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Klaus Geiger

Publications and source records attributed to Klaus Geiger.

6 recordsLinked to original sources

Side-population cells from different precursor compartments.

The rapid efflux of the fluorescent DNA-binding dye Hoechst 33342 identifies a rare, so-called side population (SP), which rapidly expels the dye, can reconstitute the bone marrow (BM) of lethally irradiated mice, and has proven negative for most lineage markers including CD34. Because SP cells from human cell sources, such as mobilized peripheral blood [apheresis products (AP)], cord blood (CB), or BM have not been extensively characterized to date, we sought to analyze SP cells from various cell sources. We detected murine SP cells with a median frequency of 0.04% (n = 23) and a 52-fold colony-forming units (CFU) increase compared to unsorted cells (p = 0.028). The median frequency of human SP cells was 0.02% (n = 90), with highest numbers in donor AP, and lower in CB and BM. Human SP cells were mostly CD34(-) and lineage marker-negative. These showed no enrichment in CFU before expansion; however, they displayed a CFU increase after 5-7 days of cytokine-supported suspension culture (10.7-fold at day 5, 7.2-fold at day 7; n = 17) that was significant compared to both input (day 0) SP and to non-SP cells before and after expansion (p < 0.05). SP cells demonstrated a significant long-term culture-initiating cell (LTC-IC) increase of 167-fold (n = 17) as compared to non-SP cells (p = 0.002), with the highest numbers from AP specimens. We conclude that human primitive hematopoietic cells can be isolated via Hoechst staining and that SP cells of various human sources show substantial differences and represent a rare CD34(-) population with stem cell potential.

Animals↗

Intratidal compliance-volume curve as an alternative basis to adjust positive end-expiratory pressure: a study in isolated perfused rabbit lungs.

OBJECTIVE: Repeated collapse and reopening of alveoli have been shown to aggravate lung injury, which could be prevented by positive end-expiratory pressure (PEEP). Yet, how to adjust optimum PEEP is a matter of debate. We suggest a new strategy to adjust PEEP, which is based on the analysis of the intratidal compliance-volume curve. This approach was compared with a strategy based on the static pressure-volume curve. Furthermore, two other ventilator settings were investigated. One served as a negative control likely to provoke atelectasis, and the other was expected to induce overdistension. DESIGN: Prospective, randomized block design. SETTING: Laboratory. SUBJECTS: Isolated, perfused, and ventilated rabbit lungs. INTERVENTIONS: Tidal volumes of 8 mL/kg of body weight were used throughout. After stabilization, the lungs were randomized to one of four protocols (lasting 120 mins; n = 6 per group). Group 1 was ventilated at zero end-expiratory pressure. In group 2, PEEP was set above the lower inflection point of the static pressure-volume curve. In group 3, adjustment of PEEP was based on the intratidal compliance-volume curve, as determined by the slice method. In group 4, increasing PEEP levels ensured a plateau airway pressure of 20-25 cm H2O likely to provoke overdistension. MEASUREMENTS AND MAIN RESULTS: The ventilation/perfusion (VA/Q) distribution was analyzed by the multiple inert gas elimination technique. Alveolar derecruitment was indicated by shunt and low VA/Q areas as observed in group 1. In groups 2 and 3, VA/Q data initially indicated full recruitment. In contrast to group 3, shunt increased in group 2 near completion of the experiments. Group 4 showed complete recruitment, but the VA/Q distribution included high VA/Q areas. CONCLUSIONS: The intratidal compliance-volume curve represents a rational basis for adjusting PEEP in the isolated lung model. Because this strategy does not require invasive measures and facilitates continuous assessment of ventilator settings, it may be of clinical interest.

Animals↗

Different strategies to keep the lung open: a study in isolated perfused rabbit lungs.

OBJECTIVE: Atelectatic alveoli can be recruited or kept open either by sustained inflation maneuvers or by positive end-expiratory pressure (PEEP). Little is known about potential interactions between both approaches. Especially, it is not known whether the recruiting effect of sustained inflation maneuvers is maintained in combination with a low PEEP, as suggested recently. In an attempt to answer this question, we combined sustained inflation maneuvers with either high or low PEEP. Both approaches were compared with a strategy likely to result in alveolar atelectasis and with another ensuring adequate alveolar recruitment by adjustment of PEEP alone. DESIGN: Randomized block design. SETTING: Laboratory. SUBJECTS: Isolated perfused rabbit lungs (n = 28). INTERVENTIONS: The lungs were ventilated with a tidal volume of 8 mL/kg. After stabilization, the lungs were randomized to one of four ventilatory strategies, which then were followed for 120 mins: a) PEEP 1 cm H2O (PEEP1, negative control); b) PEEP 1 cm H2O and 30 sec-sustained inflations (20 cm H2O) every 30 mins (SI-1); c) PEEP 3 cm H2O combined with sustained inflations (SI-3); and d) PEEP repeatedly adjusted following a previously established strategy ensuring full alveolar recruitment (DYN, positive control). MEASUREMENTS AND MAIN RESULTS: Distribution of ventilation and perfusion (Va/Q distribution) was analyzed by the multiple inert gas elimination technique. Volume-dependent compliance within the tidal volume was determined by using the slice method. Shunt and Va/Q mismatch significantly differed between SI-1 and SI-3, indicating full alveolar recruitment only in the latter. Data of SI-1 did not differ substantially from those of PEEP1, and data obtained in SI-3 were similar to those of DYN. CONCLUSIONS: First, enduring alveolar recruitment by sustained inflation maneuvers is only possible when the alveoli are stabilized thereafter by sufficient PEEP. Second, a ventilation strategy that uses repeated sustained inflations on a comparably high PEEP may not be superior to adequate adjustment of PEEP alone.

Animals↗

Breath markers and soluble lipid peroxidation markers in critically ill patients.

Free radical-mediated inflammatory processes account for a great portion of morbidity and mortality in critically ill patients. The purpose of this study was to determine two plasma peroxidation markers and three volatile markers related to lipid peroxidation, metabolic activity and cholesterol metabolism, and to explore relationships between the different markers and patients' clinical status. Substances were analyzed in whole blood and in exhaled air in patients with head injury, acute respiratory distress syndrome (ARDS) and in those being at risk of developing ARDS. These results were compared with the baseline measurements in healthy individuals. Additionally, patients were assessed according to their inflammatory status. Concentrations of malondialdehyde and thiobarbituric acid-reactive substances in plasma as well as pentane concentrations in breath increased with increasing inflammatory status. Although these compounds are generated through peroxidation of fatty acids, concentrations of these markers were significantly different in patient groups. Isoprene concentrations were lowest in the ARDS group. Acetone concentrations were not different between patient groups. We conclude that for the assessment of lipid peroxidation and other inflammatory reactions a set of parameters has to be defined. More detailed insights into inflammatory processes can be obtained when the volatile markers and the serum markers are considered together.

Acetone↗

Detection of cross-transmission of multiresistant Gram-negative bacilli and Staphylococcus aureus in adult intensive care units by routine typing of clinical isolates.

OBJECTIVE: To determine the potential of laboratory services in identifying cross-transmission of multiresistant Gram-negative bacilli (MR GNB) and Staphylococcus aureus in adult intensive care units by routine typing of clinical isolates. METHODS: Over a 12-month period, isolates with indistinguishable PCR fingerprints were traced back to the source patients and their epidemiologic relationships were investigated. Possible episodes of cross-transmission were ascertained, and the validity of antibiograms in identifying the same cluster assessed. RESULTS: Of 3503 specimens received by the microbiological laboratory during 5372 patient days, 1295 cultures showed bacterial growth. Of these, 132 were primary isolates of MR GNB and 92 were primary isolates of S. aureus. Thirty-two MR GNB isolates (24%) shared fingerprints with one or more other isolates. Indistinguishable isolates from epidemiologically related patients suggested 17 episodes of cross-transmission. The positive and negative predictive values of antibiogram-based identification of these episodes were 19% and 72% respectively. S aureus displayed limited genetic diversity. The two most frequent genotypes contained 19 and 16 isolates, of which the majority appeared to be epidemiologically unrelated. CONCLUSIONS: Endemic transmission of MR GNB occurs mainly between two patients and remains unrecognized by conventional laboratory investigation. Rapid genetic typing methods identify patients involved in cross-transmission and give an insight into the population dynamics of MR GNB on adult intensive care units.

Journal Article↗