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Biomedical subjects

B Sölder

Publications and source records attributed to B Sölder.

At least 19 recordsLinked to original sources
PubMed1999

Lack of absorption of didanosine after rectal administration in human immunodeficiency virus-infected patients.

The feasibility of rectal administration of didanosine (DDI) was studied in six human immunodeficiency virus-infected patients. After oral intake of a DDI solution (100 mg/m2 of body surface area) combined with an antacid (Maalox), pharmacokinetic parametric values were in accordance with previously published data; the mean +/- standard deviation for terminal half-life was 59.5 +/- 15.0 min, that for peak concentration was 5.2 +/- 3.9 mumol/liter, and that for the area under the time-concentration curve (AUC) was 494 +/- 412 min.mumol/liter. After rectal administration of a similarly prepared DDI solution (100 mg/m2 of body surface area), plasma DDI levels were below the detection limit (0.1 mumol/liter) at all time points in five of the six patients, and in the remaining patient the AUC after rectal application was only 5% of that after oral administration. We conclude that oral administration of DDI cannot be easily replaced by rectal application.

Administration, Rectal↗
PubMed1998

Neopterin levels and pulmonary tuberculosis in infants.

Neopterin is produced and released by human macrophages in response to stimulation with interferon-gamma and changes in neopterin concentrations indicate cellular immune activation. Pulmonary infection with Mycobacterium tuberculosis is also associated with increased neopterin levels in body fluids. We report the clinical course, the diagnostic results, and the urinary neopterin levels of seven children (ages 10 months-6(6/12) years) with pulmonary tuberculosis. Two of them had progressive primary tuberculosis, in one case caused by isoniazid resistance. Diagnostic criteria included chest radiographs, intradermal tuberculosis skin testing, and culture of aspirated secretions for tuberculosis. Neopterin levels were determined by high performance liquid chromatography. The five patients with uncomplicated primary disease and a good response to therapy with isoniazid, rifampin, and pyrazinamide showed no or slightly elevated neopterin levels (mean, 458 micromol/mol creatinine). In the two patients with progressive primary tuberculosis we documented excessively high neopterin levels (mean, 2170 micromol/mol creatinine). We conclude that neopterin may be a useful parameter for measuring the degree of disease activity and the response to therapy.

Antitubercular Agents↗
PubMed1998

Fine localization of the Nijmegen breakage syndrome gene to 8q21: evidence for a common founder haplotype.

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, a birdlike face, growth retardation, immunodeficiency, lack of secondary sex characteristics in females, and increased incidence of lymphoid cancers. NBS cells display a phenotype similar to that of cells from ataxia-telangiectasia patients, including chromosomal instability, radiation sensitivity, and aberrant cell-cycle-checkpoint control following exposure to ionizing radiation. A recent study reported genetic linkage of NBS to human chromosome 8q21, with strong linkage disequilibrium detected at marker D8S1811 in eastern European NBS families. We collected a geographically diverse group of NBS families and tested them for linkage, using an expanded panel of markers at 8q21. In this article, we report linkage of NBS to 8q21 in 6/7 of these families, with a maximum LOD score of 3.58. Significant linkage disequilibrium was detected for 8/13 markers tested in the 8q21 region, including D8S1811. In order to further localize the gene for NBS, we generated a radiation-hybrid map of markers at 8q21 and constructed haplotypes based on this map. Examination of disease haplotypes segregating in 11 NBS pedigrees revealed recombination events that place the NBS gene between D8S1757 and D8S270. A common founder haplotype was present on 15/18 disease chromosomes from 9/11 NBS families. Inferred (ancestral) recombination events involving this common haplotype suggest that NBS can be localized further, to an interval flanked by markers D8S273 and D8S88.

Chromosome Breakage↗
PubMed1998

Comparison of two antiretroviral triple combinations including the protease inhibitor indinavir in children infected with human immunodeficiency virus.

OBJECTIVE: The effects of two antiretroviral triple combinations including the protease inhibitor indinavir on the surrogate markers, viral load and CD4 cells were evaluated. METHODS: Fifteen patients with high viral load or disease progression under their prior antiretroviral therapy were switched to zidovudine/lamivudine/indinavir (Group A, n = 10) or stavudine/lamivudine/indinavir (Group B, n = 5). Serial determinations of viral load and CD4 cells were performed. RESULTS: The median reduction of the viral load was 0.6 log after 3 months and 0.8 log after 6 months in Group A and 2.5 and 2.4 log after 3 and 6 months in Group B, respectively. After 3 and 6 months 3 of 10 patients in Group A and 3 of 5 patients in Group B had viral load reductions below the detection limit of the assay. Patients with an additional switch of nucleoside analogues at start of indinavir therapy (regardless of the specific reverse transcriptase inhibitor used) had significantly better reductions of the viral load than patients without such a switch (median 2.3 log vs. 0.2 log after 6 months, P < 0.05). In Group A the median of the relative increase of CD4 cells was 37% after 3 months and 57% after 6 months (P = 0.002); in Group B the medians of the relative increase of CD4 cells were 145 and 163% (not significant), respectively. Two patients from Group A and 1 from Group B developed renal calculi, which resolved after adequate hydration. One patient was withdrawn because of intractable vomiting attributed to indinavir. CONCLUSION: In a small cohort of HIV-infected pediatric patients with extensive prior antiretroviral treatment, triple therapy including indinavir had a sustained effect on the decrease of the viral load and the increase of CD4 cells similar to results obtained in antiretrovirally experienced adults. This effect was significantly better in patients with an additional switch of a nucleoside analogue at start of triple therapy with indinavir than in patients without such a change.

Adolescent↗
PubMed1998

Dyskeratosis congenita: multisystemic disorder with special consideration of immunologic aspects. A review of the literature.

Dyskeratosis congenita (DC) is a rare, predominantly X-linked multisystemic disorder. It demonstrates a wide spectrum of clinical manifestations and typically presents with dermatologic symptoms during the first decade of life. This review of the literature points out the importance of hematologic and immunologic alterations in defining the course and prognosis of the disease process. Pancytopenia as well as the humoral and cellular disturbances in immunologic functions associated with this disease complex may lead to severe infections that represent the main cause of death. The pathogenesis of DC is still unclear and a curative therapy is presently lacking. Recent reports suggest that a beneficial effect may be observed in the administration of hematopoietic growth factors (G-CSF, GM-CSF) for patients with DC and neutropenia.

Adolescent↗
PubMed1997

[Enterohemorrhagic Escherichia coli and hemolytic-uremic syndrome].

Enterohemorrhagic Escherichia coli (EHEC) are increasingly identified as the cause of diarrhea and hemorrhagic colitis in countries with highly developed livestock. In 5-10% of patients, full-blown hemolytic uremic syndrome (HUS) occurs as a postinfectious life-threatening complication. Up to 1996, 5 out of 39 patients (12.8%) with EHEC O157 infections in Austria developed HUS. Acute complications of HUS such as brain edema may also lead to death; one fatal outcome has been observed so far in Austrian patients. Aside from the cytotoxic Shiga toxins, other different pathogenic factors are often found in clinical EHEC isolates. These include a cytolysin termed EHEC-hemolysin and a low molecular heat-stabile enterotoxin. Furthermore, most EHEC strains express an important surface protein, intimin, which is important for adherence to intestinal epithelial cells. EHEC are heterogeneous in their antigenic structure (O-, H-antigens). In Austria O157:H7 and O157:H- are the dominating serogroups; in 1997 the first Austrian case of HUS due to EHEC O26:H11 was documented. Because there are no known reliable phenotypical markers for EHEC, diagnostic strategies should focus on the demonstration of Shiga toxins or Shiga toxin genes. For epidemiological purposes it is also important to attempt to isolate the causative agent. Cows and other ruminants are reservoirs for EHEC. In the Tyrol 3% of unpasteurised milk samples, up to 10% of minced beef samples, and 6% of calves yield EHEC O157. Aside from transmission via contaminated food, direct transmission from person to person also plays a major role in the chain of EHEC infection. In contrast to Italy and Bavaria, Austria has not experienced a major outbreak due to this organism so far. A nationwide surveillance system of HUS has shown an incidence of 0.37 HUS cases per 100,000 residents in the age group 0-14 years for 1995 (Italy: 0.2 cases per 100,000; Bavaria: approx. 1.5 cases per 100,000).

Animals↗
PubMed1997

Surgical treatment of bacillus Calmette Guérin lymphadenitis.

Although its protective effect is contested and the risk of contracting tuberculosis is rather low nowadays, BCG vaccination is frequently performed. Changes of strain repeatedly led to an increased complication rate. In Austria between 1990 and 1991, of 3386 newborn babies (Strain Pasteur) 116 developed lymphadenitis 3 to 28 weeks after vaccination. The affected children received four types of treatment: nothing specific, isoniazid, or surgery with and without isoniazid. Surgical treatment was found to be necessary in 96 cases. Bacilli were successfully grown in culture in 46% of cases up to week 20 after vaccination; but later than 20 weeks no culture became positive. All cultured bacteria were isoniazid-sensitive. From our data we drew the following conclusions: isoniazid therapy did not prove successful when inflamed lymph nodes exceeded a certain size. Suppurative lymphadenitis in lymph nodes exceeding 1.0 to 1.5 cm usually led to infiltration or even perforation of the skin. Surgery prevents these complications and significantly reduces healing time. Adjuvant isoniazid therapy cannot be recommended, except for generalized BCG tuberculosis.

Antitubercular Agents↗
PubMed1997

Effect of antiretroviral combination therapy (zidovudine/didanosine or zidovudine/lamivudine) on quantitative plasma human immunodeficiency virus-ribonucleic acid in children and adolescents infected with human immunodeficiency virus.

OBJECTIVE: To assess human immunodeficiency virus (HIV) ribonucleic acid load in children and adolescents with HIV infection who are being treated with antiretroviral combination therapy. STUDY DESIGN: Five patients whose disease progressed with their prior antiretroviral therapy had treatment regimens changed to zidovudine (ZDV)/didanosine (DDI) (group A), and the regimens of six patients were changed to ZDV/lamivudine (3TC) (group B). Patients were followed every 4 to 8 weeks for an average period of 8.6 months. Serial determinations of viral copy numbers and CD4 cells were performed. RESULTS: In group A patients' mean relative changes in CD4 cells showed a 20% increase after 4 months (difference not significant (NS)) and a return to baseline after 8 months; in group B patients' mean relative increases of CD4 cells were 72% (p = 0.046) and 50% (NS), respectively. In group A mean relative viral load increased 21% (0.08 log10, NS) and 71% (0.23(10) log, NS), whereas in group B viral load decreased 22% (0.1 log10, NS) and 74% (0.58 log10, p = 0.03) after 4 and 8 months, respectively. After starting antiretroviral combination therapy in group A, there was a slight trend of a decreasing ratio of viral load per number of CD4 cells, whereas in group B this ratio significantly decreased, indicating a marked suppression of viral turnover with ZDV/3TC treatment. CONCLUSION: In a small cohort of pediatric patients, combination therapy with ZDV/3TC was well tolerated and had a strong and sustained effect on the decrease of viral loads similar to results obtained in adults. In patients with ZDV/DDI therapy the reduction of viral load was less pronounced, but treatment groups A and B were not comparable for statistic evaluation.

AIDS-Related Opportunistic Infections↗
PubMed1997

Fibromuscular dysplasia of the internal carotid artery in a child with alpha-1-antitrypsin deficiency.

Fibromuscular dysplasia (FMD) is a non-inflammatory segmental arteriopathy of unknown origin. Most often the renal arteries are affected, however, also mesenteric, lumbar, vertebral, or carotid arteries may be involved. FMD has frequently been reported as a cause of stroke in adults, but very rarely in children. We report the case of an 11-year-old boy who presented with an ischaemic infarction in the anterior part of the territory of the left middle cerebral artery. Angiography demonstrated a 'string of beads' lesion suggestive of FMD causing occlusion at the origin of the middle artery. Laboratory analyses revealed the protease inhibitor (Pi) phenotype SZ (PiSZ) of alpha-1-antitrypsin deficiency as well as decreased antioxidants and signs of enhanced lipid peroxidation. Such an imbalance may be associated with diminished resistance to oxidation, possibly causing direct cellular and tissue injury. Whether alpha-1-antitrypsin deficiency and an impaired status of antioxidants, as seen in our patient, might play a role in the pathogenesis of FMD is presently unclear.

Antioxidants↗
PubMed1995

Persistent rubella infection after erroneous vaccination in an immunocompromised patient with acute lymphoblastic leukemia in remission.

A 16-year-old male patient with acute lymphoblastic leukemia in complete remission and on maintenance treatment with weekly oral methotrexate and daily oral 6-mercaptopurine for 3 months was immunized in error with the WI-RA 27/3-HDC live attenuated rubella vaccine. Increasing rubella HAI antibodies were noted from 3 to 7 months post-vaccination as well as high levels of IgM antibody up to 8 months in three different tests. High HAI antibody titers persisted for 12-18 months after vaccination. Persisting rubella virus was indicated by PCR detection of rubella-specific nucleic acid in whole blood, non-stimulated and stimulated mononuclear cells 8 months following vaccination. Further attempts to detect rubella virus RNA in two subsequent blood samples were negative. Since acute arthritis and arthralgia occurred in the second month (days 51-63) after vaccination, antileukemic chemotherapy had to be interrupted. Evidence of higher risk for chronic or relapsing rubella-associated arthropathy in immunologically compromised patients and the need to interrupt antileukemic chemotherapy should warrant immunoprophylaxis with polyvalent immune globulin in rubella-susceptible patients who are immunocompromised.

Adolescent↗
PubMed1995

[Cat scratch disease caused by Bartonella henselae].

Bartonella henselae is an etiologic agent of cat-scratch disease and, in immunocompromised patients, of bacillary angiomatosis and other severe syndromes. Cat-scratch disease usually presents as lymphadenopathy, which resolves spontaneously within 2-4 months. The utility of antibiotic therapy remains controversial. In Tyrol four cases of human cat-scratch disease were diagnosed in children in 1994, yielding a prevalence of 0.7/100,000 per year. A 3-year-old boy had lymphadenitis coli since one year despite antituberculosis therapy which was initiated because of the histopathological picture and a positive tuberculin reaction (despite negative mycobacteria-cultures and -PCR). Two girls, age 9 and 13 years, had lymphadenitis at upper or lower extremities after cat-scratches from kittens. A 13-year-old boy presented with febrile illness and right hip pain, computer tomography revealed an osteolytic lesion; symptoms subsided within 3 weeks. Diagnosis of cat-scratch disease is based on cat contact, negative studies for other similar diseases, characteristic histopathologic features (if available), and results of an indirect immunofluorescence test (antigen: Houston-1 isolate, ATCC 49882). We believe that the availability of this serological test will increase the number of diagnosed cases of human Bartonella henselae infections.

Adolescent↗
PubMed1993

Vero cytotoxin-producing Escherichia coli O157 infections in Austria.

To determine the prevalence of Vero cytotoxin-producing Escherichia coli (VTEC) serotype O157 associated diarrhea in the Austrian patient population, we surveyed all stool specimens of liquid consistency submitted to the Federal Public Health Laboratory (FPHL) in Innsbruck for 2 years for this organism. This laboratory serves a population of approximately 1 Million people. Of 5,265 stool specimens, 7 yielded O157 VTEC. Five isolates of E. coli O157 phage type 32, VT2 were cultured from specimens received during a three day period from residents in the county of Schwaz. During the investigation of this "outbreak" E. coli O157 strains were also isolated from two household contacts. Only 1 out of 8 persons with E. coli O157 diarrhea had bloody stools, although 5 of 7 tested specimens (= 71%) also yielded Campylobacter jejuni. None of our patients received antimicrobial therapy directed against E. coli O157 (one child had josamycin). There were no fatalities and no cases of hemolytic uremic syndrome (follow up period: 6 months). Consumption of hamburger, roast beef, and unpasteurized milk was not confirmed in this study. In Austria, no O157 VTEC strain was isolated till June 1992, although at the FPHL in Innsbruck stool specimens of liquid consistency were cultured for this organism since January 1991.

Adult↗
PubMed1990

Production and characterization of a monoclonal antibody against neopterin.

We have produced and characterized the first monoclonal antibody against neopterin (D-erythro-6-(1,2,3,-trihydroxypropyl)pterin). The antibody specifically recognizes neopterin in a modified RIA. The binding capacity in this assay is 34%, the sensitivity limit of inhibition is 0.9 nmol/l. Cross-reactivity exists with monapterin (L-threo(1,2,3,trihydroxypropyl)pterin) in 30%, with other pteridines cross-reactivity has been found in less than 5%.

Animals↗
PubMed1990

Characterization of monoclonal antibodies to human immunodeficiency virus type 1 gp41 by HIV-1 polypeptides expressed in Escherichia coli.

Two monoclonal antibodies (MAbs) were produced in Balb/c mice by immunization with recombinant gp41 derived from expression of lambda-BH10 cDNA of the human immunodeficiency virus-1 (HIV-1) in the prokaryotic expression vector pEX-41. Characterization of the epitopes recognized by these MAbs was done with HIV-1 envelope (env) fusion proteins expressed in Escherichia coli encoding ten distinct segments of the env proteins. In comparison, another mouse MAb, M25, a human MAb directed against gp41, which was produced by the xeno hybridoma line 3D6 and a pool of human patient sera containing antibodies to HIV-1 were tested. We were able to demonstrate that the epitopes recognized by our MAbs are located between arg732 and ser759 of the HIV-1 env glycoprotein gp160 of HTLV-III strain B. M25 reacted with epitopes between ser647 and pro731, which includes the hydrophobic transmembrane region of gp41. The human MAb against gp41, 3D6 reacts with epitopes between ile474 and trp646, a polypeptide stretch consisting of gp120 and gp41 specific amino acids. The human serum pool, positive for HIV-1 antibodies, reacted predominantly with antigenic determinants located between ile474 and leu863. The recombinant env fusion proteins were initially produced to test the immunoreactivity with patient sera and to characterize epitopes which are relevant for immunodiagnostic purposes. In this study, we showed that the set of recombinant env proteins is also a simple and accurate tool for the characterization of MAbs directed to the HIV envelope proteins.

Animals↗
PubMed1989

Anti-viral antibodies in HIV (HTLV-III) infection possess auto-antibody activity against a CH1 domain determinant in human IgG: possible immunological consequences.

Two regions of the envelope glycoprotein gp120 of the human immunodeficiency virus were shown to have a significant degree of homology to human immunoglobulin-gamma heavy-chain constant domains. We have now synthesized three short linear peptides, the first representing a sequence within the CH1 domain, the second an analogue of it, and the third representative of a region within the viral gp120. Polyclonal antibodies against these peptides were raised in rabbits and used to demonstrate that they all reacted well with human native IgG. Vice-versa, we observed the reaction of these antisera to the virus in an ELISA system. The proportion of sera reacting with the human gamma-chain peptide was significantly higher in HIV-positive individuals than in HIV-negative individuals, suggesting production of anti-viral antibodies in AIDS patients with auto-antibody activity against a CH1 domain determinant in human IgG.

Acquired Immunodeficiency Syndrome↗