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Biomedical subjects

P Zabel

Publications and source records attributed to P Zabel.

At least 19 recordsLinked to original sources
PubMed2006

Disseminated mycobacterium bovis infection in an immunocompetent host.

We report about a rare case of disseminated Mycobacterium bovis infection in a 61 year old female immunocompetent patient with involvement of the lung, the brain, the spleen and spine. The patient had intracerebral tuberculomas with paradoxical enlargement during the first weeks of therapy. We reviewed the data of our microbiological department and found five other patients with Mycobacterium bovis infection diagnosed between 1999 and 2004, which are 5.8 % of all diagnoses of tuberculosis during this period.

Aged↗
PubMed2006

[Pharmacotherapy of severe acute respiratory syndrome (SARS)].

Severe acute respiratory syndrome (SARS) constitutes the first new infectious disease of the current millennium. It is caused by the novel SARS-Coronavirus (SARS-CoV). SARS is related to a high morbidity and mortality and first appeared during an epidemic in 2002 - 2003. To date no specific therapy against the SARS-CoV is available. Due to the rapid spread of SARS during the epidemics in 2002 - 2003, randomised and controlled multicentre studies were not performed. Therefore, general guidelines have not been developed. Since the outbreak, scientists have been testing potential antiviral substances using in vitro and animal models. This study analyses the presently available in vitro and in vivo data on the pharmacotherapy of SARS.

Antiviral Agents↗
PubMed2005

Neutrophil apoptosis, activation and anti-inflammatory cytokine response in granulocyte colony-stimulating factor-treated patients with community-acquired pneumonia.

BACKGROUND: Despite antibiotic treatment, the mortality of severe community-acquired pneumonia (CAP), especially in patients with severe comorbidity, remains high. Innate defense mechanisms including polymorphonuclear neutrophil (PMN) activation and survival, orchestrated by cytokines, are primarily responsible for the elimination of bacterial organisms from the alveolus. OBJECTIVES: The aim of this study was to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on PMN activation, apoptosis and cytokine response in patients with CAP. METHODS: Patients received a single dose of G-CSF (1 x 300 or 480 microg s.c.) prior to standard antibiotic treatment (n=8) or standard treatment only (n=8). Apoptosis rate and expression of CD11b, CD66b, CD64 and CD114 surface molecules on systemic PMN were assessed using fluorescence-activated cell sorter analysis. Levels of the interleukin-1 receptor antagonist (IL-1 RA), the soluble tumor necrosis factor receptor inhibitor (sTNF-p55) and G-CSF were measured by ELISA. RESULTS: In the treatment group, 12 h after G-CSF application, neutrophil count increased, neutrophil activation marker CD11b was stimulated (CD11b: 48.6+/-9.7 vs. 71.2+/-17.7, p<0.01), neutrophil apoptosis decreased (apoptosis: 1.36+/-0.27 vs. 0.2+/-0.12%, p <.01) and the concentration of IL-1RA and sTNF-p55 increased (IL-1RA 136.4+/-72.2 vs. 340.1+/-194.6 ng/ml, p<0.01; sTNF-p55,382+/-4,243 vs. 632+/-4,714 ng/ml, p<0.01; control group nonsignificant). These effects were not seen in the control group. CONCLUSIONS: The application of a single dose of G-CSF in patients with CAP caused a prolonged survival and increased activation of neutrophils combined with a sustained release of anti-inflammatory cytokines.

Aged↗
PubMed2005

Fatal outcome of a hyperinfection syndrome despite successful eradication of Strongyloides with subcutaneous ivermectin.

We report the case of a 77-year-old man who developed a Strongyloides hyperinfection syndrome following immunosuppressive therapy more than 60 years after he moved away from an area endemic for Strongyloides stercoralis. Successful eradication of the nematode was achieved with an off label subcutaneous formulation of ivermectin. However, the patient subsequently died from acute respiratory distress syndrome (ARDS). Despite a high wormload in the stool and sputum of the patient and delayed infection control measures in the hospital, testing of the medical staff revealed a very low risk of Strongyloides transmission among healthcare workers.

Aged↗
PubMed2004

[Acute exacerbation of COPD].

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often develop into emergency situations that are associated with high morbidity and mortality. There is still a lack of a generally accepted definition for the risk stratification in AECOPD to guide an optimal diagnosis and treatment. In this article we propose a classification based on 4 degrees of severity, depending on whether outpatient treatment can be done by the patient himself or is provided by a physician and whether inpatient treatment is carried out on a general ward or on an intensive care unit. The pharmacological therapy of AECOPD relies on short acting bronchodilators, systemic corticosteroids and in case of purulent sputum on antibiotics. Longacting beta(2)-agonists or anticholinergics, theophyllin, mucolytic drugs or mechanical percussion to the chest by a physiotherapist have no proven value in the emergency treatment of AECOPD. In respiratory failure the use of oxygen therapy and non-invasive positive pressure ventilation (NIPPV) can often prevent the need for endotracheal intubation and controlled mechanical ventilation, thus preventing associated risks like the development of nosocomial pneumonia.

Acute Disease↗
PubMed2004

HOPE technique enables Western blot analysis from paraffin-embedded tissues.

In contrast to the spectrum of biochemical analyses of fresh material, that of archived specimens is widely restricted. Fixation of specimens with formalin, the most commonly used fixative, usually prevents further molecular analysis, since it leads to degradation of nucleic acids and denaturation of the antigenic determinants of proteins. To overcome these problems, the Hepes-glutamic acid buffer mediated Organic solvent Protection Effect (HOPE)-fixation technique has been developed, which preserves nucleic acids and antigenic determinants of proteins, thus expanding the applicability of immunohistochemical methods. In this study, we investigated whether HOPE-fixed tissue can be analyzed by Western blotting. Furthermore, a comparison with conventionally fixed and frozen material was made. The specimens used were tumor-free and obtained from lobectomies for lung cancer. All four antibodies tested, i.e., antibodies specific for focal adhesion kinase, surfactant protein A, PI-3-kinase, and IKKalpha, worked well if used for immunoblotting of HOPE-fixed and frozen tissue. By contrast, these antibodies showed no or only very weak specific binding if formalin-fixed specimens were analyzed. Our findings show that HOPE fixation maintains the antigenicity of proteins better than formalin fixation. The possibility for performing Western blotting with archived paraffin-embedded specimens extends the options for diagnostic and scientific analyses of fixed tissues.

Blotting, Western↗
PubMed2003

[Tuberculosis-current therapeutic principles].

Chemotherapy for tuberculosis is indicated in case of disease as well as in latent tuberculosis infection. Standard medication for drug-susceptible tuberculosis consists of isoniazid and rifampicin for six months with additional pyrazinamide and ethambutol for the first two months. Prolonged treatment is necessary in cases of cavernous pulmonary tuberculosis with lack of negative cultures by two months of therapy, in tuberculosis of the central nervous system and in some cases of superficial lymph node disease. Especially in multiple-drug resistant tuberculosis prolonged treatment with three or more drugs, that have been proven to be effective by susceptability testing, is mandatory. Attention must be payed to reliable delivery of chemotherapy as well as to side effects of antituberculosis medications. The classical treatment for latent tuberculosis infection is isoniazid. Multidrug short-course therapy, which has been shown to be equally effective, enhances patients' compliance, but toxicity is increased.

Animals↗
PubMed2003

Severe acute respiratory syndrome: global initiatives for disease diagnosis.

We present a retrospective analysis of the available articles on severe acute respiratory syndrome (SARS) published since the outbreak of the disease. SARS is a new infectious disease caused by a novel coronavirus. Originating in Guangdong, Southern China, at the end of 2002, it has spread to regions all over the world, affecting more than 8000 people. With high morbidity and mortality, SARS is an important respiratory disease which may be encountered world-wide. The causative virus was identified by a WHO-led network of laboratories, which identified the genome sequence and developed the first molecular assays for diagnosis. For the respiratory physician, detecting SARS in its earliest stages, identifying pathways of transmission, and implementing preventive and therapeutic strategies are all important. The WHO and the CDC have published helpful definitions of 'suspected' and 'probable' cases. However, the symptoms of the disease may change, and laboratory tests and definitions are still limited. Even in a situation of no new cases of infection, SARS remains a major respiratory health hazard. As with influenza virus outbreaks, new epidemics may arise at the end of each year.

Antibodies, Viral↗
PubMed2002

Inhibition of granulocyte activation by surfactant in a 2-yr-old female with meningococcus-induced ARDS.

Activated polymorphonuclear neutrophils (PMNs) play a crucial role in acute respiratory distress syndrome (ARDS) via extracellular release of reactive cell products such as elastase. Surfactant has proved valuable in restoring lung function in ARDS. The significance of its immunomodulatory properties with respect to this effect has not yet been clarified. The aim of the present study was to determine the anti-inflammatory effects of surfactant administration in an infant with ARDS. During the acute phase of ARDS in a 2-yr-old female, levels of PMN-derived elastase complexed with alpha1-protease inhibitor (E-alpha1PI) were measured in both arterial and central venous blood samples obtained simultaneously. The results were correlated with oxygen demand and plasma concentrations of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) after endotracheal administration of surfactant (Alveofact 60 mg x kg x body weight(-1)). In the present case, for the first time, a higher E-alpha1PI concentration was detected in arterial blood (4.51 mg x L(-1)) than in central venous blood (2.28 mg x L(-1)). After administration of surfactant, these concentrations and the arteriovenous difference decreased, indicating that during ARDS, most PMN degranulation takes place in the pulmonary vascular bed and is inhibited by surfactant administration. Simultaneously, TNF-alpha and IL-6 plasma concentrations decreased within hours and lung function was restored. This local inhibition of polymorphonuclear neutrophil activation by exogenous surfactant may play a key role in the early improvement in lung function after surfactant administration.

Child, Preschool↗
PubMed2001

Cannabis induced dopamine release: an in-vivo SPECT study.

In a research study aimed at examining the alterations in dopaminergic function in schizophrenia, the authors identified a surreptitious case scenario which provided new insights into the subjective and neurochemical effects of cannabis. A 38-year-old drug-free schizophrenic patient took part in a single photon emission computerized tomographic (SPECT) study of the brain, and smoked cannabis secretively during a pause in the course of an imaging session. Cannabis had an immediate calming effect, followed by a worsening of psychotic symptoms a few hours later. A comparison of the two sets of images, obtained before and immediately after smoking cannabis, indicated a 20% decrease in the striatal dopamine D2 receptor binding ratio, suggestive of increased synaptic dopaminergic activity. This observation offers a plausible biological explanation for the psychotogenic effects of cannabis in vulnerable individuals, and also raises speculations about an interaction between cannabinoid and dopaminergic systems in the brain reward pathways.

Adult↗
PubMed2001

A new radiocolloid for sentinel node detection in breast cancer.

BACKGROUND: The optimal radioactive tracer and technique for sentinel lymph node localization in breast cancer is yet to be determined. The dilemma of small particle size with dispersion to second echelon nodes versus failure of migration of larger radiocolloids needs to be resolved. A new radiocolloid preparation with particle size under 0.1 micron was developed with excellent primary/post lymphatic entrapment ratio. OBJECTIVE: To assess the feasibility of a new 99mTc radiocolloid cysteine-rhenium colloid in sentinel lymph node (SLN) localization for breast cancer. METHODS: Forty-seven patients with newly diagnosed T1 or T2 breast cancer underwent injection of 99mTc-labeled cysteine-rhenium colloid followed by lymphoscintigraphy. Same day SLN biopsy with patent blue dye and intraoperative gamma probe to identify SLNs were performed. RESULTS: SLN mapping and intraoperative localization were successful in 46/47 (98%) of patients. The blue dye radioactive tracer concordance was 94%. There was one false-negative in a patient with a nonpalpable tumor that underwent ultrasound-guided peritumoral radiocolloid injection. CONCLUSIONS: 99mTc-cysteine-rhenium colloid is highly effective in identifying SLNs. It has the advantage of smaller particle size than sulfur colloid with easier lymphatic migration. It has a more neutral pH with less pain on injection and does not require filtration, thereby minimizing radiation exposure to technologists.

Animals↗
PubMed2001

Subjective effects of AMPT-induced dopamine depletion in schizophrenia: correlation between dysphoric responses and striatal D(2) binding ratios on SPECT imaging.

Approximately one third of schizophrenic patients treated with neuroleptic drugs experience unpleasant subjective responses, that are collectively known as neuroleptic dysphoria. Experimental research in animals indicates that drug induced dopaminergic blockade in mesolimbic circuits, especially the nucleus accumbens, leads to impaired pleasure responsivity and dysphoria. The present study tested this putative mechanism in drug-free schizophrenic patients (n = 12), through inducing dysphoric responses with alphamethyl paratyrosine (AMPT) and simultaneously quantifying their baseline striatal dopmine (D(2)) function with (123)IBZM-SPECT imaging. Results showed a wide variability in the occurrence and severity of dysphoric responses, clearly distinguishing a dysphoric group from non-dysphoric responders. Severity of dysphoric responses, measured by standardized rating scales, correlated inversely with changes in D(2) receptor binding ratios (r = +0.82, p <.01). These results support the notion that striatal dopaminergic activity is not uniformly elevated in all schizophrenic patients, and the sub-group of individuals with lower baseline dopamine function are at an increased risk for dysphoric responses during antipsychotic therapy with dopaminergic blocking drugs.

Adult↗
PubMed2001

Tumor necrosis factor-alpha -308 promoter gene polymorphism and increased tumor necrosis factor serum bioactivity in farmer's lung patients.

Hypersensitivity pneumonitis (HP) represents an immunologic reaction of the pulmonary parenchyma to an inhaled agent. Since tumor necrosis factor (TNF)-alpha is thought to be involved in the pathogenesis of HP, and polymorphisms in the TNF genes have been associated with variations in the production of TNF-alpha, we investigated the serum bioactivity and genotype of TNF in HP. TNF bioactivity was measured after hay dust challenge in eight patients with farmer's lung (Group A) and in 12 healthy, sensitized (antibody-positive) controls (Group B). Genotyping for the -308 TNF-alpha promoter polymorphism and the TNF-beta intron 1 gene polymorphism was performed in 20 patients with farmer's lung, 25 patients with pigeon breeder's lung, and 216 controls. TNF bioactivity increased in Group A at 4 to 10 h after hay dust challenge, but not in Group B (p < 0.05). The frequency for the TNFA2 allele, a genotype associated with high TNF-alpha production in vitro, was significantly higher in farmer's lung patients (frequency [f] = 0.43, p = 0.0012) than in controls (f = 0.19) or patients with pigeon breeder's lung (f = 0.16). Genotyping for TNF-beta revealed no significant abnormalities. Thus, increased production of TNF-alpha after hay contact, and a genetic predisposition to TNF-alpha production, are implicated in the pathogenesis of alveolitis in farmer's lung.

Adult↗
PubMed2000

Integrated cytogenetic map of chromosome arm 4S of A. thaliana: structural organization of heterochromatic knob and centromere region.

We have constructed an integrated cytogenetic map of chromosome arm 4S of Arabidopsis thaliana. The map shows the detailed positions of various multicopy and unique sequences relative to euchromatin and heterochromatin segments. A quantitative analysis of the map positions at subsequent meiotic stages revealed a striking pattern of spatial and temporal variation in chromatin condensation for euchromatin and heterochromatin. For example, the centromere region consists of three domains with distinguishable structural, molecular, and functional properties. We also characterized a conspicuous heterochromatic knob of approximately 700 kb that accommodates a tandem repeat and several dispersed pericentromere-specific repeats. Moreover, our data provide evidence for an inversion event that relocated pericentromeric sequences to an interstitial position, resulting in the heterochromatic knob.

Arabidopsis↗