Biomedical subjects

Christian Müller

Publications and source records attributed to Christian Müller.

At least 55 records · Page 3Linked to original sources

PubMed2005

Predictive value of intact parathyroid hormone measurement during surgery for renal hyperparathyroidism.

BACKGROUND AND AIMS: In contrast to that in patients with primary hyperparathyroidism, the value of intraoperative intact parathyroid hormone (iPTH) measurement is still unclear in patients with renal hyperparathyroidism and was, therefore, evaluated in a large cohort of patients. PATIENTS: Intraoperative iPTH measurement was performed in 153 patients with renal hyperparathyroidism (129 with terminal renal failure and 24 with functioning kidney graft). Subtotal and total parathyroidectomy were performed in 123 and 13 patients, respectively, during initial surgery. In patients with recurrent disease (17), the respective hyperfunctioning tissue was removed. Intraoperative blood samples were obtained by puncture of the internal jugular vein before preparation of the parathyroids (PTH0) and 15 min after parathyroidectomy (PTH15). iPTH was measured with the Elecsys 2010 system. Postoperative iPTH levels (PTH(post)) were determined at postoperative days 1 to 3 and at week 2. Patients were arbitrarily divided in four groups according to the postoperative iPTH values: 0-25 pg/ml (group 1), 26-65 pg/ml (group 2), 66-150 pg/ml (group 3) and more than 150 pg/ml (group 4). RESULTS: The mean PTH0 value was 869+/-57 pg/ml, which decreased to 167+/-15 pg/ml at PTH15. The mean relative PTH15 value was 21.6+/-1.7%. Postoperatively, iPTH decreased to 42+/-9 pg/ml. The postoperative iPTH value of the 129 patients with terminal renal failure was 25 pg/ml or less in 99 patients, 26-65 pg/ml in 11 patients, 66-150 pg/ml in eight patients and higher than 150 pg/ml in 11 patients. Two successive criteria of iPTH decrease were used: first, a PTH15 of < or =150 pg/ml or, second, a relative PTH15 of < or =30% less was used. Fifteen patients did not fulfil both criteria. In 13 of them (86.7%) iPTH(post) was higher than 65 pg (true failure to decline). Of 114 patients who fulfilled the criteria, 108 (94.7%) had normal postoperative iPTH values (true decline). Absolute PTH15 values of less than 150 pg/ml predicted normal postoperative iPTH levels in 77 of 78 patients. CONCLUSION: A PTH15 value of 150 pg/ml or less predicts operative success in patients with renal failure in 98.7% of cases, independently of the relative decay. In contrast, if the relative PTH15 is higher than 30%, high postoperative PTH values are predicted with a probability of 86.7%. Although there remain some borderline cases, intraoperative iPTH measurement is accurate and also can be useful in patients with renal hyperparathyroidism.

Chronic Kidney Disease-Mineral and Bone Disorder↗

PubMed2005

High-resolution colocalization of single molecules within the resolution gap of far-field microscopy.

To obtain detailed information about the three-dimensional (3D) organization of small biomolecular assemblies with a size of less than 100 nanometers, advanced techniques are required that enable the determination of absolute 3D positions and distances between individual fluorophores well below the resolution limit of conventional light microscopy. We show how spectrally resolved fluorescence lifetime imaging microscopy (SFLIM) can provide significant contributions and allow us to determine distances between conventional individual fluorophores (Bodipy 630/650 and Cy5.5) that are less than 20 nm apart. We take advantage of fluorescent dyes (here Cy5.5 and Bodipy 630/650) that can be efficiently excited by a single pulsed diode laser emitting at 635 nm but differ in their fluorescence lifetime and emission maxima. The potential of the method for ultrahigh colocalization studies is demonstrated by measuring the end-to-end distance between single fluorophores separated by double-stranded DNA of various lengths. Combining SFLIM with polarization-modulated excitation allows us to obtain, simultaneously, information about the relative orientation of fluorophores. Furthermore, we show that the environment-dependent photophysics of conventional fluorophores, that is, photostability, blinking pattern, and the tendency to enter irreversible nonfluorescent states, sets certain limitations to their in vitro and in vivo applications.

Algorithms↗

PubMed2005

Triple knockouts reveal gene interactions affecting fertility of male mice.

Triple knockout mice were used to investigate the interactions of five genes that were expressed in meiotic and haploid spermatogenic cells in mice, transition protein 2 (Tnp2), proacrosin (Acr), histone H1.1 (H1.1), histone H1t (H1t), and sperm mitochondria-associated cysteine-rich protein (Smcp). TNP2 functions in the replacement of histones and the initial condensation of the spermatid nucleus. The linker histone subtypes H1.1 and H1t are expressed at high levels in meiotic and early haploid cells. ACR, a protease that is stored as a proenzyme in the acrosome, is activated during the acrosome reaction and functions in binding of sperm to the zona pellucida. SMCP is a structural protein in the outer membranes of sperm mitochondria that functions in motility. Previous work demonstrates that homozygous knockout mice lacking each of these proteins individually exhibit no defect in fertility on mixed genetic backgrounds. In contrast, the present study demonstrates that five triple knockout lines, Acr/H1.1/Smcp, Acr/Tnp2/Smcp, Tnp2/H1.1/Smcp, Acr/H1t/Smcp, Tnp2/H1t/Smcp, exhibit drastic reductions in fertility on mixed genetic backgrounds. Analysis of fertility parameters reveal that the decreased fertility is due to line-dependent defects in sperm motility in vitro correlated with reduced migration in the female reproductive tract, and decreased fertilization due to defects in adhesion of sperm to the zona pellucida, the membrane surrounding the egg. It was also found that triple knockout males, that are hemizygous for one locus and homozygous for two other loci, are as subfertile as homozygous triple knockout males, a phenomenon known as haploinsufficiency. These findings demonstrate that male fertility involves synergistic interactions of genes that function in sperm motility and sperm-egg adhesion during fertilization.

Acrosome Reaction↗

PubMed2005

Estrogen-like effects of ultraviolet screen 3-(4-methylbenzylidene)-camphor (Eusolex 6300) on cell proliferation and gene induction in mammalian and amphibian cells.

We tested the ultraviolet screen 3-(4-methylbenzylidene)-camphor (4-MBC; Eusolex 6300), which has been implicated as a potential endocrine disruptor, for its potential to bind to and activate endogenous estrogen receptors (ER) and to mediate ER-dependent changes in gene transcription, in hepatocytes of the water-dwelling South African clawed frog Xenopus laevis. We were able to confirm previous findings that 4-MBC accelerates cell proliferation in estrogen-dependent human breast cancer cells (MCF-7). Results of competitive binding assays of [3H]17beta-estradiol and 4-MBC using cytosolic protein preparations from Xenopus hepatocytes indicated that 4-MBC weakly binds to the ER. 4-MBC at a concentration of 100 micromol/L is not able to completely replace estradiol from the receptor. However, when 4-MBC was tested in a gene induction assay using the relative amount of ER transcript as a marker for ER-dependent transcriptional activation, we found that micromolar concentrations of this substance produced an increase in the amount of ER mRNA that was not different from the amount of mRNA that was observed upon activation of cells with 17beta-estradiol in concentrations above 1 nmol/L. The results indicate that 4-MBC has the potential to change physiological and developmental processes mediated by ER signaling mechanisms. It may therefore be a potentially harmful substance for water-dwelling animals when present in the environment at micromolar concentrations.

Animals↗

PubMed2005

Granulomatous inflammation of salt glands in ducklings (Anas platyrhynchos) associated with intralesional Gram-negative bacteria.

The "nasal glands" occur in many bird species and are powerful sodium ion-excretory organs. In ducks, they are located in supraorbital bony recesses. Granulomatous inflammation of these glands occurs with an incidence of approximately 1% in ducklings (Anas platyrhynchos), and is not associated with specific clinical symptoms. We investigated nine glands of eight animals with granulomas by gross pathology and histopathology, and compared results of bacteriology with 20 non-lesioned nasal glands. Adenitis was characterized by multifocal to coalescent heterophilic granulomas with central necrotic heterophils, and multinucleate giant cells, lymphocytes and plasma cells. Within the centres of the granulomas, there were clusters of Gram-negative bacteria that were identified as halo-tolerant Pseudomonas aeruginosa, Proteus mirabilis and Aeromonas hydrophila. Normal glands contained exclusively various halo-tolerant Gram-positive bacteria, mostly Streptococcus sp. and Enterococcus sp. The distribution of lesions and lack of clinical symptoms were suggestive of a localized ascending infection via the secretory ductules.

Aeromonas hydrophila↗

PubMed2005

Hepatocellular carcinoma--survival and clinical characteristics in relation to various histologic molecular markers in Western patients.

BACKGROUND: Many genes participate in the regulation of cell proliferation and growth of tumor cells. Altered expression and loss of function of some of these gene products have been found in malignant tumors and correlated with progression and poor prognosis. AIMS: Our aim was to correlate the expression of various molecular histologic markers with tumor characteristics and survival time of patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Tumor tissues of 81 patients with HCC were investigated immunohistochemically for the expression of cellular proliferation markers Mib1 (Ki67) and c-erbB-2 (HER2/neu), cellcycle markers (p53, mdm2 and p21), CD81 (TAPA1), a marker shown to be associated with metastasis, and human leukocyte antigen (HLA)-DR expression, involved in immunological antigen presentation. RESULTS: p21 was expressed in a higher percentage (83.3 vs. 50%, P=0.014) in undifferentiated histological tumor grades (Edmondson Steiner G3 vs. G1/G2). HCC in patients with enlarged lymph nodes expressed HLA-DR in a higher percentage (28.6%) than tumors without lymph node enlargement (5.7%, P=0.006). Patients with distant metastases were less likely to express CD 81 (11.1%) on tumor cells than patients without distant metastases (38.3%, P=0.0335). No other correlation with clinical or tumor characteristics or molecular histologic markers investigated was found. P53 accumulating patients showed a worse survival than patients with tumors p53 non-accumulating (median 4.1 months vs. median 9.3 months, P=0.01798). Neither the expression nor the non-expression of proliferation, cell cycle, immunologic or cell adhesion markers was associated with differences in survival. However, patients with a low expression of cell cycle marker mdm2 survived significantly longer (median 9.4 months) as compared with patients with high expression (median 3.9 months). CONCLUSION: Our results suggest that p53 nuclear accumulation and mdm2 high expression are associated with poor survival in patients withHCC. Furthermore, patients with enlarged lymph nodes had HLA-DR-positive tumors more frequently and patients with distant metastases had tumors with CD81 expression less often.

Adult↗

PubMed2005

Application of adjuvant chemotherapy in colorectal cancer -- a survey in the region of Essen, Germany.

BACKGROUND: The value of adjuvant chemotherapy (AC) in colorectal carcinoma (CRC) is definitely proven and its application is clearly recommended by the German Cancer Society (GCS). The goal of this study was to investigate whether these findings and recommendations have been introduced in daily practice and whether this might depend on the specialization of the treating physicians. PATIENTS AND METHODS: Patients presenting with CRC in the department of oncology of the Kliniken Essen-Mitte between 1997 and 2002 who had started AC until the end of 2001 were evaluated. Data on AC were collected retrospectively from patients' records and prospectively by patient interviews. We investigated whether the guidelines of the GCS were followed and whether 5-fluorouracil (5-FU) was applied properly and we correlated the results with the treating institution. RESULTS: 133 patients were analyzed for correlation of their treatment with the guidelines of the GCS. In 81% the AC met these guidelines. This was significantly more frequent in oncologic institutions than in non-specialized ones (96 vs. 9%, p < 0.001). Regarding dose and infusion time chemotherapy was properly administered to 83% of the patients (109/132) treated with 5-FU. Again, correct treatment was significantly correlated with specialization of the physicians (98 vs. 9%, medical oncology vs. other, p < 0.001). CONCLUSIONS: The results of our random search in the region of Essen, Germany, lead to the hypothesis that a quality-assured chemotherapy is best provided by specialized oncologic institutions, even if the treatment has been established for years. This should be proven by a large epidemiologic study.

Antineoplastic Agents↗

PubMed2005

Role of N-terminal pro-B-type natriuretic peptide in risk stratification in patients presenting in the emergency room.

BACKGROUND: Natriuretic peptides are promising markers in diagnosing acute and chronic heart failure and assessing prognosis in these patients. Increasing routine use to unselected patients is challenged by false-positive results. The aims of this study were to assess (a) the distributions of N-terminal B-type natriuretic peptide (NT-proBNP) values in various diagnostic groups, (b) factors that influence NT-proBNP, and (c) the value of NT-proBNP in risk stratification in unselected emergency room (ER) patients. METHODS: NT-proBNP was measured in 876 unselected consecutive patients [mean (SD) age, 58 (18) years; 53% male] attending the ERs of 2 university hospitals and 1 community hospital. Diagnoses, age, sex, hemoglobin, creatinine (CREA), C-reactive protein (CRP), troponin T, and intensity of care were documented. In a subset consisting of all 417 patients at 1 center, in-hospital follow-up was completed with respect to a complicated clinical course, including intensive care treatment and death. RESULTS: NT-proBNP was significantly increased in patients with cardiac diagnoses or histories compared with patients with only pulmonary or other diagnoses. In patients with other diagnoses, NT-proBNP values increased significantly with the number of atherosclerotic risk factors (P=0.044). Age, renal function, CRP, and to a much lesser extent, hemoglobin significantly influenced NT-proBNP values. The amount of care was positively correlated with NT-proBNP (P<0.001). Classification and regression tree analysis showed a superior impact of NT-proBNP for identification of high-risk patients. CONCLUSIONS: NT-proBNP is a promising marker for identification of patients with structural heart disease in the ER and a suitable tool for risk stratification. Its use in the ER should be limited to clearly clinically defined patient groups at present to avoid a potential excess of additional diagnostic procedures in positive but asymptomatic patients.

Acute Disease↗

PubMed2005

Impact of carbon coating on the restenosis rate after stenting of atherosclerotic renal artery stenosis.

PURPOSE: To investigate the impact of carbofilm coating and low-profile rapid exchange stent devices on the restenosis rate after stent-angioplasty of atherosclerotic renal artery stenosis (RAS). METHODS: During a 2-year period (7/2002-7/2004), 143 consecutive patients with 179 primary ostial atherosclerotic RAS>or=70% diameter stenosis were treated with stents selected at the discretion of the operator. Eighteen patients (32 lesions) treated with 9 different types of stents were excluded from the analysis, leaving 125 patients (69 men; mean age 67 years, range 42 to 90) with 147 lesions who received either a Radix carbofilm-coated stent in 78 (53%) lesions (68 [54%] patients) or a Palmaz Genesis bare stainless steel stent in 69 (47%) lesions (57 [46%] patients). The target vessel diameter ranged from 5 to 7 mm. RESULTS: Baseline characteristics were similar in both groups except the mean stent diameter, which was larger in the bare stent cohort (6.4+/-0.7 versus 5.9+/-0.5 mm, p<0.001). Primary success was 100% in both groups; the initial mean diameter stenosis was reduced from 79%+/-14% and 80%+/-14% in the coated versus bare stent groups to 3+/-5% and 2+/-6%, respectively. After a mean follow-up of 22+/-5 months, the restenosis rate was 6.4% for the coated stent and 5.8% for the bare stent (p=0.87). For the entire cohort, restenosis rates varied significantly (p<0.05) according to stent diameter: 19% (5/26) for 5 mm, 4% (3/81) for 6 mm, and 2.5% (1/40) for 7 mm. In a binary logistic regression analysis including carbofilm coating, stent diameter, gender, diabetes, smoking status, and body mass index, stent diameter was the only independent predictor of restenosis (odds ratio 0.12, 95% CI 0.03 to 0.48 [p=0.003] for a 1-mm increase in vessel diameter). CONCLUSIONS: Using modern low-profile stent devices, carbofilm coating does not significantly reduce the restenosis rate compared to a bare metal stent. With contemporary stent devices, the restenosis rate has been decreasing compared to earlier reports in the literature.

Adult↗

PubMed2005

Assessment of cerebral S100B levels by proton magnetic resonance spectroscopy after lateral fluid-percussion injury in the rat.

OBJECT: After traumatic brain injury (TBI), S100B protein is released by astrocytes. Furthermore, cerebrospinal fluid (CSF) and serum S100B levels have been correlated to outcome. Given that no data exist about the temporal profile of cerebral S100B levels following TBI and their correlation to serum levels, the authors examined whether proton magnetic resonance (MR) spectroscopy is capable of measuring S100B. METHODS: Results of in vitro proton MR spectroscopy experiments (2.35-tesla magnet, 25 G/cm, point-resolved spatially localized spectroscopy) revealed an Sl00B-specific peak at 4.5 ppm and confirmed a positive correlation between different S100B concentrations (10 nM-1 microM) and the area under the curve (AUC) for the S100B peak (r = 0.991, p < 0.001). Thereafter, proton MR spectroscopy was performed in male Sprague-Dawley rats (7 X 5 X 5-mm voxel in each hemisphere, TR 3000 msec, TE 30 msec, 256 acquisitions). Exogenously increased CSF S100B levels (approximately 200 ng/ml) through the intraventricular infusion of S100B increased the AUC of the S100B peak from 0.06 +/- 0.02 to 0.44 +/- 0.06 (p < 0.05), whereas serum S100B levels remained normal. Two hours after lateral fluid-percussion injury, serum S100B levels increased to 0.61 +/- 0.09 ng/ml (p < 0.01) and rapidly returned to normal levels, whereas the AUC of the S100B peak increased to 0.19 +/- 0.04 at 2 hours postinjury and 0.41 +/- 0.07 (p < 0.05) on Day 5 postinjury. CONCLUSIONS: Proton MR spectroscopy proves a strong correlation between the AUC of the S100B peak and S100B concentrations. Following experimental TBI, serum S100B levels increased for only a very short period, whereas cerebral S100B levels were increased up to Day 5 postinjury. Given that experimental data indicate that S100B is actively released following TBI, proton MR spectroscopy may represent a new tool to identify increased cerebral S100B levels in patients after injury, thus allowing its biological function to be better understood.

Animals↗

PubMed2005

[The letters of Hermann Rorschach to his brother].

Hermann Rorschach, brilliant creator of the projective test called after him, worked from the beginning to the middle of 1914 in a sanatorium near Moscow. Recently discovered letters to his brother Paul reveal his motives for abandoning his initial plan to settle in Russia. Apparently the impossibility of scientific work was of great importance. Additional letters complement our knowledge of Rorschach's personality.

Correspondence as Topic↗

PubMed2004

Site-isolation effects in a dendritic nickel catalyst for the oligomerization of ethylene.

Dendrimers, specifically suited to construct site-isolated groups due to their well-defined hyperbranched structure, have been used as a ligand design element for the construction of nickel catalysts for ethylene oligomerization. The dendritic P,O ligand indeed suppresses the formation of inactive bis(P,O)Ni complexes in toluene, as is evident from NMR studies, and, as a consequence, outperforms the parent ligand in catalysis in this solvent. The dendritic effect observed in methanol is more subtle because both the dendritic ligand 1 and the parent 2 form bis(P,O)nickel complexes in solution according to NMR spectroscopy. Unlike the parent complex 8, the dendritic bis(P,O)Ni complex 7 derived from dendrimer ligand 1 is able to dissociate to a mono-ligated species under catalytic conditions, that is, 40 bar ethylene and 80 degrees C, which can enter the catalytic cycle. Indeed, dendritic ligand 1 gives much more active nickel catalysts for the oligomerization in methanol than does 2.

Journal Article↗

PubMed2004

Fas/FasL and perforin/granzyme pathway in acute rejection and diffuse alveolar damage after allogeneic lung transplantation-a human biopsy study.

Acute rejection and diffuse alveolar damage are major problems during the early time after transplantation. Against this background, lung biopsies after allogeneic lung transplantation were studied using immunohistochemistry. Biopsies with acute rejection, diffuse alveolar damage and morphological inconspicuous biopsies were chosen. The objectives of this study were to ascertain: (a) if and how CD4 and CD8 T cells contribute to allograft rejection and diffuse alveolar damage, (b) whether there is a correlation of the chemoattractant regulated on activation normal T cells (RANTES) with the mononuclear infiltrate and (c) whether perforin/granzyme and Fas/FasL pathways contribute to lung injury after lung transplantation. Our results show that CD4(+) and CD8(+) T cells were increased in biopsies with acute rejection and, to a minor extent, also in biopsies with diffuse alveolar damage due to reperfusion injury. RANTES expression of T cells was increased in biopsies with acute rejection. Perforin seemed to have a dual role in the alloimmune response. In one regard, it had a cytolytic function in the acute rejection process, and, in contrast, it may be responsible for downregulating both CD4- and CD8-mediated alloimmune responses. The FasL/Fas pathway is not only important for induction of apoptosis during rejection but is also a mechanism of lung injury in the development of diffuse alveolar damage.

Acute Disease↗

PubMed2004

Differential regulatory capacity of CD25+ T regulatory cells and preactivated CD25+ T regulatory cells on development, functional activation, and proliferation of Th2 cells.

CD25+ T regulatory (Treg) cells play a central role regarding the maintenance of peripheral tolerance via suppression of autoaggressive CD4+ T cells, CD8+ T cells, and Th1 cells. In this study we demonstrate that CD25+ Treg cells can also suppress the differentiation of murine conventional CD4+ T cells toward Th2 cells in a contact-dependent manner. However, the cytokine production and proliferation of established Th2 cells could not be inhibited by freshly isolated CD25+ Treg cells, whereas a strong inhibition of differentiated Th2 cells by in vitro preactivated CD25+ Treg cells could be observed. Inhibition of both conventional CD4+ T cells and Th2 cells is accompanied by a strong enhancement of the expression of FoxP3 in the suppressed T cells. Hence, our study indicates that CD25+ Treg cells have a therapeutic potential for Th2-mediated diseases and suggests a novel mechanism of suppression mediated by the transcriptional repressor FoxP3.

Animals↗

PubMed2004

Clinical efficacy, tolerability, and safety of SAM486A, a novel polyamine biosynthesis inhibitor, in patients with relapsed or refractory non-Hodgkin's lymphoma: results from a phase II multicenter study.

PURPOSE: SAM486A is a new inhibitor of S-adenosyl-methionine-decarboxylase, a key enzyme for polyamine biosynthesis. It is more potent than the first generation S-adenosyl-methionine-decarboxylase inhibitor methylglyoxal bis-guanylhydrazone. This Phase IIa study reports the findings of SAM486A monotherapy in patients with refractory or relapsed non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Forty-one previously treated patients with either diffuse large cell, follicular, or peripheral T-cell NHL were treated i.v. with 100 mg/m(2) SAM486A as a daily 1-h infusion for 5 days repeated every 3 weeks. Treatment was continued for a total of eight cycles or until disease progression. RESULTS: Two patients, both with large B-cell lymphoma, showed a complete response at cycle 3 that was maintained for >or=13 and >or=28 months. Five patients had a partial response, and 3 had stable disease at last follow-up. The overall response rate (complete response plus partial response) was 18.9% for evaluable patients (7 patients). Anemia was the primary hematological toxicity and observed in 7 (17.1%) patients. Five patients experienced grade 3/4 anemia. Four patients (9.8%) experienced grade 3/4 febrile neutropenia and grade 3/4 thrombocytopenia, respectively. Nonhematological toxicities were mild to moderate in intensity. The most frequent side effects were nausea (39%), vomiting (22%), diarrhea (19.5%), asthenia (17.1%), abdominal pain (14.6%), and flushing (9.8%). CONCLUSION: SAM486A has a promising clinical activity in patients with poor prognosis NHL and manageable safety profile. To further define the role of SAM486A, in the treatment of NHL, additional studies are warranted.

Adenosylmethionine Decarboxylase↗

PubMed2004

Human CD25+ regulatory T cells: two subsets defined by the integrins alpha 4 beta 7 or alpha 4 beta 1 confer distinct suppressive properties upon CD4+ T helper cells.

Down-regulation of autoreactive T cell responses in vivo includes cell-contact-dependent as well as contact-independent mechanisms. Infectious tolerance is a contact-dependent mechanism used by naturally occurring CD25(+) T regulatory cells (Tregs) to confer suppressive activity upon conventional CD4(+) T cells thereby generating secondary T helper suppressor cells(Th(sup)), which inhibit T cell activation via soluble mediators. Here, we describe two distinct subsets of human Tregs, characterized by expression of either the alpha(4)beta(7) integrin or the alpha(4)beta(1) integrin. Upon activation, both subsets show an enhanced expression of FoxP3, recently described as a key transcription factor of murine Tregs. In addition, both are able to convey suppressive capacity to conventional CD4(+) T cells. However, the properties of Treg subsets are rather distinct: alpha(4)beta(7) (+)Tregs induce IL-10-producing Th(sup) (Tr1-like), whereas alpha(4)beta(1) (+) Tregs induce TGF-beta-producing Th(sup) (Th3-like). Our findings reconcile conflicting results by clearly demonstrating that suppression through naturally occurring CD25(+) Tregs is primary cell-contact-dependent but is subsequently followed by cell-contact-independent T cell inhibition mediated by second-generation Tr1- and Th3-like Th(sup) via the soluble factors IL-10 and TGF-beta.

Humans↗

PubMed2004

Human factors affect the quality of cardiopulmonary resuscitation in simulated cardiac arrests.

AIM: Cardiopulmonary resuscitation is a team endeavour. There are only limited data on whether team performance during cardiopulmonary resuscitation is influenced by behavioural issues. The aim of the study was to determine whether and how human factors affect the quality of cardiopulmonary resuscitation. METHODS: 16 teams, each consisting of three health-care workers, were studied in a patient simulator. A scenario of witnessed cardiac arrest due to ventricular fibrillation was used. Ventricular fibrillation could be converted into sinus rhythm by two countershocks administered during the first 2 min or by two countershocks administered during the first 5 min provided that uninterrupted basic life support was started in under 60 s. Teams were rated to be successful if ventricular fibrillation was converted into sinus rhythm. Behavioural rating included leadership, task distribution, information transfer, and conflicts. RESULTS: Only six out of 16 teams were successful. Compared with successful teams, teams that failed exhibited significantly less leadership behaviour (P=0.033) and explicit task distribution (P=0.035). All teams shared among them sufficient theoretical knowledge to successfully treat the simulated cardiac arrest. CONCLUSIONS: In a scenario of simulated witnessed cardiac arrest almost two thirds of teams composed of qualified health-care workers failed to provide basic life support and/or defibrillation within an appropriate time window. Absence of leadership behaviour and absence of explicit task distribution were associated with poor team performance. Failure to translate theoretical knowledge into effective team activity appears to be a major problem.

Cardiopulmonary Resuscitation↗

PubMed2004

Intraventricular infusion of the neurotrophic protein S100B improves cognitive recovery after fluid percussion injury in the rat.

Elevated serum S100B levels have been shown to be a predictor of poor outcome after traumatic brain injury (TBI). Experimental data, on the other hand, demonstrate a neuroprotective and neurotrophic effect of this calcium-binding protein. The purpose of this study was to examine the role of increased S100B levels on functional outcome after TBI. Following lateral fluid percussion or sham injury in male Sprague Dawley rats (n = 56), we infused S100B (50 ng/h) or vehicle into the cerebrospinal fluid of the ipsilateral ventricle for 7 days using an osmotic mini-pump. Assessment of cognitive performance by the Morris water maze on days 30-34 after injury revealed an improved performance of injured animals after S100B infusion (p < 0.05), when compared to vehicle infusion. Blood samples for analysis of clinical markers of brain damage, S100B and neuron specific enolase, taken at 30 min, 3 h, 4 h, 2 days, or 5 days showed a typical peak 3 h after injury (p < 0.01), and higher serum levels correlated significantly with an impaired cognitive recovery (p < 0.01). The correlation of higher serum S100B levels with poor water maze performance may result from injury induced opening of the blood-brain barrier, allowing the passage of S100B into serum. Thus while higher serum levels of S100B seem to reflect the degree of blood-brain barrier opening and severity of injury, a beneficial effect of intraventricular S100B administration on long-term functional recovery after TBI has been demonstrated for the first time. The exact mechanism by which S100B exerts its neuroprotective or neurotrophic influence remains unknown and needs to be elucidated by further investigation.

Animals↗