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Biomedical subjects

A Fischer

Publications and source records attributed to A Fischer.

At least 397 records · Page 22Linked to original sources
PubMed1996

Inhibition by zinc protoporphyrin-IX of vasoactive intestinal peptide-induced relaxations of guinea pig isolated trachea.

Carbon monoxide, formed as a product of heme oxygenase activity, has been postulated to act as an intra- and intercellular messenger molecule. We addressed the hypothesis that heme oxygenase is involved in the relaxation of the guinea pig trachealis elicited by vasoactive intestinal peptide (VIP) or by electrical field stimulation. Immunohistochemical studies revealed the presence of heme oxygenase-II in airway smooth muscle and epithelium. Zinc protoporphyrin-IX (ZnPPn), an inhibitor of heme oxygenase, effectively inhibited VIP-induced relaxations of tracheal smooth muscle. Surprisingly, the potency of ZnPPn was increased if the drug was preincubated with the VIP solution before addition to the tissue bath. The relaxant responses to 3-morpholinosydnonimine were unaffected by ZnPPn. Zinc deuteroporphyrin-IX 2,4 bisglycol, a more potent inhibitor of heme oxygenase than ZnPPn, did not affect the VIP responses. ZnPPn (300 microM) had no effect on nonadrenergic, noncholinergic relaxations of the guinea pig trachea. These data indicate that although ZnPPn is an efficacous inhibitor of VIP-induced relaxations of the guinea pig trachealis, it is unlikely that heme oxygenase plays an important role in this response. Rather, the data are consistent with the hypothesis that ZnPPn inhibits the VIP response via an interaction with the VIP molecules themselves. Although the results demonstrate the existence of heme oxygenase-II in the guinea pig trachealis, they do not support the hypothesis that it plays a role in electrical field stimulation-induced nonadrenergic, noncholinergic relaxations.

Animals↗
PubMed1996

Bone marrow transplantation from genetically HLA-nonidentical donors in children with fatal inherited disorders excluding severe combined immunodeficiencies: use of two monoclonal antibodies to prevent graft rejection.

OBJECTIVE: For children with life-threatening inborn errors of metabolism without a matched related bone marrow donor, transplantation from an HLA genetically nonidentical donor is the only therapeutic option. To reduce the high risk of graft rejection in this setting without increasing the conditioning regimen, a protocol based on the infusion of an antiadhesion antibody directed against the CD11a (leukocyte function-associated antigen 1 [LFA-1]) molecule was performed by the European Bone Marrow Transplantation-European Society for Immunodeficiency group with promising results. To optimize engraftment, and thereby survival, further, the additional blockade of a second important leukocyte adhesion and signalization pathway mediated by the CD2 and LFA-3 interaction was attempted in a multicenter protocol conducted by the European Bone Marrow Transplantation-European Society for Immunodeficiency group. Results of this study (ie, engraftment and survival) were compared with a historical control group that received the anti-LFA-1 antibody alone. Factors that may have affected engraftment and survival were also considered in this study. METHODS: Forty-four children with inborn errors, including inherited immunodeficiencies (excluding severe combined immunodeficiencies), Chédiak-Higashi syndrome, familial hemophagocytic lymphohistiocytosis, and malignant osteopetrosis, received bone marrow from HLA-nonidentical related donors or from HLA-identical unrelated donors at 13 European centers between August 1990 and June 1993. Bone marrow was depleted of T cells by use of either erythrocyte (E) rosetting or monoclonal antibodies (MoAbs) to prevent graft-versus-host disease. The conditioning regimen consisted of busulfan and cyclophosphamide for all patients plus etoposide for patients with osteopetrosis, familial hemophagocytic lymphohistiocytosis, and Chédiak-Higashi syndrome. Infusions of MoAbs specific for the CD11a and the CD2 molecules were started 4 and 3 days, respectively, before and continued through the first 10 and 11 days, respectively, after bone marrow transplantation (a total of 14 injections). RESULTS: The overall sustained engraftment rate was 69.8%, with full chimerism in 80.6% of patients and no late graft rejection with the use of two MoAbs versus 65.7% and 58.1%, respectively, in the control group, in which only one MoAb was infused. The overall actuarial survival rate with a functional graft was 40.9%, with a mean follow-up of 39.3 months with two MoAbs versus 37.8% with one. The engraftment rate was significantly influenced by the T-cell depletion method, with better results for recipients of E rosette- depleted marrow (78.6% vs 20% for Campath 1-M plus complement-depleted marrows). Graft-versus-host disease and the kinetics of immune reconstitution were similar in both groups. CONCLUSIONS: The overall engraftment rate and overall survival rate with engraftment in patients treated with anti-LFA-1 and anti-CD2 were similar to those in patients treated with anti-LFA-1 antibody alone. However, although the number of patients is too small to draw definitive conclusions, results from the combined use of the two MoAbs indicates a trend toward better engraftment and survival after infusion of E rosette-depleted marrow. Further improvement in survival would demand additional strategies to hasten immunologic recovery.

Antibodies, Monoclonal↗
PubMed1996

[Effect of resorption of Purisole (mannitol/sorbitol solution) as a distention medium in hysteroscopic operations on cardiovascular and laboratory parameters and energy metabolism--a prospective non-randomized observational study].

This paper reports on an open explorative study on the absorption of the electrolytfree distension medium Purisole (Mannitol-Sorbitol solution) during hysteroscopic procedures and its effects on laboratory and cardiovascular parameters. Intra- and postoperative levels of mannitol and sorbitol in urine were also measured to determine elimination of both components. The study population consisted of 84 patients aged 22-62 years. 54 women underwent ablative (resection of submucous fibroids, endometrial ablation, septum resection), 30 patients non-ablative operative hysteroscopic procedures (synechiolysis, hysteroscopic proximal tubal catheterisation). The duration of operations was between 23-48 minutes. Ethanol was added to the Purisole solution for determination of resorption. In 57 cases 1% ethanol in Purisole was used as irrigating fluid. In 27 cases 2% ethanol was added to the distension fluid. A median slight encrease of central venous pressure was noted during the procedures. 18 women had an intraoperative hyponatriaemia (only 4 patients < 130 mmmol/1). For the 15 patients, in which ethanol absorption was noted, fluid resorption was calculated on the basis of blood alcohol concentration (median 850 ml). Resorption was below the determination threshold in the other 69 women. Urine examination showed intra- and postoperatively increased concentrations of sorbitol and mannitol. Fluid overload and intraoperative cardiovascular complications did not occur in our patients.

Adult↗
PubMed1996

Bone marrow gene transfer in three patients with adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency results in severe combined immune deficiency disease (SCID), which is fatal without treatment. Allogeneic bone marrow transplantation (BMT) is the treatment of choice if an HLA-identical sibling bone marrow donor is available, resulting in almost 100% cure rate. BMT-related mortality is high in patients lacking such a donor. For these patients, efficient transfer of a recombinant ADA gene into hematopoietic stem cells is a therapeutic option if it results in the outgrowth of a 'genetically repaired' lymphoid system. Based on successful gene transfer studies in monkeys, we performed retrovirus-mediated gene transfer into CD34+ bone marrow cells of three patients with ADA deficiency. Two patients received bovine ADA conjugated to polyethylene glycol (PEG-ADA); in the third patient, PEG-ADA was started 4 months after gene transfer. Gene transfer resulted in a 5-12% transduction frequency of in vitro colony forming cells (CFU-Cs). No toxicity was observed during and after infusion of the graft. Following infusion of the transduced CD34+ cells, transduced granulocytes and mononuclear cells persisted in the circulation for 3 months. In addition, the gene was present in the marrow of one of the patients at 6 months after gene transfer. Expression of the gene was not detected. After this period, the gene could not be detected. In monkey studies we showed that myeloablation, which was not performed in the patients, may enhance engraftment of genetically modified cells. We hypothesize that lack of myeloablation, administration of bovine ADA and low numbers of transduced progenitor cells all may have contributed to the relative low numbers of transduced cells in the patients. Under these conditions, no selective advantage of the genetically corrected progenitor cells was observed.

Adenosine Deaminase↗
PubMed1996

[Gene therapy for hereditary immunodeficiencies].

There are numerous inherited immunodeficiencies characterized by either defects in T, B lymphocytes, phagocytic cells or the complement system. About 20 genes involved in inherited immunodeficiencies have now been identified. This opens theorically the possibility to consider gene therapy for the most severe of the diseases. A logical approach consists in attempting gene transfer into hematopoietic stem cells in order to achieve a definitive cure. However, the presently available vectors, i.e. retroviruses induce only stable gene integration and possibly expression into cycling cells while most stem cells are in G0/G1. This precludes at this time efficient gene therapy for many inherited immunodeficiencies. Nevertheless in instances, where there is an early block in cell differentiation like in adenosine desaminase deficiency (ADA) or X-L severe combined immunodeficiency (IL2 R gamma deficiencies), a selective advantage could be provided to the few transduced stem cells enabling progressive lymphocyte differentiation. This hypothesis sets the basis for the ongoing clinical studies in patients with ADA deficiency and will be assessed in available animal model of XL SCID.

Adenosine Deaminase↗
PubMed1996

Idiopathic disseminated bacillus Calmette-Guérin infection: a French national retrospective study.

OBJECTIVE: Disseminated bacillus Calmette-Guérin (BCG) infection after inoculation of live vaccine is considered to result from impaired immunity of the child. However, in half of the cases, regarded as idiopathic, no well-defined immunodeficiency condition can account for the infection. The objective of the present study is to report the prevalence, clinical features, associated infections, and outcomes of children with idiopathic disseminated BCG infection. DESIGN: National retrospective survey during the period from 1974 through 1994 in France. SETTING: All neonatology and pediatrics units in primary care and referral centers throughout France. PATIENTS: Data were collected from 595 (82%) of 721 units, 377 (93%) of 407 centers, and 320 (93%) of 345 cities. Selection criteria included BCG infection, dissemination to at least two areas beyond the inoculation site, and no well-defined immunodeficiency condition. Sixteen children (8 girls and 8 boys), born to families unrelated to each other but often consanguinous (5 of 16) or abroad (5 of 16). RESULTS: The minimal prevalence rate was estimated at 0.59 cases per 1 million vaccinated children born in France. Clinical features included fever and cachexia, disseminated BCG infection to lymph nodes (15 of 16), skin (13 of 16), soft tissues (11 of 16), lungs (11 of 16), spleen (11 of 16), liver (11 of 16), and bones (9 of 16). Eight children had associated or subsequent severe opportunistic infection (50%), with either nontyphi Salmonella enterica serotypes (7 of 16) or Mycobacterium abscessus (1 of 16). The outcome was poor: 8 children (50%) died; the cause of death was BCG infection for most children (7 of 8); 8 survived until the last follow-up (50%). CONCLUSIONS: Idiopathic disseminated BCG infection is a rare but severe complication of BCG vaccination. The infection probably results from an as yet unknown genetically determined immunodeficiency condition that affects the killing of intracellular bacteria such as BCG and Salmonella.

BCG Vaccine↗
PubMed1996

[Sonographic demonstration of an aortic thrombosis in the dog].

A case of aortic thrombosis in a Golden Retriever is reported. The main clinical signs were paresis of the left hind limb, weak femoralis pulses and cool distal limbs. The diagnosis was made by ultrasonography. An echogenic, intraluminal mass was detected in the iliac bifurcation.

Animals↗
PubMed1996

Doppler echocardiographic assessment of the new ATS medical prosthetic valve in the aortic position.

Advancing The Standard (ATS) Medical (ATS Medical Inc., Minneapolis, MN) is a new mechanical bileaflet valve, composed of pyrolitic carbon. The aim of this study was to define in a blinded manner the Doppler echocardiographic characteristics of normally functioning ATS Medical prostheses with respect to their size. Forty consecutive patients (29 men, mean age 58 +/- 13 years), clinically stable, and without evidence of valve dysfunction, were studied from 1993 to 1995. Doppler echocardiography was performed at least 3 months after valve replacement with ATS Medical valves (5 n degrees 21, 8 n degrees 23, 12 n degrees 25, 10 n degrees 27, 5 n degrees 29). Maximum and mean transprosthetic pressure gradients were calculated by the simplified Bernoulli equation. Functional valve surface area was assessed by the continuity equation using the external diameter of the prostheses to calculate the subaortic surface area. The Doppler velocity index was obtained by the ratio of subaortic and transaortic velocities and the performance index was calculated dividing the effective orifice area by the actual orifice area. For the most commonly used aortic valve (25 mm), the maximum pressure gradient was 17 +/- 8 mmHg, the mean gradient 11 +/- 4 mmHg, the functional surface area 2.2 +/- 0.4 cm2, the Doppler velocity index 0.44 +/- 0.07, and the performance index 0.68 +/- 0.11. This study provides the normal range for Doppler hemodynamic characteristics of the various sizes of the ATS valve.

Adult↗
PubMed1995

[Cardiac surgery in octogenarians].

37 patients aged 80 or over underwent cardiac surgery during an 11-year period. Operative indications included angina, dyspnea and syncope. The majority of patients (n = 32) had a left ventricular ejection fraction greater than 0.5. There were 28 aortic valve procedures, of which seven were combined with coronary artery bypass grafts (CABG), and 2 with mitral valve repair; in addition, 7 isolated CABG procedures and one isolated mitral valve repair were performed. 36-day mortality was 5.4% (2 patients); 9 patients died at a later date (2.5 to 118 months after surgery). The most frequent postoperative complications were atrial fibrillation, pulmonary infection or atelectasis, transient delirium and atrioventricular conduction disturbances. Mean hospital stay was 14.5 days. 1- and 5-year actuarial survival rates were 83% and 57%. In a control group of patients aged 60-69 matched for preoperative characteristics, there were no in-hospital fatalities and 1- and 5-year survival were, respectively, 100% and 82%. Among complications, only conduction disturbances and transient delirium were significantly more frequent in the octogenarian group. At follow-up, the proportion of severely symptomatic octogenarians had diminished to 24% from 84%. In conclusion, cardiac surgery can be performed on octagenarians with adequate myocardial reserve, exposing them to a perioperative mortality that is in the range of younger age groups while offering an equivalent prospect for functional improvement.

Age Factors↗
PubMed1995

Allelotype of pancreatic adenocarcinoma using xenograft enrichment.

p53 and MTS1 are known to be mutationally inactivated in pancreatic adenocarcinoma. Other tumor suppressor genes are likely also to play a role. To define chromosomal arms which may harbor additional tumor suppressor genes, we performed an extensive allelotype on pancreatic cancer utilizing a xenograft enrichment technique. Eighty-eight percent (28/32) of primary tumors gave rise to xenografts. Eighteen cases were used in a PCR-based allelotype using 283 polymorphic markers, over 2800 informative assays, and an average coverage of 4.1 informative markers per chromosomal arm per case. Highly frequent allelic loss (> 60%) was seen at chromosomes 1p, 9p, 17p, and 18q. Moderately frequent allelic loss (40-60%) was seen at 3p, 6p, 6q, 8p, 10q, 12q, 13q, 18p, 21q, and 22q. The average fractional allelic loss was 0.36. Allelic and sequence stability was demonstrated among 64 parallel and second-passage xenografts derived from 12 cases of pancreatic adenocarcinoma with the ascertainment of over 3000 single alleles. The findings were confirmed in primary tumors. In only two instances were discrepancies revealed between the allelic loss data obtained from corresponding parallel xenografts, probably due to the xenografting of minor subpopulations, reflecting genetic heterogeneity of the primary tumor.

Adenocarcinoma↗
PubMed1995

Results of allogeneic bone marrow transplantation in patients with leukocyte adhesion deficiency.

We have retrospectively analyzed the outcome of bone marrow transplantation (BMT) in 14 patients with leukocyte adhesion deficiency (LAD) performed in two centers between 1981 and 1993. Five patients received BMT from HLA-identical donors. Nine received T-depleted marrow from two HLA antigen- or haplotype-incompatible parents. Conditioning regimen consisted of chemotherapy exclusively in 13 patients and associated with total body irradiation (TBI) in one patient. In five cases, failure of engraftment occurred as a result of either insufficient myeloablation (n = 3) or, possibly, graft rejection in two cases of moderate phenotype of LAD. The second conditioning regimen consisted of TBI and chemotherapy with the use of anti-lymphocyte function-associated antigen 1 (LFA-1) and anti-CD2 monoclonal antibodies for patients with the moderate phenotype of LAD. These patients were successfully retransplanted. Eight patients developed acute graft-versus-host disease (GVHD). Chronic GVHD occurred in five cases. GVHD led to the death of three patients. Ten patients are alive and well 12 months to 12 years after BMT. Chimerism is full in six of these patients and mixed but stable in four with variable proportion of donor leukocytes. One patient with less than 15% donor leukocytes has mild gingivitis, while the others are well. Sequelae from BMT are limited in two cases to growth retardation caused by TBI. Success of BMT in cases of LAD including seven of nine recipients of HLA nonidentical marrow indicates that this procedure can be proposed as a curative approach to LAD regardless of an available HLA-identical donor. Great care should be taken in GVHD prophylaxis and treatment.

Adolescent↗