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Biomedical subjects

C Lutz

Publications and source records attributed to C Lutz.

At least 19 recordsLinked to original sources

Survival after reduced-intensity conditioning is not inferior to standard high-dose conditioning before allogeneic haematopoietic cell transplantation in acute leukaemias.

To assess the role of allogeneic stem cell transplantation (SCT) after reduced-intensity conditioning (RIC) in acute leukaemias, we retrospectively compared 25 patients with acute lymphoblastic leukaemia or acute myelogenous leukaemia after RIC to a historical group of 50 matched controls after high-dose conditioning. Engraftment, acute GvHD and severe infections were comparable in both groups. During the observation period, 1/25 patients (4%) after RIC and 14/50 (28%) after standard SCT died due to transplant-related causes; cumulative nonrelapse mortality (NRM) was 4% after RIC and 24% after standard SCT (P=0.029). In total, 15/25 patients (60%) relapsed after RIC and 20/50 (40%) after standard SCT; probability of disease-free survival (DFS) at 3 years was 43% after RIC and 49% after standard SCT (NS). Overall survival (OS) was 40% after RIC and 37% after standard SCT (NS). Stage of disease, cytogenetic risk profile, acute and chronic GvHD, chimerism status at day 90 and severe infections after transplantation were risk factors with significant impact on DFS and/or OS. In retrospective analysis, patients with acute leukaemias who receive RIC because of contraindications against standard SCT have a comparable outcome to standard SCT, but the higher relapse rate warrants further studies.

Acute Disease↗

Implantation of the Freehand System during initial rehabilitation using minimally invasive techniques.

STUDY DESIGN: Series of four single subjects with and without intervention design. OBJECTIVES: To describe a minimally invasive surgical technique used to implant the Freehand System during initial spinal cord injury (SCI) rehabilitation and to report rehabilitation outcomes of four recently injured adolescents using the Freehand System. SETTING: Nonprofit children's hospital specializing in orthopedic and SCI care. METHODS: Four subjects with C5 tetraplegia between 13 and 16 years of age and between 9 and 16 weeks following traumatic SCI underwent implantation of the Freehand System using minimally invasive surgical techniques. Outcomes on muscle strength, pinch force, hand function, performance of activities of daily living and satisfaction with and without the Freehand System were collected. RESULTS: Each subject was successfully implanted with the Freehand System without perioperative complications and employed the Freehand System during therapy services and ad lib on the rehabilitation floor. At the last follow-up, every subject remained a motor candidate for the Freehand System. With the Freehand System, average lateral and palmar pinch force was 1.8 and 1.6 kg respectively; average pinch force without functional electrical stimulation (FES) was 0.29 kg. With the Freehand System, three subjects improved their rate of performance on The Upper Extremity Capabilities Questionnaire. All subjects increased their level of independence on The Quadriplegia Index of Function. On the Canadian Occupational Performance Measure (COPM) with the Freehand System, average performance and satisfaction scores improved for every patient. Three of the four subjects continued to use the system at home. CONCLUSION: This case series demonstrates that the Freehand System can vastly improve hand function and performance of rehabilitation activities within days after a minimally invasive implant procedure during initial SCI rehabilitation. Satisfaction with the Freehand System beyond initial rehabilitation is evidenced by continued use at home.

Activities of Daily Living↗

Cognitive complexity and the validity of clinicians' judgments.

Efforts to explain why some neuropsychologists are more accurate than others have been unsuccessful. In the present study, the relation between the cognitive complexity of clinicians and the validity of their judgments was investigated. Forty-two neuropsychologists completed a measure of cognitive complexity. The hypothesis that neuropsychologists who are high in cognitive complexity will be more accurate than those who are low in cognitive complexity was not supported. It is not clear why cognitive complexity was not significantly related to the validity of diagnostic ratings: One explanation is that the measure of cognitive complexity used in this study was inadequate but another possibility is that neuropsychologists who are low in cognitive complexity may still be able to achieve high levels of accuracy if they attend to normative data when they interpret test results.

Adult↗

Control of early viral and bacterial distribution and disease by natural antibodies.

Natural antibodies are often dismissed from immunological analysis as "background," but they may play an important role in conferring immunity against infections. In antibody-free mice infected with various viruses or with Listeria monocytogenes, viral or bacterial titers in peripheral organs, including the kidney and brain, were 10 to 100 times greater than in antibody-competent mice (and enhanced their susceptibility to some infections), and titers in secondary lymphoid organs were 10 to 100 times lower than in antibody-competent mice. Thus, natural antibodies play a crucial role by preventing pathogen dissemination to vital organs and by improving immunogenicity through enhanced antigen-trapping in secondary lymphoid organs.

Animals↗

Control of ribosomal protein L1 synthesis in mesophilic and thermophilic archaea.

The mechanisms for the control of ribosomal protein synthesis have been characterized in detail in Eukarya and in Bacteria. In Archaea, only the regulation of the MvaL1 operon (encoding ribosomal proteins MvaL1, MvaL10, and MvaL12) of the mesophilic Methanococcus vannielii has been extensively investigated. As in Bacteria, regulation takes place at the level of translation. The regulator protein MvaL1 binds preferentially to its binding site on the 23S rRNA, and, when in excess, binds to the regulatory target site on its mRNA and thus inhibits translation of all three cistrons of the operon. The regulatory binding site on the mRNA, a structural mimic of the respective binding site on the 23S rRNA, is located within the structural gene about 30 nucleotides downstream of the ATG start codon. MvaL1 blocks a step before or at the formation of the first peptide bond of MvaL1. Here we demonstrate that a similar regulatory mechanism exists in the thermophilic M. thermolithotrophicus and M. jannaschii. The L1 gene is cotranscribed together with the L10 and L11 gene, in all genera of the Euryarchaeota branch of the Archaea studied so far. A potential regulatory L1 binding site located within the structural gene, as in Methanococcus, was found in Methanobacterium thermoautotrophicum and in Pyrococcus horikoshii. In contrast, in Archaeoglobus fulgidus a typical L1 binding site is located in the untranslated leader of the L1 gene as described for the halophilic Archaea. In Sulfolobus, a member of the Crenarchaeota, the L1 gene is part of a long transcript (encoding SecE, NusG, L11, L1, L10, L12). A previously suggested regulatory L1 target site located within the L11 structural gene could not be confirmed as an L1 binding site.

Amino Acid Sequence↗

Systemic inflammation induced by cardiopulmonary bypass: a review of pathogenesis and treatment.

The acute respiratory distress syndrome (ARDS) is a severe alteration in lung structure and function that develops secondary to a traumatic stimulus. When ARDS develops following cardiopulmonary bypass (CPB) it is know as postpump syndrome (PPS). ARDS can be caused by a single massive insult ("hit"); however, sequential minor insults ("hits") are more common clinically. The concept of multiple sequential insults causing ARDS has been termed the "two-hit" model of ARDS. The purpose of this article is to summarize our studies testing the hypothesis that PPS is caused by multiple sequential insults. To confirm our hypothesis, we developed a porcine model of "two-hit" PPS. Our model was composed of sequential benign insults, with CPB as the "first hit" and low dose of endotoxin as the "second-hit." It is our hypothesis that the mechanism of PPS is CPB-induced priming of polymorphonuclear leukocytes (PMNs) ("first-hit") with subsequent PMN activation by a second insult ("second-hit") such as endotoxin. Our model confirms this clinically relevant postulate, and we provide strategies to disrupt the inflammatory cascade leading to PPS.

Cardiopulmonary Bypass↗

IgD can largely substitute for loss of IgM function in B cells.

The mu and delta heavy chains of IgM and IgD, the first antibody isotypes expressed during bone-marrow B-cell development, are encoded by a common transcription unit. Expression of the mu chain on the surface of late pre-B cells allows their further development to immature B cells. Coexpression of the delta chain and emigration of the immature B cells to the periphery eventually leads to the development of naive mature IgM/IgD double-positive cells. Although IgM is important in driving B-cell development, the contribution of IgD is not clear. Here we investigate the function of IgD. We generated mice deficient in IgM (IgM-/- mice) by deleting the mu region in embryonic stem cells. IgM-/- mice showed normal B-cell development and maturation, with IgD replacing membrane-bound and secretory IgM. Moreover, specific B-cell responses and isotype class switches occurred during immunization or infection. In contrast to mice deficient in B cells, IgM-/- mice survived infection with vesicular stomatitis virus by developing neutralizing immunoglobulins, but they were more susceptible than wild-type controls with delayed specific immunoglobulin responses. These data lead us to conclude that IgD is largely able to substitute for IgM functions.

Animals↗

[Treatment strategies in therapy refractory angina pectoris: transmyocardial laser revascularization].

BACKGROUND: Does transmyocardial laser revascularization (TMLR) as a new surgical technique for treating patients with otherwise intractable angina pectoris improve myocardial perfusion or contractility? METHODS: Sixty-seven patients transferred for TMLR were evaluated by clinical evaluation, treadmill stress testing, echocardiography, ventriculography, and hybrid positron emission tomography preoperatively and in patients treated with TMLR at 6 and 12 month follow up. Hemodynamic assessment and clinical evaluation were performed perioperatively. RESULTS: In 28/67 cases (42%) CABG, in 9/67 patients (13%) CABG in combination with TMLR (combined group), and in 30/67 patients (45%) only TMLR (sole group) were performed. Perioperative mortality in the sole group was 13%, in the combined group zero, and in the CABG group 11%. In all groups a significantly improved clinical status (p < or = 0.01) 1 week postoperatively and in TMLR groups also at 6 and 12 months was observed. In the TMLR groups treadmill tolerance (p < 0.05) improved, although function, perfusion, and metabolism did not change significantly at the 6 and 12 month follow up. CONCLUSION: TMLR significantly improves clinical status and treadmill stress tolerance, but does not change function, perfusion, and metabolism.

Aged↗

Histologic findings of transmyocardial laser channels after two hours.

Histologic examination of the human myocardium has been performed several days, weeks, and months after transmyocardial laser revascularization. We performed microscopic examinations 2 hours postoperatively. In addition to the patent channel (diameter, 1 mm) and a 1-to 2-mm rim of necrosis, a 1- to 3-mm zone of myofibrillary degeneration was found. This additional reversible injury immediately after transmyocardial laser revascularization could explain the higher mortality rate in patients with reduced left ventricular function.

Aged↗

Transmyocardial laser revascularization (TMLR) in patients with unstable angina and low ejection fraction.

OBJECTIVE: Does perioperative use of the intraaortic balloon pump (IABP) improve the postsurgical outcome of patients presenting with endstage coronary artery disease, unstable angina and low ejection fraction transferred for transmyocardial laser revascularization (TMLR)? METHODS: TMLR, as sole therapy combined with the perioperative use of an intraaortic balloon pump has been assessed in seven patients with endstage coronary artery disease, unstable angina and low ejection fraction (EF < 35%). Six out of seven patients had signs of congestive heart failure. These patients are compared with 23 patients with endstage coronary artery disease, stable angina and EF > 35%, who were treated with TMLR as sole therapy without the use of IABP. The creation of transmural channels was performed by a CO2-laser. All patients were evaluated by hybrid positron emission tomography (perfusion SPECT and viability PET) and ventriculography preoperatively. Echocardiography, clinical status and hemodynamic assessment by Swan Ganz catheter were performed perioperatively. RESULTS: The perioperative mortality of this combined procedure (TMLR and IABP) was zero. Three out of seven patients had pneumonia with complete recovery. Swan Ganz catheter examinations showed deterioration of LV-function after TMLR intraoperatively and improvement after 2 h and further after 6 h on ICU (P < 0.05). In contrast, a decrease of LV-function in sole TMLR patients with an EF > 35%) has not been observed. Patients with EF < 35% needed the IABP for 2.3 days and moderate dose catecholamines for a mean of 3.0 days. The postoperative EF and resting wall motion score index (WMSI) of all analysed LV segments (evaluated by echocardiography) did not change compared to baseline (EF 31.3+/-2.6 preop. to 32.8+/-3.2 postop.; WMSI: 1.75+/-0.14 at baseline to 1.71+/-0.17 postop.). The average Canadian Angina Class at the time of discharge decreased from 4.0+/-0 (baseline) to 2.3+/-0.5 (P < 0.05) and the NYHA-Index from 3.9+/-0.3 to 2.7+/-0.5. No patient had signs of angina pectoris, whereas two patients still had signs of congestive heart failure. CONCLUSIONS: The reported data support our concept to start IABP preoperatively in patients with reduced LV contractile reserve in order to provide cardiac support during the postoperative phase of reversible decline of LV-function induced by TMLR.

Aged↗

Transmyocardial laser-revascularization: experimental studies on prolonged acute regional ischemia.

OBJECTIVE: This experimental study in pigs was undertaken to answer the question whether TMLR after acute myocardial infarction may improve regional myocardial perfusion, left ventricular function and diminish myocardial necrosis in the area at risk. METHODS: Thirty open-chest anesthetized pigs were observed for 6 h, six pigs served as controls. In 24 pigs, occlusion of the left anterior descending artery (LAD) beyond the first diagonal branch was performed: seven pigs had LAD occlusion only (ischemia group), and 17 pigs were treated by TMLR (using a CO2-laser, energy: 40 J) prior to coronary occlusion; nine pigs received one laser channel (1 mm diameter) per cm2 (laser group 1) and eight pigs two channels per cm2 in the LAD territory (laser group 2). Regional myocardial blood flow by microspheres, function (franc starling curves), histochemical assessment (triphenyl tetrazolium chloride, TTC and histology), were performed. RESULTS: The lased pigs were less prone to ventricular fibrillation (laser group 2, 38%; laser group 1, 56%; ischemic group, 100%; P < 0.05), and showed a significant smaller area of necrosis (TTC) in the area at risk (laser group 1, 23%; laser group 2, 14%; vs. ischemia group, 31%; P < 0.01). There was no significant difference between laser-treated and ischemia hearts regarding the amount of blood flow into the infarcted LAD region and the maximal left ventricular stroke work index after 6 h (P = n.s). Regional myocardial blood flow: ischemia group, 4 +/- 5 ml/100 g/min; laser group 1, 3 +/- 10 ml/100 g/min, and laser group 2, 2 +/- 10 ml/100 g/min; maximal left ventricular stroke work index: ischemia group, 1.8 mJ/g; laser group 1, 2.1 mJ/g and laser group 2, 2.1 mJ/g. CONCLUSIONS: This model of acute regional ischemia demonstrates that CO2-laser revascularization diminish significantly the incidence of ventricular fibrillation and necrosis in the area at risk, and does not change regional myocardial perfusion and global left ventricular function. This experiment indicates that TMLR may be an alternative in treating advanced ischemic heart disease.

Animals↗

Aerosolized surfactant improves pulmonary function in endotoxin-induced lung injury.

Surfactant dysfunction is a primary pathophysiologic component in patients with adult respiratory distress syndrome (ARDS). In this study we tested the efficacy of aerosolized surfactant (Sf ) replacement in a severe lung injury model of endotoxin-induced ARDS. Twenty-one certified healthy pigs were anesthetized, surgically prepared for measurement of hemodynamic and lung function, then randomized into one of four groups: (1) control (n = 5), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 6), infused with Escherichia coli LPS (100 microgram/kg) without positive end- expiratory pressure (PEEP) and ventilated with a nonhumidified gas mixture of 50% N2O and 50% O2; (3) LPS + PEEP (n = 4), infused with LPS, placed on PEEP (7.5 cm H2O), and ventilated with a humidified gas mixture; and (4) LPS + PEEP + Sf (n = 6), infused with LPS, placed on PEEP, and ventilated with aerosolized Sf (Infasurf, ONY, Inc.). All animals were studied for 6 h. Arterial PO2 significantly decreased in both the LPS and LPS + PEEP groups (LPS + PEEP = 74 +/- 19 mm Hg; LPS = 74 +/- 19 mm Hg, p < 0.05) while venous admixture (Q S/Q T) increased in these groups (LPS + PEEP = 43.3 +/- 3.9%; LPS = 47.7 +/- 11%, p < 0.05) as compared with the control group. PEEP + Sf reduced the fall in PO2 (142 +/- 20 mm Hg) and rise in Q S/Q T (15.1 +/- 3.6%) caused by LPS. Delayed induction of PEEP (2 h following LPS) did not significantly improve any parameter over the LPS group without PEEP in this ARDS model. LPS without PEEP (3.4 +/- 0.2 cells/6,400 micrometer2) caused a marked increase in the total number of sequestered leukocytes in the pulmonary parenchyma as compared with the control group (1.3 +/- 0.1 cells/6,400 micrometer2). LPS + PEEP + Sf (2.3 +/- 0.2 cells/6,400 micrometer2) significantly decreased while LPS + PEEP significantly increased (4.0 +/- 0.2 cells/6,400 micrometer2) the total number of sequestered leukocytes as compared with the LPS without PEEP group. In summary, aerosolized surfactant replacement decreased leukocyte sequestration and improved oxygenation in our porcine model of endotoxin-induced lung injury.

Aerosols↗

Gender-specific differences in the effects of testosterone and estrogen on the development of atherosclerosis in rabbits.

The aim of the present study was to investigate whether there are gender-specific differences in the effects of testosterone and estrogen on the process of atherogenesis. Thirty-two castrated male and 32 ovariectomized female rabbits were separated into 4 study groups of 8 males and 8 females each and received postoperatively a 0.5% cholesterol diet for 12 weeks. During this period either no hormones, estradiol (1 mg/kg body wt/week), testosterone (25 mg/kg body wt/week IMM), or estrogen combined with testosterone in above dosages were administered. Computerized morphometric analysis of the intimal thickening in the proximal aortic arch showed a significant inhibitory effect of estrogen in female and of testosterone in male animals (P < .05). In the group with combined treatment, the plaque size in both sexes was smaller than in the animals of the control group (P < .05). These differences were independent of changes in plasma lipid parameters. The incorporation of 5'-bromo-2'-deoxyuridine, associated with cell proliferation, into cells of the neointima was not significantly affected by the different hormone application regimens in males. In females, the incorporation rate was significantly lowered in the estrogen treated group compared with the control group (P < .05). Due to the observed differences in the sex specific atheroprotective effects of testosterone and estrogen, these data suggest that complex hormone interactions, which are independent of changes in plasma lipids, may play an important role in the process of atherogenesis.

Animals↗

Nonspatial visual attention explained by spatial attention plus limited storage.

The use of nonspatial attentional mechanisms in search tasks was investigated by presenting observers with stimuli that contained 4-12 elements located on a circle around the fixation point. The elements differed in one of six nonspatial 'dimensions', namely orientation, contrast, scale, number of cycles, 'shape', and place in the alphabet. The target element of the search task differed from trial to trial but was always presented to the observer as a nonspatial, visual cue. This cue was displayed either before the stimulus (precue) or after the stimulus (postcue). Whereas a precue creates optimal conditions for the use of nonspatial attentional mechanisms, a postcue precludes benefits from their use. The fact that performance was better in the case of precued stimuli than in the case of postcued stimuli indicates that observers employed nonspatial attentional mechanisms. In the final analysis, however, the effect of nonspatial attention reduces to spatial attention in combination with limited storage capacity.

Attention↗

Pulmonary surfactant function following endotoxin: effects of exogenous surfactant treatment.

In a porcine model of endotoxin-induced adult respiratory distress syndrome (ARDS) we tested the hypothesis that the severity of lung injury would vary with the concentration of endotoxin and that reestablishment of normal surfactant function with exogenous surfactant would vary with the severity of lung injury. The therapeutic effects of exogenous surfactant treatment on pulmonary surfactant function have varied greatly in animal models of ARDS. This has created discrepancies in the literature that may be due in part to a difference in the severity of the pulmonary lesion. Yorkshire pigs were anesthetized, placed on a ventilator, and surgically prepared for hemodynamic and lung function measurements. Pigs received either 25 (25LPS) or 50 (50LPS) micrograms/kg of Escherichia coli lipopolysaccharide (LPS) followed by exogenous surfactant (SURF, 100 mg/kg) instillation, and were randomized into five groups: Control = sham LPS (n = 4); 25LPS (n = 6); 50LPS (n = 6); 25LPS + SURF (n = 5); and 50LPS + SURF (n = 6). Treatments were followed by histological and surfactant function evaluation. Histological evaluation showed the hallmarks of ARDS. Pulmonary surfactant function assessed by surfaced tension minimum (Ymin) was significantly (P < .05) elevated in both the 25LPS (20.2 +/- 2, dyne/cm) and 50LPS (19 +/- 3, dyne/cm) groups as compared with the Control group (10 +/- 1, dyne/cm). Exogenous surfactant reduced Ymin in the 25LPS + SURF group (9 +/- 2 dyne/cm, p < .05 vs. 25LPS) but not in the 50LPS + SURF group (20 +/- 1 dyne/cm, p < .05 vs. Control and 25LPS + SURF). Surfactant treatment was more effective in reestablishing normal surfactant function in animals subjected to a low dose of endotoxin, compared with animals receiving a higher dose.

Animals↗

Anatomical correlates of the passive properties underlying the developmental shift in the frequency map of the mammalian cochlea.

As the cochlea develops, the cells in the basal cochlea become sensitive to progressively higher frequencies. To identify features of cochlear morphology that may underlie the place code shift, measurements of infant and adult gerbil cochleas were made at both the light and electron microscopic levels. The measurements included areas of the cochlear duct, basilar membrane, and organ of Corti, height and width of the basilar membrane, thickness of the tympanic cover layer, thickness of the upper and lower basilar membrane fiber bands, and optical density of the basilar membrane. The results indicated that basilar membrane dimensions do not change as the place code shifts and that regions that code for the roughly the same frequency (e.g., approximately 11.2 kHz) at different ages can have basilar membranes of very different dimensions. In contrast, the size of the organ of Corti and the thickness of fiber bands inside the basilar membrane do change in ways consistent with the shift in the frequency map.

Acoustic Stimulation↗