measured by ELISA. Highly significant elevations of chemokine levels in comparison with noninflammatory csf controls were found for IL-8 (median, 21.6 ng/ml; range, < 0.1 to 191.3), growth-related gene product alpha (median, 5.6 ng/ml; range, < 0.1 to 48.2), monocyte chemotactic protein-1 (median, 26.4 ng/ml; range, < 0.2 to 193.8), macrophage inflammatory protein-1 alpha (MIP-1 alpha; median, 1.8 ng/ml; range, < 0.5 to 18.0), MIP-1 beta (median, 10.6 ng/ml; range, < 0.3 to 84.4), but not for RANTES (regulated upon activation, normal T cell expressed and secreted). The csf of bacterial meningitis were chemotactic for neutrophils and mononuclear leukocytes. Correlation analysis demonstrated a strong association between individual chemokine levels and chemotactic activity mediated by csf. A significant reduction of neutrophil chemotaxis was obtained by anti-IL-8 and anti-growth-related gene product alpha Abs, and a reduction of mononuclear cell migration was achieved by a combination of anti-monocyte chemotactic protein-1, anti-MIP-1 alpha, and anti-MIP-1 beta Abs. Since no significant correlation was found between csf leukocyte counts and chemokine concentrations or chemotactic activity mediated by csf, additional factors influence the extent of pleocytosis in vivo.

Adult↗
PubMed1997

Chemotactic activity on mononuclear cells in the cerebrospinal fluid of patients with viral meningitis is mediated by interferon-gamma inducible protein-10 and monocyte chemotactic protein-1.

In viral meningitis the inflammatory response involves activated T cells and monocytes which are recruited into the subarachnoid space. To identify the chemotactic signals attracting the cells to the site of infection in the meninges, we measured the levels of two CXC chemokines, interferon-gamma (IFN-gamma) inducible protein (IP)-10 and monokine induced by IFN-gamma, four CC chemokines, monocyte chemotactic protein (MCP)-1, RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, as well as the cytokines interleukin (IL)-15 and IL-16 in the cerebrospinal fluid (CSF) of patients suffering from viral meningitis. The results point to an involvement of two chemokines, MCP-1 and IP-10, since (1) unlike the other cytokines, MCP-1 and IP-10 were present in 97% and 79% of the CSF, respectively, at concentrations sufficient to induce chemotaxis of mononuclear cells; (2) more than 90% of the CSF of viral meningitis induced chemotaxis of peripheral blood mononuclear cells (PBMC) and all of them induced chemotaxis of activated T cells, and (3) the CSF-mediated chemotaxis of PBMC was inhibited by anti-MCP-1 antibodies and chemotaxis of activated T cells was abolished by the combination of anti-MCP-1 and anti-IP-10 antibodies. Our data provide evidence that MCP-1 and IP-10 lead to accumulation of activated T cells and monocytes in the CSF compartment in viral meningitis.

Adolescent↗
PubMed1997

Evaluation of commercial slides for detection of immunoglobulin G against Bartonella henselae by indirect immunofluorescence.

Four commercial slides were compared with in-house slides for the detection of immunoglobulin G (IgG) against Bartonella henselae in 58 healthy persons from a rural region by an indirect immunofluorescence assay. MRL-BA slides (MRL Diagnostics, USA) and Virion slides (Virion, Switzerland) with agar-derived Bartonella henselae showed IgG titers of > or = 1:256 in 44.8% and 51.7%, respectively, whereas Bion slides (Bios, Germany), MRL-Vero slides (MRL Diagnostics), and in-house slides with cell-associated Bartonella henselae showed such titers in 3.4%, 5.1% and 3.4%, respectively. The MRL-Vero slides (Bartonella IgG substrate slides, MRL Diagnostics) were further evaluated with 26 patients with cat scratch disease, 20 patients with lymphadenopathy not due to cat scratch disease, 100 blood donors from an urban area, and 120 blood donors from a mixed urban/rural area. In our mixed urban/rural population the IgG titer of 1:256 had a sensitivity of 84.6% and a specificity of 93.4% for the serodiagnosis of cat scratch disease. Seroprevalence was higher in blood donors from the mixed area (50.8%) than from the urban area (37%). MRL-Vero slides were considered useful for the serodiagnosis of cat scratch disease by indirect immunofluorescence and have replaced our in-house system. However, patients with low IgG titers should be retested three to four weeks after initial sampling to demonstrate a possible rise of IgG titers in paired sera.

Antibodies, Bacterial↗
PubMed1997

The 30-bp deletion variant of Epstein-Barr virus-encoded latent membrane protein-1 prevails in acute infectious mononucleosis.

To assess the frequency of malignancy-associated 30-bp deletion variants of the latent membrane protein 1 (LMP-1) in benign conditions, a comparative sequence analysis was done using samples from 20 American children with acute infectious mononucleosis and 16 Swiss children with chronic tonsillar hyperplasia. The 30-bp deletion variant (LMP-1-del) was present in 66% of patients (12/20 with infectious mononucleosis and 12/16 with tonsillar hyperplasia). Two additional patients had a 3-bp deletion and an inframe insertion of 18 nucleotides, respectively. All but 1 isolate had numerous nonsilent point mutations. These data identify a hypervariable region within the C-terminus of LMP-1, in a domain required for maximal stimulation of NF-kappaB activity. These data demonstrate that LMP-1-del variants are frequent in acute infectious mononucleosis and tonsillar hyperplasia and identical to those observed in Epstein-Barr virus-associated AIDS-related lymphoma.

Acute Disease↗
PubMed1997

Diagnostic value of cerebrospinal fluid examination in children with peripheral facial palsy and suspected Lyme borreliosis.

Our objective was to determine the diagnostic value of CSF examinations in the diagnosis of neuroborreliosis in children with peripheral facial palsy (PFP). Paired serum and CSF samples from 21 children with PFP were investigated for antibody responses to Borrelia burgdorferi antigens using three different ELISA systems and one Western blot assay. Twenty of the children (95%) had detectable immunoglobin (Ig) M or IgG in the acute-phase serum, but discrepancies between serologic assays were noted in 33% for IgM and 22 to 50% for IgG. Intrathecal specific-antibody production was detected in five of the 20 seropositive children (25%). These five patients showed seroconversion in convalescent sera in at least one assay. Similar seroconversion suggesting recent infection with B. burgdorferi was observed in eight of the 10 children (80%) without intrathecal specific-antibody production, from whom convalescent serum samples could be obtained. All patients with intrathecal antibodies or seroconversion had shown lymphocytic pleocytosis in the acute phase of PFP. In the acute phase of PFP the detection of intrathecal production of antibodies to B. burgdorferi allows prompt diagnosis of neuroborreliosis. For patients with lymphocytic pleocytosis but no detectable intrathecal antibodies, analysis of convalescent serum may help to establish this diagnosis.

Adolescent↗
PubMed1997

Human immunoglobulin preparations suppress the occurrence of Epstein-Barr virus-associated lymphoproliferation.

Suppression of Epstein-Barr virus (EBV) lymphoproliferation by three commercial human immunoglobulin (hu-Ig) preparations, one enriched with immunoglobulin A (hu-IgA-IgG) and the other two containing more than 97% immunoglobulin G (hu-IgG) with anti-EBV antibodies was studied. All three human preparations suppress EBV-induced lymphoproliferation in vitro and reduce release of interleukin (IL)-6 and IL-10 dose-dependently, irrespective, however, of the titer of EBV-specific antibodies present. This result was unexpected. Human Ig also reduces human recombinant IL-6-induced lymphoproliferation in EBV-free cultures and augments low-dose human recombinant IL-10-provoked suppression. In vivo studies used mice with severe combined immunodeficiency (SCID), reconstituted with human tonsillar mononuclear cells, and then infected with EBV from B95-8-derived supernatants. Immediate injection of hu-Ig after EBV infection, if given only once, delayed, and if given every two or four weeks, abolished the induction of EBV-associated lymphomas. Delay of hu-Ig injection by 48 hours after infection was less effective. Hu-IgG was consistently more efficacious than hu-IgA-IgG. Under these conditions the best survival rates were obtained with sustained hu-IgG administrations every two weeks. Serum hu-IL-6 and hu-IL-10 were detectable only in lymphoma-bearing SCID mice. Hu-Ig treatment reduced the detectability of both cytokines. These results suggest that hu-Ig-with antibodies to EBV-may exert a beneficial treatment potential for EBV-induced lymphoproliferation in immunocompromised patients. The dependence of this suppressive effect of hu-Ig on specific anti-EBV antibodies in vivo remains to be resolved.

Animals↗
PubMed1996

[Acute otitis media with effusion: an overview of the pathogenesis and recommendations for therapy].

Otitis media is one of the most common diseases in infants and young children. A combination of important factors contributes to the pathogenesis of acute otitis media and otitis media with effusion. These are poor tubal function, the degree of mastoid pneumatization, nasopharyngeal colonization with pathogenic bacteria and viruses, the ascending infectious pathway along the Eustachian tube, the immune status of the host, allergic and environmental factors, and genetic predisposition. Only correct diagnosis and understanding of they underlying pathophysiology enables the clinician to target treatment of the various forms of otitis media. We review the current concepts regarding evaluation and management of the diseased child and focus on the indication and selection of antibiotic therapy, bearing in mind the resistance rate within Switzerland. Most patients can be treated medically. "Otitis prone" individuals and children suffering from chronic otitis media with effusion with documented hearing loss clearly benefit from surgical intervention. We analyze the different treatment modalities and present a step-wise treatment algorithm. Newer vaccination trials indicate immunogenic effects even in young infants and show promising results in experimental and clinical studies.

Acute Disease↗