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Biomedical subjects

G P Tilz

Publications and source records attributed to G P Tilz.

At least 19 recordsLinked to original sources

[Sense and nonsense in antibiotic therapy for respiratory tract infections].

Whether an antibiotic successfully eradicates pathogens depends on the pathogens involved, on pharmacokinetics and bioavailability in the target tissue, and on the antimicrobial resistance of the pathogen. Other determinants are drug interactions, individual risk factors, age and compliance with respect to correct dosage and duration of therapy. In many cases, antimicrobial therapy is begun on an empirical basis, because the responsible pathogen can be identified in only half of all respiratory infections. The eradication of the pathogen has to be the first aim if treatment is to be curative and the development of resistance prevented. Long-term prevention of antimicrobial resistance will require a more critical prospective evaluation of the prescription of antibiotics. This paper considers rational and irrational measures in the antimicrobial therapy of respiratory infections.

Anti-Bacterial Agents↗

Detection of tumour cells in the peripheral blood of patients with breast cancer. Development of a new sensitive and specific immunomolecular assay.

Malignant cells in the peripheral blood of patients with solid tumours are of considerable importance for the prognosis and therapeutic correlation. Their detection however is difficult due to lack of sensitivity, specificity and technical problems in standardisation. In this original article we show a new sensitive method overcoming the hitherto known difficulties by combining traditional antibody-techniques with a RT-PCR. Due to this method 2 tumour cells within 5 ml of peripheral blood can be detected in spiking experiments.

Breast Neoplasms↗

Cardiac myxomas: 24 years of experience in 49 patients.

OBJECTIVES: In this single-center study we reviewed our experience with a significant number of cardiac myxoma cases occurring over the past two decades. PATIENTS AND METHODS: Cardiac myxomas represented 86% of all surgically treated cardiac tumors at our center. Specifically, there were 49 consecutive patients, each with at least one myxoma. A detailed clinical, immunological, and echocardiographic long-term examination of 37 patients revealed one recurrent myxoma. RESULTS: Most myxomas originated from the left atrium (87.7%), but also much less frequently from the mitral valve (6.1%), from the right atrium (4.1%), and from the left and right atria (2.0%). The myxomas produced a prolapse into the left ventricle in 40.8% of the patients, mitral stenosis in 10.2%, and threatened left ventricular outflow tract obstruction in 2.0%. Multiple myxomas were found in 20.4% of the patients. Cardiac signs appeared in 93.9% of the patients. Preoperative embolic events had occurred in 26.5%. Immunologic alterations were present in 87.5%. For resection, a bilateral atriotomy was used. An additional aortotomy was needed to expose one mitral valve myxoma. Postoperatively, 81.1% of the patients remained without cardiac symptoms. The early mortality rate was 2.0% and the late mortality rate was 6.1%. Long-term prognosis was excellent with an actuarial survival rate of 0.74. Specific immunologic alterations were found in 71.4% of the patients. The actuarial freedom from reoperation of the myxoma was 0.96. The rate of reoperations was low with 2.0% after 24 years. CONCLUSIONS: Myxomas were usually detected and operated on in symptomatic patients. A high index of suspicion seems important for early diagnosis. Immunologic findings may play an additional role in confirming the diagnosis and the recurrence of a myxoma. Immediate surgical treatment was indicated because of the high risk of embolization or of sudden cardiac death. Also, a familial genesis must be excluded in myxoma patients.

Adult↗

Ultrasensitive detection and identification of fluorescent molecules by FCS: impact for immunobiology.

An experimental application of fluorescence correlation spectroscopy is presented for the detection and identification of fluorophores and auto-Abs in solution. The recording time is between 2 and 60 sec. Because the actual number of molecules in the unit volume (confocal detection volume of about 1 fl) is integer or zero, the fluorescence generated by the molecules is discontinuous when single-molecule sensitivity is achieved. We first show that the observable probability, N, to find a single fluorescent molecule in the very tiny space element of the unit volume is Poisson-distributed below a critical bulk concentration c*. The measured probability means we have traced, for example, 5 x 10(10) fluorophore molecules per ml of bulk solution. The probability is related to the average frequency, C, that the volume of detection contains a single fluorescent molecule and to the concentration, c, of the bulk solution. The analytical sensitivity of an assay is calculated from the average frequency C. In the Goodpasture experiment, we determined as analytical sensitivity a probability of 99.1% of identifying one single immune complex. Under these conditions, a single molecule event is proven. There exist no instrumental assumptions of our approach on which the experiment itself, the theoretical background, or the conclusion are based. Our results open up a broad field for analytics and diagnostics in solution, especially in immunology.

Anti-Glomerular Basement Membrane Disease↗

Unilateral high-altitude pulmonary edema (HAPE): a case report and discussion of pathophysiology.

High-altitude pulmonary edema (HAPE), a potentially life-threatening altitude adaptation disorder, is considered to be caused by an exaggerated increase in pulmonary blood pressure and a non-cardiogenic rise in pulmonary vascular permeability subsequent to alveolar hypoxia. A 40-year-old male mountaineer was affected by an advanced stage of HAPE at high altitude (Monte Rosa plateau, 4000 m). The symptoms abated immediately after the patient descended from the altitude. However, six hours after the symptoms had resolved, radiographic signs of pulmonary edema, confined to the right lung, were seen. This rarely described unilateral radiological pattern of HAPE resolved completely within two days. We suggest that aspiration events of nasal secretion, the right sleeping position at night and an elevated right diaphragm reduced the patient's compensatory hyperventilation capacity of the right lung. The resulting increased alveolar hypoxia in the right lung was responsible for unilateral edema. The pathophysiological mechanism underlying unilateral HAPE is discussed.

Adult↗

[Soluble receptors of TNF-alpha in rheumatoid arthritis].

The serum level of soluble TNF-alpha receptors with molecular mass 55 kDa (sTNF-a55R) was measured by enzyme immunoassay with commercial kits in 30 patients with rheumatoid arthritis (RA) and 38 healthy donors. High sTNF-a55R serum levels were registered in 90% of RA patients. These levels correlated with RA activity by DAS. Thus, assay for sTNF-a55R can be used for assessing RA activity.

Antirheumatic Agents↗

Tryptophan degradation and immune activation in Alzheimer's disease.

Alzheimer's disease (AD) is likely associated with systemic immune activation. During immune response, interferon-gamma stimulates indoleamine 2,3-dioxygenase (IDO) converting tryptophan to N-formylkynurenine followed by kynurenine in an ensuing step. Thus, IDO activity is estimated by the kynurenine per tryptophan quotient (Kyn/Trp). In 21 patients suffering from AD, in 20 controls of similar age, and in 49 blood donors we measured serum tryptophan and kynurenine concentrations by HPLC. Lower tryptophan concentrations were found in elderly control subjects compared to blood donors (62.1 vs. 73.0 microM, p < 0.005). Tryptophan concentrations tended to be still lower in AD patients (54.4 microM, p = 0.07) compared to elderly controls. Enhanced tryptophan degradation in patients was reflected by significantly increased Kyn/Trp (46.1 vs. 34.1 in elderly controls, p < 0.05). Correlations were found in patients between Kyn/Trp and concentrations of soluble immune markers in serum, i.e., neopterin, interleukin-2 receptor and tumor necrosis factor receptor (all p < 0.001). Increased Kyn/Trp was associated with reduced cognitive performance. Tryptophan degradation due to immune activation may exert impact on the pathogenesis of AD.

Adult↗

[Function and repertoire of the immune system in body's defense].

This is a minireview on the organisation and activity of the human immune system with special reference to sport and--more precisely--stress by mountaineering. The activation of the immune system under physical exercise is shown and the immune depression after the sport documented. Hence the conclusion of increased susceptibility to diseases in the post activation phase--a sort of depression after alpine sport.

Altitude↗

Degradation of tryptophan in neurodegenerative disorders.

In patients with neurodegenerative disorders, namely Alzheimer's disease and Huntington's disease, we compared serum concentrations of tryptophan, kynurenine and the kynurenine per tryptophan ratio with concentrations of soluble immune activation markers. Significantly lower tryptophan concentrations were observed in the patients, and lower tryptophan levels as well as higher kynurenine levels and higher kynurenine per tryptophan ratios correlated with higher concentrations of neopterin, and soluble receptors for TNF and interleukin-2. In both groups of patients tryptophan concentrations correlated inversely with the degree of mental retardation. No such association existed for the duration of the disease. The data show that systemic chronic immune activation in patients with Alzheimer's disease and Huntington's disease is associated with significant degradation of tryptophan, which is most likely due to activation of indoleamine (2,3)-dioxygenase by immunologic stimuli. Further studies will be necessary to investigate a potential role of tryptophan degradation in the pathogenesis of neurodegenerative disorders.

Alzheimer Disease↗

[Frequency of immunologic disorders in acute schizophrenia].

Immunological examinations in schizophrenic patients have shown that there are many alterations in both arms of the immune system, i.e. cellular and humoral activities. The results are quite heterogeneous, as not even all schizophrenics show these pathological changes. Immunological findings are assumed to be etiopathogenetically related to the disease process or to be an epiphenomenon. The present study supposes that immunological alterations as they can be found during the course of schizophrenia may be an indicator for somatic vulnerability or an epiphenomenon. 60 male inpatients, fulfilling DSM-IV criteria of schizophrenia where examined during their acute phases of psychosis and during their phases of clinical improvement, by means of a serological profile including cellular and humoral parameters. The control group consisted of 42 healthy male volunteers. It was the aim of this study to find out if there were (a) overall differences in the immune profiles between patients and control group and (b) differences between different categories of schizophrenic disorder. During the acute phase nearly half of the schizophrenic patients showed pathologic immunological parameters, whereas none of the controls did. During the phase of clinical improvement the number of patients with normal immunological findings predominated. Furthermore there was a difference between the Paranoid and the Disorganized Subtype, the latter showing more immunological abnormalities. The results of this study give further support to the hypothesis that immunological aberrations should not be seen as closely etiopathogenetically related to schizophrenic disorders, but rather as an epiphenomenon (e.g. as a stress marker) and/or as indicators for somatic vulnerability.

Acute Disease↗

Relation of serial measurements of plasma-soluble intercellular adhesion molecule-1 to severity of acute pancreatitis.

OBJECTIVE: Acute pancreatitis remains a clinical challenge because it is difficult to predict whether, in a given patient, the disease will be mild or will run a severe course with a possibly fatal outcome. The aim of this study was to investigate whether circulating soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of leukocyte activation is related to the severity of the disease. METHODS: The study included 29 consecutive adults admitted with acute pancreatitis. Plasma sICAM-1 levels were measured serially over a period of 6 days, and values and time courses were correlated with clinical severity. RESULTS: Our patients fell into four groups on the basis of the following measurements: 1) Decreasing sICAM- levels with maximal values of 446 +/- 90 ng/ml (mean +/- SEM) slightly above the upper limit of normal were associated with uncomplicated mild disease in seven patients. 2) In nine patients with sICAM-1 concentrations reaching a peak of 743 +/- 121 ng/ml after 3 days, severe pancreatitis was present in 11% and pancreatic necrosis occurred in 33%. 3) A second increase of sICAM-1 (maximal level: 993 +/- 169 ng/ml) after an initial decrease (relapsing pattern, 7 patients) was associated with a severe course of disease in 71% including pancreatic necrosis in 43% and nosocomial pneumonia in 42%. 4) A rapid increase of sICAM-1 reaching highest maximal values of 1738 +/- 104 ng/ml (p < 0.0001) indicated fulminant pancreatic necrosis and a fatal outcome in six patients. CONCLUSIONS: Serial plasma sICAM-1 levels in patients with acute pancreatitis within the first 6 days after admission fall into four different groups of severity according to the shape of the curves. This suggests that the time course of elevated plasma sICAM-1 concentrations reflects the risk of developing necrosis and clinical complications in acute pancreatitis.

Acute Disease↗

Increased serum neopterin concentrations in patients with Alzheimer's disease.

We measured serum neopterin concentrations in 24 patients with Alzheimer's disease (8 males, 16 females; age: 73.1+/-6.2 years; free of any infectious process) and fourteen controls of similar age (4 males, 10 females; age: 69.7+/-8.8 years). Compared to controls, significantly higher concentrations of neopterin (p< 0.01) were found in patients with Alzheimer's disease. Among patients, concentrations of neopterin were higher in those with lower mini-mental-state (p < 0.05), and an inverse correlation existed between mini-mental-state and neopterin concentrations. No such association existed with the duration of the disease. There were also significant correlations between neopterin and serum concentrations of immune activation markers such as soluble tumor necrosis factor (TNF) receptor and soluble interleukin-2 receptor (all p<0.01). Thus, increased concentrations of neopterin in serum of patients with Alzheimer's disease correlate with the severity of dementia. The data imply a chronic state of peripheral immune activation in Alzheimer's disease.

Aged↗

[Soluble adhesion molecules (P-selectin, ICAM-1 and ICAM-3) in rheumatoid arthritis].

AIM: Investigation of serum levels and clinical role of soluble intercellular molecules of adhesion (pICAM-1, PICAM-3 and pP-selectin) in rheumatoid arthritis (RA). MATERIALS AND METHODS: Enzyme immunoassay with Bender MedSystem kits (Austria) was employed to measure serum concentration of soluble intercellular molecules of adhesion in 36 RA patients. RESULTS: Elevated levels of serum pICAM-1, pICAM-3 and pP-selectin were registered in 74.2, 28.6 and 25.7% of RA patients, respectively. Content of pP-selectin more strongly correlated with activity and severity indices than that of pICAM-3 (p < 0.001). Content of pICAM-1 and clinical picture of RA were unrelated. CONCLUSION: Levels of pP-selectine can characterize RA activity.

Adolescent↗

[Systemic changes of the immune system in patients with Alzheimer's dementia].

OBJECTIVE: The etiology of Alzheimer's disease (AD) is still unknown. Recent investigations have shown that immune and inflammatory mechanisms could be of importance in the pathophysiology of AD. In this study 10 different immune parameters were measured to further investigate immunological changes in AD. PATIENTS AND METHODS: In 30 randomized patients with AD (20 females and ten males aged 74.5 +/- 6.5 years) as well as 13 controls aged 70.7 +/- 8.4 years, mostly relatives of the patients, all free of acute infection, serum concentrations of IgA, IgG, IgM, C3, C4, circulating immune complexes, sCD23, cardiolipin and the soluble cytokine receptors interleukin 2-receptor (sIL2-R) and tumor necrosis factor-receptor (sTNF-R) were measured. Diagnosis of AD was made according to NINCDS/ ADRDA criteria. The degree of dementia was determined by Mini-Mental-State-Examination (MMSE). RESULTS: Compared to the control group, patients with AD had significantly increased IgA (369,3 +/- 160,9 mg/dl vs 253.5 +/- 101.8 mg/dl [P = 0.02]), sCD23 [207.4 +/- 217.7 I. U./ml vs 80.6 +/- 35.5 I. U./ml [P = 0.004]), sIL2-R (829.6 +/- 742.1 I. U./ml vs 299.7 +/- 168.5 I. U./ml [P = 0.001]) and sTNF-R (4.6 +/- 2.0 I. U./ml vs 2.9 +/- 1.1 I. U./ml [P = 0.001]) levels. A negative correlation was seen between MMSE and sTNF-R (r = -0.34; P < 0.05). CONCLUSION: These findings indicate a chronic state of immune activation in AD and support the hypothesis of immune mediated mechanisms as part of the pathogenesis of AD. Prospective studies of the effect of anti-inflammatory drugs on the progression of AD will be needed.

Aged↗