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Biomedical subjects

A Fischer

Publications and source records attributed to A Fischer.

At least 145 records · Page 8Linked to original sources
PubMed2001

Extracorporeal shock wave therapy of nonunion or delayed osseous union.

One hundred fifteen patients with nonunions or delayed fracture healing were treated with high-energy shock waves. After shock wave treatment, immobilization of the fracture also was done. The followup was at least 3 months and as long as 4 years. In 87 patients (75.7%), one treatment with shock waves resulted in bony consolidation with a simultaneous decrease in symptoms. Besides negligible local reactions (swelling, hematomas, petechial hemorrhages), no complications were observed. The treatment was noninvasive, and personnel and technical requirements were not problematic. The authors concluded that the application of extracorporeal shock wave therapy should be the first choice of treatment for patients with nonunions and delayed bone fracture healing.

Adolescent↗
PubMed2001

Characterisation of Hafnia alvei isolates from human clinical extra-intestinal specimens: haemagglutinins, serum resistance and siderophore synthesis.

Extra-intestinal Hafnia alvei isolates are rarely considered to be pathogenic. To investigate whether such strains are able to produce virulence factors, a total of 70 clinical H. alvei isolates was compared with clinical extra-intestinal isolates of other members of the enterobacterial tribe Klebsiellae (Kiebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens). Whereas mannose-sensitive haemagglutination (MSHA) was less common in H. alvei (59%) than in K. pneumoniae (86%) and E. cloacae (89%) isolates, the incidences of mannose-resistant haemagglutination indicative of type 3 pili (MR/K-HA) and of serum resistance properties were not lower. All H. alvei strains secreted siderophores but, unlike the other enterobacterial species examined, the siderophore type was neither enterobactin nor aerobactin. Although the low pathogenicity of H. alvei isolates could not be attributed to any of the factors investigated, the mean number of factors expressed by each H. alvei isolate was significantly lower than that expressed by K. pneumoniae and E. cloacae isolates but did not differ significantly from that of S. marcescens. Based on these findings, the low pathogenicity of H. alvei appears to be due to its low frequency of expression of virulence factors as compared with clinically significant species such as K. pneumoniae and E. cloacae.

Blood Bactericidal Activity↗
PubMed2001

Symptoms and HPV infection of the vulva: clinical manifestations or mere coincidence?

Two hundred women with abnormal Pap smears and/or vulvar symptoms and 30 with normal Pap smears were investigated to determine the association between symptoms and (i) human papilloma virus infection of the vulva, and (ii) a spongiotic tissue reaction or a spongiotic dermatitis of the vulva. All had vulvar colposcopy and biopsy Human papilloma virus infection was diagnosed by histopathology and in situ hybridisation technique. HPV infection was present in biopsies of 48% of asymptomatic women and 33% with symptoms (p = 0.13) and HPV DNA in 37% of asymptomatic women and 31% with symptoms (p = 0.72). Spongiotic tissue reaction was diagnosed in 53.5% of asymptomatic women compared to 74% of symptomatic women (p = 0.007). This study suggests that vulvar symptoms are not clinical manifestations of HPV infection, but may be caused by dermatitis rather than HPV infection per se.

Adolescent↗
PubMed2001

In vitro development of resistance to six quinolones in Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus.

Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus isolates were exposed to subinhibitory MICs of ciprofloxacin, sparfloxacin, gatifloxacin, moxifloxacin, clinafloxacin, and gemifloxacin during a 10-day period. Subculturing led to resistance development, regardless of the initial potencies of the quinolones. None of the quinolones was associated with a significantly slower rate of resistance development.

Anti-Infective Agents↗
PubMed2001

A novel approach to temporary stenting: degradable cardiovascular stents produced from corrodible metal-results 6-18 months after implantation into New Zealand white rabbits.

OBJECTIVE: To determine whether corrodible materials may be safely used as biodegradable cardiovascular implants. DESIGN: Corrodible iron stents (> 99.8% iron) were produced from pure iron and laser cut with a stent design similar to a commercially available permanent stent (PUVA-AS16). A total of 16 NOR-I stents were implanted into the native descending aorta of 16 New Zealand white rabbits (mean luminal diameter at the implantation site 3.4 mm, balloon diameter to vessel diameter ratio 1.13). RESULTS: No thromboembolic complications and no adverse events occurred during the follow up of 6-18 months. All stents were patent at repeat angiography after 6 (n = 9), 12 (n = 5), and 18 months (n = 2) with no significant neointimal proliferation, no pronounced inflammatory response, and no systemic toxicity. CONCLUSIONS: This initial in vivo experience suggests that degradable iron stents can be safely implanted without significant obstruction of the stented vessel caused by inflammation, neointimal proliferation, or thrombotic events.

Absorbable Implants↗
PubMed2001

Intestinal peptide transport: ex vivo uptake studies and localization of peptide carrier PEPT1.

The nature of protein breakdown products and peptidomimetic drugs such as beta-lactams is crucial for their transmembrane transport across apical enterocyte membranes, which is accomplished by the pH-dependent high-capacity oligopeptide transporter PEPT1. To visualize oligopeptide transporter-mediated uptake of oligopeptides, an ex vivo assay using the fluorophore-conjugated dipeptide derivative D-Ala-Lys-N(epsilon)-7-amino-4-methylcoumarin-3-acetic acid (D-Ala-Lys-AMCA) was established in the murine small intestine and compared with immunohistochemistry for PEPT1 in murine and human small intestine. D-Ala-Lys-AMCA was accumulated by enterocytes throughout all segments of the murine small intestine, with decreasing intensity from the top to the base of the villi. Goblet cells did not show specific uptake. Inhibition studies revealed competitive inhibition by the beta-lactam cefadroxil, the angiotensin-converting enzyme inhibitor captopril, and the dipeptide glycyl-glutamine. Controls were performed using either the inhibitor diethylpyrocarbonate or an incubation temperature of 4 degrees C to exclude unspecific uptake. Immunohistochemistry for PEPT1 localized immunoreactivity to the enterocytes, with the highest intensity at the apical membrane. This is the first study that visualizes dipeptide transport across the mammalian intestine and indicates that uptake assays using D-Ala-Lys-AMCA might be useful for characterizing PEPT1-specific substrates or inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Investigation of the penetration behaviour of mycophenolate mofetil from a semisolid formulation into human skin ex-vivo.

Mycophenolate mofetil, the morpholinoethylester of mycophenolic acid, is an immunosuppressant used in combination with ciclosporin (cyclosporin) and corticosteroids to prevent organ rejection after heart and kidney transplantations. The drug seems also to be effective in dermal diseases after systemic administration. However, up to date mycophenolate mofetil can be only systemically administered and this is associated with several side effects such as nausea, leucopenia, sepsis, and diarrhoea. The aim of this study was to develop a topical formulation containing mycophenolate mofetil and to investigate in-vitro release and penetration into human skin ex-vivo. HPLC was applied to quantify mycophenolate mofetil after release studies from semisolid formulations using a dodecanol-collodion membrane as a lipophilic acceptor. Penetration studies with an amphiphilic cream using excised human breast skin were carried out in Franz-type diffusion cells. Mycophenolate mofetil and its active metabolite mycophenolic acid were detected by HPLC-MS after microsectioning in different skin layers. In this study the penetration of mycophenolate mofetil from an amphiphilic cream into excised human skin was shown. Additionally, the enzymatic hydrolysis of penetrated mycophenolate mofetil into mycophenolic acid was proven even under ex-vivo conditions. In-vivo a higher extent of metabolism of mycophenolate mofetil to mycophenolic acid would be expected because of the complete enzyme activity. This topical formulation might be a promising alternative to the usual systemic administration of mycophenolate mofetil in the treatment of skin diseases such as psoriasis.

Adult↗
PubMed2001

Zinc inhibits the mixed lymphocyte culture.

The mixed lymphocyte culture (MLC) is an established clinical method for bone marrow transplantation, as it serves as an in vitro model for allogenic reaction and transplantation. We previously showed that cytokine release into the supernatant is a more specific and sensitive parameter for cross-reactivity in the MLC than the common measurement of cell proliferation. Therefore we tried to find an inhibitor of the MLC in vitro with the least side effects in vivo, measuring interferon (IFN)-gamma as one of the most important cytokines in posttransplant medicine. Earlier studies showed that zinc is an important trace element for immune function with both stimulatory and inhibitory effects on immune cells. We found that slightly elevated zinc concentrations (three to four times the physiological level), which do not decrease T-cell proliferation in vitro nor produce immunosuppressive effects in vivo, suppress alloreactivity in the mixed lymphocyte culture. In this report we analyzed the mechanism whereby zinc influences the MLC to possibly find a nontoxic way of immunosuppression.

Bone Marrow Transplantation↗
PubMed2001

[T-cell-depleted HLA non-identical bone marrow transplantation in the child: prevention of graft-versus-host reaction by administration of donor T lymphocytes alloreactive against the recipient].

The success of HSCT from HLA partially disparate donors depends on the development of new strategies able to efficiently prevent GVHD and to protect patients from infections and relapse. Using an immunotoxin (IT) directed against the alpha-chain (p55) of the human IL-2r (RFT5-SMPT-dgA), we have previously shown that it is possible to kill mature T cells activated towards a specific HLA complex by a one-way MLR. We designed a clinical trial assessing the effect of infusing increasing doses of T lymphocytes in the setting of children recipients of non HLA genetically identical HSCT. Thirteen patients have been enrolled from September 1998 to April 2000 and fourteen HSCT have been realized in 13 patients (pts). Donors were MUD in 3 cases and familial HLA partially disparate in the remaining cases. Allodepleted donor T cells were injected between day +14 and day +30 provided that ATG was undetectable in the serum and blood PMN counts was > 500/microliter. The mean age of these patients was 17 months (range 1 to 42). Diagnosis included immune deficient and malignant hemopathies. Three patients received 1 x 10(5) allodepleted T cell/kg, 7 patients received 4 x 10(5)/kg and 4 patients received 6 x 10(5)/kg allodepleted T cells. Full inhibition of MLR was achieved in 12 out of 14 cases. In two cases, a residual T cell reactivity to the recipient was observed (4 to 5%) and patients developed grade II aGVHD. aGVHD occurred in 4 out of 11 grafted patients (all grade II). No chronic GVHD has developed, so far. Three patients died from severe VOD or PHT at day +34, day 51 and day +166, while one infected patient by VZV, CMV and EBV before HSCT died 6 months after transplantation from meningoencephalitis and another patient died from relapse at day +291. The patient for which there was no engraftment died at day +48 from staphylococcus infection. Overall survival is 54%, with a median follow up of 8 months; the mean time to reach a blood lymphocyte count > 500 was 41 days, to reach a CD3 count > 300 microliters 63 days (20-111), CD4 > 200 microliters 97 days and positive mitogen-induced proliferation 90 days. In three patients, a tetanus-toxoid positive proliferation was detected before immunization. From this intermediate analysis, we conclude that 1) specific allodepletion is an effective approach to prevent aGVHD in a haploincompatible setting, 2) data on immunological reconstitution suggest that infused T cells do survive and expand. A higher number of patients must be enrolled to determine the optimal number of T cells to infuse.

Acute Disease↗
PubMed2001

Gene therapy: some results, many problems to solve.

Gene therapy is raising incredible hopes. The prospects of treating numbers of severe pathologies (hereditary, cancerous, degenerative or infectious) are vast. Nevertheless, the technological bolts to lift are still numerous, whether they be bringing the vectors into focus, the systems of expression of transgenes or the neutralization of immune responses of the host against the vector, the product of transgenes, or the knowledge of the considered pathologies of physiopathology. Solving these difficulties entails the gathering of multiple disciplines, from chemistry to medicine, passing through virology and immunology.

Adenoviridae↗
PubMed2000

Fischer replies:

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Journal Article↗
PubMed2000

Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through multiple interacting bHLH factors.

Vertebrate somitogenesis comprises the generation of a temporal periodicity, the establishment of anteroposterior compartment identity, and the translation of the temporal periodicity into the metameric pattern of somites. Molecular players at each of these steps are beginning to be identified. Especially, members of the Notch signaling cascade appear to be involved in setting up the somitogenesis clock and subsequent events. We had previously demonstrated specific expression of the mHey1 and mHey2 basic helix-loop-helix (bHLH) factors during somitogenesis. Here we show that perturbed Notch signaling in Dll1 and Notch1 knockout mutants affects this expression in the presomitic mesoderm (PSM) and the somites. In the caudal PSM, however, mHey2 expression is maintained and thus is likely to be independent of Notch signaling. Furthermore, we analysed the dynamic expression of the respective chicken c-Hey1 and c-Hey2 genes during somitogenesis. Not only is c-Hey2 rhythmically expressed across the chicken presomitic mesoderm like c-hairy1, but its transcription is similarly independent of de novo protein synthesis. In contrast, the dynamic expression of c-Hey1 is restricted to the anterior segmental plate. Both c-Hey genes are coexpressed with c-hairy1 in the posterior somite half. Further in vitro and in vivo interaction assays demonstrated direct homo- and heterodimerisation between these hairy-related bHLH proteins, suggesting a combinatorial action in both the generation of a temporal periodicity and the anterior-posterior somite compartmentalisation.

Amino Acid Sequence↗