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Biomedical subjects

D Hofmann

Publications and source records attributed to D Hofmann.

At least 55 records · Page 3Linked to original sources

[Differential cytology of bronchoalveolar lavage fluid in healthy children in comparison with children colonized by lung-specific pathogens].

BAL is increasingly used in the assessment of pulmonary diseases, however, the role in children remains to be defined. Therefore bronchoalveolar lavage (BAL) was performed on 21 healthy children in order to enable quantification and characterization of the alveolar cell populations. Reference values for cellular constituents of BAL fluid using rigid bronchoscopes are lacking-even though in children still 90% of bronchoscopies are done by rigid instruments and BAL is performed using a catheter leading into the lower lobe. The children, 12 months to 14 years of age, were lavaged adjusted to body weight with three 1 ml/kg aliquots of normal saline. Recovery was 31 +/- 12%. Each aliquot was analysed separately. The number of total cell count per milliliter was 29.8 x 10(4) (range 0.6-161 x 10(4). Percentages of different cell types of the third simple were (mean): macrophages 88.5, lymphocytes 6.4, neutrophils 4.8, eosinophils 0.1, basophils 0%. Significantly more neutrophils and less lymphocytes were found in the first as compared to the second and third sample. No age dependency was observed for either cell type. The comparison to cellularity of BAL-fluid with proven evidence of Adenovirus, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae type B showed a marked influence of viral and bacterial germs. The study provides the first reference data on BAL differential cytology in healthy children using rigid bronchoscopy.

Adolescent↗

[Bronchial asthma in childhood].

Bronchial asthma in childhood is defined as a disease presenting with wheezing, dyspnea and cough on the basis of an inflammatory bronchial hyperreagibility. It is the most common chronic disease in childhood. There are a variety of causes for asthma. Certainly allergy is the most common cause in childhood but also environmental pollution is of importance. Asthmatic attacks, episodes of asthma and asthmatic cough are the most frequent clinical manifestations where as the malignant, hypoxemic asthma crisis is of special importance since its mortality is as high as 0.5-0.8/100,000. Special notice has to be taken on the evaluation of obstructive bronchitis in infancy and childhood which might be very difficult. During the past years, the use of inhalative steroids in the long term treatment has gained increasing importance also in childhood, since it could be demonstrated that side effects of clinical relevance are hardly to be expected.

Adrenergic beta-Agonists↗

Reduced glutathione and S-acetylglutathione as selective apoptosis-inducing agents in cancer therapy.

The effect of reduced glutathione (GSH) and S-acetylglutathione (S-acglu) treatment on several tumor cell lines and normal cells in vitro was investigated. GSH and S-acglu applied at concentrations of 1 mM and 2 mM induced apoptosis in malignant cells as shown by DNA-fragmentation and staining of apoptotic cells with 7-amino-actinomycin D while viability and growth of normal cells were not significantly influenced by this treatment. The results demonstrated that GSH and S-acglu may be selective inducers of apoptosis in malignant cells.

Apoptosis↗

Simple determination of polysaccharide specific antibodies by means of chemically modified ELISA plates.

A new ELISA technique using Nunc CovaLink NH microtiter plates has been developed to measure anticapsular polysaccharide specific antibodies. Capsular polysaccharide (PS) of Haemophilus influenzae type b (PRP) and pneumococcal antigens types 3, 6, 8, 14, 19, 23 were immobilized on CovaLink NH. These are modified plates with secondary amino groups bound to their surface which, in the presence of a water-soluble carbodiimide as coupling reagent, facilitate the direct binding of polysaccharides. We compared the binding characteristics of PS antigens to CovaLink NH and a conventional polystyrene ELISA plate. Checkerboard titration of PS antigens between 0.04-30 micrograms/ml clearly demonstrated that with Covalink NH optimal binding of a pooled serum from immunized donors was achieved for all PS antigens tested at a concentration of 1 microgram/ml, while binding of PS to the conventional plate was rather poor even at concentrations of 30 micrograms/ml. The CVs for the ELISA ranged from 1.1 to 2.8% for intra-assay comparisons and from 3.6 to 7.3% for inter-assay comparisons. In addition, when PRP-IgG antibodies were determined with the CovaLink NH ELISA and compared with the Farr assay an acceptable correlation ( r = 0.89, p < 0.0001) was obtained. The technique described provides a simple and sensitive tool for evaluating specific immunity to PS antigens.

Antibodies, Bacterial↗

Nuclear magnetic resonance imaging of airways in humans with use of hyperpolarized 3He.

The nuclear spin polarization of noble gases can be enhanced strongly by laser optical pumping followed by electron-nuclear polarization transfer. Direct optical pumping of metastable 3He atoms has been shown to produce enormous polarization on the order of 0.4-0.6. This is about 10(5) times larger than the polarization of water protons at thermal equilibrium used in conventional MRI. We demonstrate that hyperpolarized 3He gas can be applied to nuclear magnetic resonance imaging of organs with air-filled spaces in humans. In vivo 3He MR experiments were performed in a whole-body MR scanner with a superconducting magnet ramped down to 0.8 T. Anatomical details of the upper respiratory tract and of the lungs of a volunteer were visualized with the FLASH technique demonstrating the potential of the method for fast imaging of airways in the human body and for pulmonary ventilation studies.

Adult↗

Trisomy of human chromosome 18: molecular studies on parental origin and cell stage of nondisjunction.

We investigated the parent and cell division of origin of the extra chromosome 18 in 62 aneuploids with a free trisomy 18 by using chromosome-18-specific pericentromeric short-sequence repeats. In 46 cases, DNA of patients was recovered from archival specimens, such as paraffin-embedded tissues and fixed chromosomal spreads. In 56 families, the supernumerary chromosome was maternal in origin; in six families, it was paternal. Among the 56 maternally derived aneuploids, we could exclude a postzygotic mitotic error in 52 cases. Among those in which the nondisjunction was attributable to an error at meiosis, 11 were the result of a meiosis I nondisjunction and 17 were caused by a meiosis II error. This result differs markedly from findings in acrocentric chromosomes where nondisjunction at maternal meiosis I predominates. Among the six paternally derived cases, two originated from a meiotic error, indicating that a nondisjunction in paternal meiosis is not as rare as previously suggested.

Adult↗

Normal and abnormal pulmonary ventilation: visualization at hyperpolarized He-3 MR imaging.

To assess the feasibility of helium-3 magnetic resonance (MR) imaging with a three-dimensional fast low-angle shot (FLASH) sequence, He-3 gas (volume, 300 mL; pressure, 3 x 10(5) Pa; polarized up to 45% by means of optimal pumping) was inhaled by five healthy volunteers and five patients with pulmonary diseases. All breath-hold examinations (22-42 seconds) were completed successfully. Normal ventilation was depicted with homogeneous high signal intensity, lesions were depicted as causing defects, and obstructive lung disease was depicted with severely inhomogeneous signal intensity.

Administration, Inhalation↗

Gene-targeted inhibition of transactivation of human immunodeficiency virus type-1 (HIV-1)-LTR by antisense oligonucleotides.

We have used an in vitro approach to study the efficiency of antisense oligonucleotides in inhibiting LTR-(HIV-1)-directed CAT expression catalyzed by tat protein, the functional protein of the transactivator gene. We selected the target sequence localized near the 5' end of the tat mRNA. The following conclusions can be drawn from the data presented here: a) Antisense oligonucleotides modified by conjugation of cholesterol at the 3' end have a severalfold higher inhibitory response, b) inhibitory response is dependent on the mode of introducing oligonucleotides, and c) the inhibition by antisense oligonucleotides is sequence specific and directed towards the targeted region. This approach could be useful for targeting functional regions of regulatory gene products and designing gene-targeted inhibitors of virus replication.

Animals↗

Improved global and regional left ventricular function after angioplasty for chronic coronary occlusion.

Percutaneous transluminal coronary angioplasty can be performed safely and effectively in patients with chronic total coronary occlusion. To investigate the effect on left ventricular function, global and regional left ventricular ejection fraction were analyzed by contrast angiography in 49 patients before and 10 +/- 6 weeks after successful recanalization. Coronary angiography at follow-up showed reocclusion in 12 patients (24%). In 37 patients with patent arteries global ejection fraction increased from 55.8 +/- 7.1% at baseline to 62.5 +/- 11.3% at follow-up (P < 0.001), and regional wall motion assessed by the centerline method improved from -1.7 +/- 1.0 to -0.6 +/- 1.5 standard deviations/chord (P < 0.001). In contrast, in patients with reocclusion neither global ejection fraction nor regional wall motion were significantly different at follow-up compared with baseline. Changes in global or regional left ventricular function after coronary recanalization were unrelated to other parameters such as severity of angina, duration of occlusion, history of myocardial infarction, presence or absence of visible collaterals, or baseline left ventricular function. Thus in patients with primarily successful recanalization of chronically occluded coronary arteries persistent vessel patency is the major determinant of global and regional improvement of left ventricular function.

Adult↗

[Reconstitution of immunoglobulin production in patients with variable immunodeficiency syndrome (CVI) by the CD40 system and IL-10].

Common variable immunodeficiency (CVI) is widely believed to involve a primary B cell defect, however, there is increasing evidence of T cell dysfunction in these patients. To test the hypothesis that B cells of patients with CVI are not defective, we investigated whether immunoglobulin production can be induced by activation through the CD40 system. Our results show that 6 of 7 children with CVI produced IgG when B cells were activated through CD40 plus IL-10. In most patients, IgM and IgA production were also induced. However, we could demonstrate that failure of immunoglobulin production was not due to a defective CD40 ligand expression on T cells. Taken together, our data show that B cells of patients with CVI are functionally normal when activated through CD40 plus IL-10. IL-10 seems to be more effective than IL-2 in restoration of immunoglobulin production in such patients.

Adolescent↗

[Hyper-IgE syndrome--two case reports of unusual complications].

The hyper-IgE syndrome (HIS) is a complex immunologic disease, caused by an unknown basic defect. We report on two cases showing complications, which have not been described so far. Case 1: A 15-year-old boy suffering from HIS developed a liver tumour with severe eosinophilic infiltration and degranulation. The transformation process of the liver histologically resembled focal nodular hyperplasia. Therapy with cyclosporine A did not lead to clinical benefit. Now, a therapeutic attempt with interferon gamma is made. Case 2: In a 17-year-old female HIS patient, multiple papillomas and ulcers of the mucous membrane, caused by infection with human papilloma virus, emerged in the ENT region. Under treatment with interferon alpha, papillomatosis could be restrained. As therapy of the hyper-IgE syndrome only symptomatic treatment has been recommended so far. Future therapies should strive for systemic immunomodulation by application of cytokines or soluble cytokine receptors like interferons or sIL-4R.

Adolescent↗

Evidence for sustained platelet activation in patients with early postinfarction angina.

Excretion of 2,3-dinor-thromboxane B2 released from activated platelets has been found elevated in patients with acute myocardial infarction and unstable angina. To investigate the role of thrombotic activity in postinfarction angina we measured urinary concentrations of 2,3-dinorthromboxane B2 in 20 patients over 10 days after myocardial infarction. Compared with 11 patients recovering pain-free, excretion of 2,3-dinorthromboxane B2 was found elevated in 9 patients who developed postinfarction angina. Accordingly, early postinfarction angina appears to be associated with ongoing thrombotic activity.

Aged↗

Retrospective study of the parental origin of the extra chromosome in trisomy 18 (Edwards syndrome).

The parental origin of the extra chromosome in trisomy 18 was traced in 30 informative families using highly polymorphic (CA) repeats mapped on the long arm of chromosome 18. Proband DNA was recovered from slides of chromosome preparations in 28 cases and from paraffin-embedded tissues in two cases. The extra chromosome was found to be of maternal origin in 26 cases (86.7%), and paternal origin in 4 cases (13.3%).

Adult↗

Combined therapy in human immunodeficiency virus-infected children--a 4-year experience.

From 1988 to 1991 the long-term efficacy of a combined therapy with a polyvalent immunoglobulin/cytomegalovirus (CMV) hyperimmunoglobulin, oral low dose zidovudine, oral cotrimoxazole or inhaled pentamidine was investigated in three groups of human immunodeficiency virus (HIV)-infected children. Group 1A consisted of three perinatally infected children with a CD4 cell decrease of > 400 cells/microliters per year. Group 1B were 17 perinatally infected children with a CD4 cell decrease of < 400 cells/microliters per year. Group 2 comprised eight haemophilic children infected by clotting factors. Despite combined therapy none of group 1A survived longer than 12 months showing a rapid loss of CD4 cell counts, progressive encephalopathy, wasting syndrome and severe bacterial, fungal and CMV reactivation. Under pure intravenous immunoglobulin (IVIG) therapy severe bacterial infections were seen in 1 of 12 children in group 1B. The majority of these patients showed increases or stabilisation of length and weight percentiles. In this group low dose zidovudine therapy was of benefit in HIV-associated neurological symptoms. Nevertheless combined therapy could not prevent further deterioration of CD4 cell counts. In group 2 severe bacterial infections were not seen under IVIG therapy. In this group a temporary increase (6 months) of CD4 cell counts under IVIG/zidovudine combined therapy occurred. Pneumocystis carinii pneumonia (PCP) prophylaxis with oral cotrimoxazole or inhaled pentamidine successfully prevented PCP in all three groups. Under CMV hyperimmunoglobulin (n = 22), ten out of ten patients did not acquire primary CMV infection, whereas CMV reactivations mainly located in the CNS could not be prevented in 5 of 12 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-Positive T-Lymphocytes↗