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Biomedical subjects

S Krüger

Publications and source records attributed to S Krüger.

At least 55 records · Page 3Linked to original sources
PubMed2002

[Impairment of ventilatory parameters and exercise capacity in patients with pulmonary hypertension and chronic heart insufficiency].

BACKGROUND AND OBJECTIVE: Chronic heart failure often coincides with secondary pulmonary hypertension. In this study the influence of pulmonary hypertension on exercise capacity and ventilatory parameters in patients with chronic heart failure was examined. PATIENTS AND METHODS: 21 patients with chronic heart failure (six women, 15 men, mean age 55 +/- 10 years) and a left ventricular ejection fraction of 25 % +/- 5 % were studied by right heart catheterization, bodyplethysmography including carbonmonoxide diffusion testing and spiroergometry. Seven patients suffered from ischemic and 14 patients from dilative cardiomyopathy. Pulmonary hypertension (defined as pulmonary artery mean pressure > 25 mmHg) was found in ten patients. RESULTS: Patients with pulmonary hypertension showed a reduced vital capacity (75 % +/- 20 % of normal values vs. 93 % +/- 14 % of normal values, p < 0.001), a lower forced expiratory volume in one second (FEV1 68 % +/- 21 % of normal values vs. 91 % +/- 15 % of normal values, p < 0.001), and a reduced carbonmonoxide-diffusing capacity (58 % +/- 21 % vs. 77 % +/- 21 %, p < 0.001) compared to patients without pulmonary hypertension. Mean expiratory flow at 25 % and 75 % of the exspiration time was lower in patients with pulmonary hypertension (30 % +/- 13 % vs. 50 % +/- 29 % and 62 % +/- 25 % vs. 81 % +/- 20 %, each p < 0.05). In patients with pulmonary hypertension, the flow-volume diagram characteristically showed signs of "small airway disease". Spiroergometry revealed a significantly lower maximum oxygen-uptake (12.5 +/- 2.1 vs. 15.2 +/- 4.1 ml/min/kg, p < 0.05), oxygen-uptake at the anaerobic threshold (9.7 +/- 1.6 vs. 12.0 +/- 3.0 ml/min/kg, p < 0.05), carbon dioxide ventilatory efficiency (EqCO2 38 +/- 9 vs. 31 +/- 3, p < 0.05) and ventilatory reserve (39 % +/- 22 % vs 51 % +/- 21 %, p < 0.05) in patients with pulmonary hypertension. CONCLUSION: In patients with chronic heart failure the presence of pulmonary hypertension leads to a reduction of exercise capacity and impaired ventilatory parameters. Lung functional testing reveals bronchial obstruction, "small airway disease" and a reduced ventilatory efficiency.

Cardiac Catheterization↗
PubMed2002

Expression of cathepsins B, H, K, L, and S during human fetal lung development.

Cathepsins are involved in lysosomal protein degradation, proenzyme activation, antigen processing, and hormone maturation. They are secreted by tumor cells and macrophages and catalyze the remodeling of extracellular matrix proteins. To gain insight into the expression pattern of cathepsins during fetal lung development, the expression of cathepsins B, H, K, L, and S at protein and mRNA levels were evaluated by using immunohistochemistry and in situ hybridization. Early expression of cathepsins B, H, and K was found in epithelial cells of the branching presumptive bronchi (<12th week of gestation). The most intense cathepsin K-specific immunoreactivity was found in developing airways with a lumen. Cathepsin K was found in epithelial cells only, whereas in contrast, cathepsins B and H were detected both in epithelial and interstitial cells. During fetal maturation, interstitial cells displayed cathepsin L immunoreactivity and, in the saccular phase (>26th week of gestation), both cathepsin L and S immunoreactivities. A continuous decline in the proportion of cathepsin H-positive interstitial CD68-positive cells was observed. These discrete temporal and spatial variations in cathepsin expression during organogenesis of the human lung indicate different physiological roles for the individual enzymes in different cell types and developmental stages.

Antigens, CD↗
PubMed2002

[Psychopharmacotherapy of bipolar affective diseases].

The broadening of the classification systems for manic-depressive illness towards a spectrum of bipolar disorders implicates a more differentiated use of pharmacotherapies. However, many questions still remain open. This implies that all consensus guidelines and recommendations have to be considered as preliminary. On the other hand, research in the last decade has developed many new treatment alternatives, both for mood stabilizers and antidepressants as well as antipsychotics. These recommendations, which have been developed in the process of two consensus meetings, try to consider the broadening of the concept of bipolar disorder by differentiating between subgroups according to acute symptomatology and characteristics of the long-term course, e.g., rapid cycling. In particular, the emerging role and new indications of mood stabilizing antiepileptic drugs, atypical antipsychotics, and new antidepressants will be discussed.

Antidepressive Agents↗
PubMed2002

Recurrent focal myositis of the peroneal muscles.

Recurrent focal myositis is a rare entity and can be difficult to diagnose and treat. A long-term follow-up and diagnostic evaluation was carried out in a patient who presented with ankle stiffness secondary to a painful mass within the calf. This process was diagnosed as focal myositis of the peroneal muscles, which recurred over a period of 7 yr. A review of the literature regarding focal myositis, treatment options and a successful conservative therapy regimen, as an alternative to a surgical protocol, are presented. After making the diagnosis with the help of a muscle biopsy, long-term therapy should be considered. Conservative treatment of focal myositis with anti-inflammatory drugs and physical therapy can be successful but recurrence may occur if the medical treatment is interrupted.

Adult↗
PubMed2002

Prevention and treatment of peritoneal carcinomatosis in experimental investigations with CPT-11 and oxaliplatin.

Following surgical resection of colorectal carcinoma, local recurrence in the tumor bed or in the mesentery remains a frequently encountered problem. Currently there are no recognized standard therapy protocols for the prevention of local recurrence or the treatment of peritoneal carcinomatosis. The aim of our trial was to investigate whether CPT-11 and oxaliplatin could decrease i.p. tumor growth in a basic experimental animal model. Experiments were performed on three groups of animals plus controls. In the first group, the cytostatic agents were applied directly following tumor cell implantation into the peritoneal cavity. In the second group, early postoperative i.p. chemotherapy (days 5, 10 and 15 following surgery) was administered. In the third group, late i.p. chemotherapy (days 15, 20 and 25 after tumor cell transfer) was administered with the intention of reducing a manifest peritoneal carcinomatosis. The trial also set out to describe any side effects observed following i.p. administration. The results indicated that CPT-11 and oxaliplatin were highly effective in reducing i.p. tumor spread after direct i.p intraoperative application. Intraperitoneal administration of CPT-11 or oxaliplatin also decreased i.p. tumor growth after early i.p. chemotherapy. CPT-11 was a little more effective with lower side effects. However, it was clear that it was not possible to treat a manifest peritoneal carcinomatosis in this way.

Anesthesia↗
PubMed2001

Lower dopamine transporter binding potential in striatum during depression.

Previous studies suggest that there is a dopamine lowering process during major depressive episodes (MDE). To investigate this, we measured the dopamine transporter binding potential (DAT BP) in the striatum of depressed and healthy subjects using [(11)C]RTI-32 PET. The DAT, a predominantly presynaptic receptor, decreases in density after chronic dopamine depletion and the BP is proportional to receptor density. In all striatal regions, subjects with MDE had significantly lower DAT BP. Low striatal DAT BP in MDE is consistent with a downregulation of DAT in response to a dopamine lowering process. There was also a strong, highly significant, inverse correlation between striatal DAT BP and neuropsychological tests of dopamine-implicated symptoms in patients (i.e. patients with lower DAT BP performed better). Lower DAT BP itself reduces extracellular clearance of dopamine. Patients who did not decrease their striatal DAT BP failed to compensate for low dopamine and showed greater impairment on dopamine related tests.

Adolescent↗
PubMed2001

[Recurrent hypoglycemia caused by malignant insulinoma: chemoembolization as a therapeutic option].

HISTORY AND CLINICAL FINDINGS: A 73-year-old previously healthy woman presented with recurrent weakness, vertigo and perioral paresthesia of 3 months' duration. Physical examination on admission was unremarkable and revealed a patient in good condition. INVESTIGATIONS: Recurrent episodes of fasting hypoglycemia let us to proceed with a fasting test. The test was stopped after 24 hours when the patient became presyncopal and was found to have a blood sugar value of 2.2 mmol/l (accompanied by inadequately increased values for proinsulin, insulin and C-peptide). Ultrasound and computertomography of the abdomen showed a huge inhomogeneous mass in the tail of pancreas and multiple lesions in the liver, respectively. Core needle biopsies revealed typical histopathological findings of a neuroendocrine carcinoma. TREATMENT AND COURSE: Eight cycles of chemotherapy were given using streptozotocin/doxorubicin for three cycles and streptozotocin/5-fluorouracil for the remaining therapy over a period of 16 months resulting in a reduction in size of liver metastases and improvement of symptoms. Following 6 months without any therapy new episodes of severe hypoglycemia and progression of the liver metastases occurred. Despite seven further cycles of chemotherapy and additional treatment with diazoxide/octreotide the patient remained hypoglycemic and continuous glucose infusions became necessary. Therefore, chemoembolization of the liver with streptozotocin/5-fluorouracil and lipiodol-emulsion was performed. This resulted in a significant improvement of symptoms and the patient could subsequently be discharged. The patient died 4 months later. CONCLUSION: Chemoembolization is an effective possibility in the palliative treatment of advanced malignant insulinoma.

Aged↗
PubMed2001

A proteinase inhibitor decreases tumor growth in a laparoscopic rat model.

BACKGROUND: The balance between proteolysis and protease inhibition in the formation and breakdown processes of the extracellular matrix plays a major role in tumor cell invasion. An understanding of this relationship gave rise to the therapeutic concept of lowering tumor cell invasion by inhibiting protease activity. Phosphoramidon is an unspecific proteinase inhibitor. This experimental study investigated the effect of intraperitoneal phosphoramidon administration on tumor growth in a laparoscopic rat model. METHODS: In the first phase of the study, we investigated the influence of phosphoramidon on tumor cell invasion in a collagen matrix gel chamber in vitro. In a second experiment, a suspension of colon carcinoma cells (CC531) was introduced into the peritoneal cavity of male WAG rats. Prior to laparoscopy (at 6 mmHg for 20 min), the animals were randomized to two groups. At the start of laparoscopy, the test substance was applied intraperitoneally (group 1: controls, 1 ml 0.9% NaCl; group 2: 250 mg phosphoramidon in 1 ml 0.9% NaCl). Three weeks after the injection of tumor cells, the animals were autopsied and the tumor mass determined. RESULTS: In comparison with the control group (tumor weight 7.42 +/- 1.01 g), intraperitoneal tumor growth in the experimental group was significantly (p < 0.001) reduced by the application of phosphoramidon (tumor weight, 3.22 +/- 1.06 g). Phosphoramidon also significantly (p < 0.05) reduced tumor cell invasion through the matrix gel. CONCLUSION: The proteinase inhibitor phosphoramidon reduced tumor cell invasion in vitro and tumor cell growth in vivo in this laparoscopic rat model.

Animals↗
PubMed2001

Cathepsin K--a marker of macrophage differentiation?

Cathepsin K is a cysteine protease with high matrix-degrading activity. Initially, cathepsin K was described as being expressed exclusively by osteoclasts. It was suggested that cathepsin K expression is a specific feature of cells involved in bone remodelling. The aim of this study was to investigate the hypothesis that cathepsin K is expressed not only in bone-resorbing macrophages, but also more generally in specifically differentiated macrophages, such as epithelioid cells and multinucleated giant cells in soft tissues. Specimens obtained from different organs and anatomical locations of patients suffering from sarcoidosis, tuberculosis, granulomas caused by foreign materials, and sarcoid-like lesions were investigated for the expression of cathepsins B, K, and L. Immunohistochemistry and in situ hybridization showed cathepsin K in epithelioid cells and multinucleated giant cells irrespective of the pathological condition and anatomical location, but not in normal resident macrophages. By immunoelectron microscopy, cathepsin K was discovered in cytoplasmic granules of multinucleated giant cells. In contrast, cathepsin B and cathepsin L were expressed ubiquitously in CD68-positive tissue macrophages, epithelioid cells, and multinucleated giant cells. The results demonstrate that cathepsin K, but not cathepsin B or cathepsin L, differentiates specific phenotypes of macrophages independently of the anatomical site. Its enzymatic characteristics, particularly its high matrix-degrading activity, suggest that cathepsin K-positive epithelioid cells and multinucleated giant cells are characterized by an enhanced specific proteolytic capability.

Adult↗
PubMed2001

A 5-year follow-up on antibody response after diphtheria and tetanus vaccination in hemodialysis patients.

Chronic renal failure is associated with a T-cell-dependent immune defect. In the past, various studies have focused on the insufficient immune response to vaccination of hemodialysis patients. An impaired vaccination response rate has been reported for vaccines against hepatitis B, influenza, tetanus, diphtheria, and others. However, no data exist on the long-term success of vaccination against tetanus and diphtheria in these patients. The aim of the present study is to investigate seroresponse to tetanus and diphtheria vaccination over a 5-year period. Antibody levels were determined by enzyme immunoassay. Antidiphtheria antibody levels of 31 hemodialysis patients were determined 5 years after vaccination. After 5 years, 10 of 31 patients (32%) had a protective antibody level against diphtheria (>/=0.1 IU/mL), whereas 12 months after vaccination, 26 of 71 patients (37%) were protected. Also, mean antibody levels significantly decreased. Furthermore, antitetanus antibody levels of 21 patients simultaneously vaccinated against tetanus and diphtheria were investigated. After 5 years, 15 of 21 patients (71%) were protected compared with 46 of 71 patients (65%) in the hemodialysis collective studied after 12 months. In the interval between 1 and 5 years after vaccination, significantly more patients in the initial nonresponder group had died than in the responder group; therefore, the overall protection rate observed in vaccinated patients increased. Our results provide evidence that during a 5-year period, antibody persistence against tetanus toxoid is better than that against diphtheria toxoid. Therefore, detection of individual antibody concentrations may be indicated to decide on revaccination.

Antibodies, Bacterial↗
PubMed2001

[Anxiety: an aspect of the interaction of doctor and patients on the waiting-list and after lung-transplantation].

Anxiety occurs frequently in patients who are on the waiting-list for a lung-transplantation or have already been transplanted. In this context anxiety is a theme of every interaction of doctor and patient but often remains unrecognized because it hides behind bodily symptoms and mechanisms of defense. Anxiety affects patients' behavior and compliance and may afflict - especially if not recognized - doctors' decisions and thus patients' health and survival. It is therefore necessary to recognize and to openly handle anxiety in the interaction of doctor and patient.

Adaptation, Psychological↗
PubMed2001

Ulcerative colitis and colorectal carcinoma: DNA-profile, laminin-5 gamma2 chain and cyclin A expression as early markers for risk assessment.

BACKGROUND: Ulcerative colitis patients are at increased risk for developing colorectal carcinomas. Despite expensive surveillance programmes, clinical practice reflects an uncertainty in individual risk assessment. The aim of the study was to evaluate independent cellular features with possible predictive value. METHODS: Two patient groups were selected: group A comprised 8 patients with ulcerative colitis-associated colorectal carcinomas, group B comprised 16 ulcerative colitis patients with risk factors (duration of disease, extent of inflammation, epithelial dysplasias). A total of 683 paraffin-embedded mucosal biopsies were retrospectively evaluated for inflammatory activity, grade of dysplasia, ploidy status, laminin-5 gamma2 chain and cyclin A expression. RESULTS: Mild or moderate inflammatory activity was present in 78% of all biopsies, low- or high-grade dysplasia in 5.5%. There was no difference in inflammatory activity and dysplasia between patient groups. In group A, 75% of the biopsies exhibited aneuploid DNA distribution patterns. Group B showed mainly proliferative-diploid cell populations (85% / P = 0.006). Laminin-5 gamma2 chain was expressed in 13% of all biopsies, with a higher frequency in group A (P = 0.002). Cyclin A expression was found in 98% of all biopsies, with a higher number of immunopositive cells in group A biopsies (P = 0.014). CONCLUSIONS: Combined nuclear DNA assessment, laminin-5 gamma2 chain and cyclin A expression may help to identify ulcerative colitis patients with an increased risk for cancer development.

Adult↗
PubMed2001

1,25-dihydroxyvitamin D3 differentially regulates IL-1alpha-stimulated IL-8 and MCP-1 mRNA expression and chemokine secretion by human primary proximal tubular epithelial cells.

Beside its role in calcium homeostasis, 1,25-D3 modulates multiple immunological functions in cells of the immune system. In tubular epithelial cells, it increases the expression of HLA-DR and ICAM-1 molecules. Since production of chemokines, such as IL-8 and MCP-1, by tubular epithelial cells is crucial for the inflammatory response in acute transplant rejection and interstitial nephritis, we tested whether 1,25-D3 influences the production of IL-8 and MCP-1 by primary human tubular epithelial cells (TEC). For chemokine detection we used enzyme-linked immunosorbent assays. We differentiated between chemokine secretion directed to the apical and basolateral environment by using cell culture inserts as a model for the tubular basement membrane. mRNA of IL-8 and MCP-1 after stimulation of TEC with IL-1alpha and/or 1,25-D3 was isolated and compared by competitive RT-PCR. We found that basolateral production of IL-8 was higher than luminal secretion. 1,25-D3 (10(-8) M) alone and in combination with IL-1alpha suppressed IL-8 production after 48 h. Basolateral compared to luminal MCP-1 secretion was higher after stimulation either with IL-1alpha alone or combined with 1,25-D3. After 72 h, 1,25-D3 enhanced the IL-1alpha-stimulated MCP-1 secretion. Increased IL-8 mRNA expression after stimulation with IL-1alpha was suppressed by coincubation with 1,25-D3, while MCP-1 mRNA synthesis was enhanced by 1,25-D3 alone and in combination with IL-1 alpha. We conclude that 1,25-D3 differently modulates the expression of CXC-chemokine IL-8 and CC-chemokine MCP-1 by human TEC. The differential effects of 1,25-D3 on renal tubular cytokine secretion have to be considered in therapeutic dials on this hormone, e.g. in renal transplant rejection.

Calcitriol↗
PubMed2001

Absence of cytokine response to bacterial challenge in human tubuloepithelial cells.

In acute bacterial renal infections, which are most frequently caused by Escherichia coli, tubuloepithelial cells are involved with respect to bacterial adherence, invasion and cytotoxicity. In addition, cytokines expressed by tubuloepithelial cells may be relevant for the recruitment of inflammatory cells and tissue damage in bacterial interstitial nephritis. We asked which inflammatory cytokines are produced by primary human tubuloepithelial cells following in vitro exposure to E. coli and found no release of IL-6, IL-8 and TNF-alpha by tubular cells challenged by bacteria. Purified virulence factors (fimbriae, lipopolysaccharide) from E. coli were also without effects on cytokine release by tubular cells. Since lymphocytic infiltration is a characteristic feature in the chronic form of interstitial nephritis, MHC class II expression by tubular cells in response to bacterial coincubation was analyzed. Exposure to both IFN-gamma and E. coli enhanced MHC class II expression on tubuloepithelial cells. In conclusion, tubuloepithelial cells may play an active role in the local defense against bacteria, e.g. by expressing MHC class II molecules. However, in vitro inflammatory cytokines are not induced by E. coli in this cell population.

Bacterial Proteins↗
PubMed2001

Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression.

OBJECTIVE: Depression is commonly associated with frontal hypometabolic activity accompanied by hypermetabolism in certain limbic regions. It is unclear whether successful antidepressant treatments reverse these abnormalities or create new resting levels of metabolism. The aim of the present study was to assess the effects of successful paroxetine treatment on regional glucose metabolism in patients with major depression. METHOD: Positron emission tomography with [(18)F]fluorodeoxyglucose was performed on 13 male patients before and after 6 weeks of paroxetine therapy. Resting state scans were also acquired under similar conditions in 24 healthy male subjects for comparison. RESULTS: After successful paroxetine therapy, increased glucose metabolism occurred in dorsolateral, ventrolateral, and medial aspects of the prefrontal cortex (left greater than right), parietal cortex, and dorsal anterior cingulate. Areas of decreased metabolism were noted in both anterior and posterior insular regions (left) as well as right hippocampal and parahippocampal regions. In comparison to metabolism levels in a group of healthy volunteers, the increase in prefrontal metabolic activity represented a normalization of previously reduced metabolic activity, whereas the reduction in pregenual anterior cingulate activity represented a decrease from previously elevated metabolic levels. CONCLUSIONS: These results provide further support for a dysfunction in cortical-limbic circuitry in depression, which is at least partly reversed after successful paroxetine treatment.

Adult↗
PubMed2001

Multiple aseptic pulmonary nodules with central necrosis in association with pyoderma gangrenosum.

Pulmonary manifestations of pyoderma gangrenosum are relatively rare. We report the case of a 45-year-old patient with multiple pulmonary nodules with central necrosis as assessed by CT scan. The patient had a 4-year history of pyoderma gangrenosum with only minor skin manifestations. A CT-guided, fine-needle biopsy of the lung revealed a nonspecific, inflammatory, aseptic necrotic process, which was comparable to the skin biopsy of one pyoderma lesion. Following the initiation of oral prednisolone therapy, a rapid resolution of the pulmonary nodules occurred. We conclude that pulmonary nodules represent a rare pulmonary manifestation of pyoderma gangrenosum.

Female↗
PubMed2001

Diagnosis of pulmonary arterial hypertension and pulmonary embolism with magnetic resonance angiography.

BACKGROUND: Pulmonary magnetic resonance angiography (PMRA) has been proven to be accurate for the diagnosis of suspected acute or chronic pulmonary embolism (PE). Only limited data exist on the reliability of PMRA for the diagnosis of acute and chronic pulmonary artery hypertension (PAH). The aim of this study was to determine the accuracy of PMRA in the differentiation between patients suffering from PAH of varying etiologies. METHODS: Fifty patients (21 women; mean [+/- SD] age, 52 +/- 16 years) were examined with gadolinium-enhanced PMRA for the evaluation of pulmonary artery (PA) disease. The diagnosis of PAH (ie, systolic PA pressure of > 35 mm Hg) was determined by Doppler echocardiography. The criteria for the diagnosis of chronic PAH by PMRA were dilated central PAs (diameter > 28 mm) and abnormal proximal-to-distal tapering of the PAs. The diagnostic criterion for acute and chronic PE was the presence of an intravascular filling defect. RESULTS: Chronic PAH was present in 18 patients, which was correctly identified by PMRA in 16 patients (sensitivity, 89%). All patients without PAH had normal findings on PMRA (specificity, 100%). Only 1 of 18 patients with normal findings on PMRA showed moderate chronic PAH (negative predictive value, 94%). PAH due to acute/subacute pulmonary thromboembolism (15 patients) was identified in all patients (sensitivity, 100%). Acute PAH was differentiated from chronic PAH in all cases by the detection of intravascular filling defects and the lack of abnormal proximal-to-distal tapering of PAs. CONCLUSIONS: PMRA is a promising noninvasive imaging modality for the identification of patients with acute or chronic PAH. This technique should be considered a sensitive and highly specific screening tool for suspected chronic PAH.

Acute Disease↗