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Biomarkers and bacterial pneumonia risk in patients with treated HIV infection: a case-control study
(2013)
Bjerk, Sonja M. ; Baker, Jason V. ; Emery, Sean ; Neuhaus, Jacqueline ; Angus, Brian ; Gordin, Fred M. ; Pett, Sarah L. ; Stephan, Christoph ; Kunisaki, Ken M.
Background: Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist.
Methods: We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1:1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls.
Results: Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm3. Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 µg/mL in cases vs. 1.93 µg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively).
Conclusions: In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk.
Frisch, Stefan ; Dukart, Jürgen ; Vogt, Barbara ; Horstmann, Annette ; Becker, Georg ; Villringer, Arno ; Barthel, Henryk ; Sabri, Osama ; Müller, Karsten ; Schroeter, Matthias
Introduction: We aimed at dissociating the neural correlates of memory disorders in Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD).
Methods: We included patients with AD (n = 19, 11 female, mean age 61 years) and FTLD (n = 11, 5 female, mean age 61 years) in early stages of their diseases. Memory performance was assessed by means of verbal and visual memory subtests from the Wechsler Memory Scale (WMS-R), including forgetting rates. Brain glucose utilization was measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and brain atrophy by voxel-based morphometry (VBM) of T1-weighted magnetic resonance imaging (MRI) scans. Using a whole brain approach, correlations between test performance and imaging data were computed separately in each dementia group, including a group of control subjects (n = 13, 6 female, mean age 54 years) in both analyses. The three groups did not differ with respect to education and gender.
Results: Patients in both dementia groups generally performed worse than controls, but AD and FTLD patients did not differ from each other in any of the test parameters. However, memory performance was associated with different brain regions in the patient groups, with respect to both hypometabolism and atrophy: Whereas in AD patients test performance was mainly correlated with changes in the parieto-mesial cortex, performance in FTLD patients was correlated with changes in frontal cortical as well as subcortical regions. There were practically no overlapping regions associated with memory disorders in AD and FTLD as revealed by a conjunction analysis.
Conclusion: Memory test performance may not distinguish between both dementia syndromes. In clinical practice, this may lead to misdiagnosis of FTLD patients with poor memory performance. Nevertheless, memory problems are associated with almost completely different neural correlates in both dementia syndromes. Obviously, memory functions are carried out by distributed networks which break down in brain degeneration.
The aim of this study was to investigate the diagnostic power of CA 549, MSA and CA 15-3 in identifying breast cancer. The study included 232 patients of which 56 were healthy, 43 had benign breast cancer and 191 with other growths. The results were obtained using a specific immunoassay and using producers' cut offs. The following sensitivity and specificity of markers were found: CA 549 (sen.: 40%/spec.: 90%), MSA (sen.: 22%/spec.: 96%), and CA 15-3 (sen.: 33%/spec.: 86%). Ideal cut offs were defined with ROC curves. A significant correlation was found between CA 549, MSA, and CA 15-3. The combination of markers does not improve the clinical usefulness to identify only breast cancer. Serum tumor markers are abnormally elevated in patients with breast cancer. CA 549, MSA, CA 15-3 are useful clinical markers, good indicators of disease extent, and may have important prognostic value. This study demonstrates the role of the tumor markers in breast cancer.
Broch, Ole ; Grünewald, Matthias Lars ; Renner, Jochen ; Meybohm, Patrick ; Schöttler, Jan ; Heß, Katharina ; Steinfath, Markus ; Bein, Berthold Helmut
Background: The ability of stroke volume variation (SVV), pulse pressure variation (PPV) and global end-diastolic volume (GEDV) for prediction of fluid responsiveness in presence of pleural effusion is unknown. The aim of the present study was to challenge the ability of SVV, PPV and GEDV to predict fluid responsiveness in a porcine model with pleural effusions.
Methods: Pigs were studied at baseline and after fluid loading with 8 ml kg−1 6% hydroxyethyl starch. After withdrawal of 8 ml kg−1 blood and induction of pleural effusion up to 50 ml kg−1 on either side, measurements at baseline and after fluid loading were repeated. Cardiac output, stroke volume, central venous pressure (CVP) and pulmonary occlusion pressure (PAOP) were obtained by pulmonary thermodilution, whereas GEDV was determined by transpulmonary thermodilution. SVV and PPV were monitored continuously by pulse contour analysis.
Results: Pleural effusion was associated with significant changes in lung compliance, peak airway pressure and stroke volume in both responders and non-responders. At baseline, SVV, PPV and GEDV reliably predicted fluid responsiveness (area under the curve 0.85 (p<0.001), 0.88 (p<0.001), 0.77 (p = 0.007). After induction of pleural effusion the ability of SVV, PPV and GEDV to predict fluid responsiveness was well preserved and also PAOP was predictive. Threshold values for SVV and PPV increased in presence of pleural effusion.
Conclusions: In this porcine model, bilateral pleural effusion did not affect the ability of SVV, PPV and GEDV to predict fluid responsiveness.
Background. The aim of this study was to show the importance of the bone marker procollagen type 1 aminoterminal propeptide (P1NP) in detecting bone metastases in women suffering from breast cancer. We furthermore investigated to what degree P1NP is correlated to the degree of bone metastases, and if P1NP is increased in patients with metastases other than bone. Patients and Methods. We analyzed 80 serum samples of women (17 premenopausal/63 postmenopausal) with breast cancer. Therefore we used a specific immunoassay “ELECSYS 2010” by Roche Diagnostics. We divided our group of patients with regard to menopausal status, sites of metastases and number of bone metastases. Results. As a result we found higher concentrations of P1NP in women with radiologically confirmed bone metastases (median: 125.75 ng/mL) in comparison to the collective without bone involvement (median: 73.61 ng/mL). However, both groups showed values above the applied cutoff values of median 27.8 ng/mL for premenopausal women and median: 37.1 ng/mL for the postmenopausal group due to the fact that all patients had cancer. Furthermore higher P1NP concentrations were found in women with more than 5 sites of bone metastases (median: 183.9 ng/mL) than in patients with only one site of bone metastases (median: 37 ng/mL). Also patients with no bone involvement but other sites of metastases showed quite high P1NP concentrations (median: 73.61 ng/mL). Conclusion. The marker of bone turnover procollagen type 1 aminoterminal propeptide can be considered as a useful tool for estimating the extent of bone involvement and for the detection of bone metastases. P1NP cannot replace conventional methods for detecting bone metastases such as radiological methods but it can help clarify unclear radiological results. This study does not take into account the change of P1NP concentration during the course of therapy.
Herzog, Elena ; Gu, Wei ; Juhnke, Hanno Dominik ; Haas, Alexander H. ; Mäntele, Werner ; Simon, Jörg ; Helms, Volkhard ; Lancaster, C. Roy D.
The E-pathway of transmembrane proton transfer has been demonstrated previously to be essential for catalysis by the diheme-containing quinol:fumarate reductase (QFR) of Wolinella succinogenes. Two constituents of this pathway, Glu-C180 and heme b(D) ring C (b(D)-C-) propionate, have been validated experimentally. Here, we identify further constituents of the E-pathway by analysis of molecular dynamics simulations. The redox state of heme groups has a crucial effect on the connectivity patterns of mobile internal water molecules that can transiently support proton transfer from the b(D)-C-propionate to Glu-C180. The short H-bonding paths formed in the reduced states can lead to high proton conduction rates and thus provide a plausible explanation for the required opening of the E-pathway in reduced QFR. We found evidence that the b(D)-C-propionate group is the previously postulated branching point connecting proton transfer to the E-pathway from the quinol-oxidation site via interactions with the heme b(D) ligand His-C44. An essential functional role of His-C44 is supported experimentally by site-directed mutagenesis resulting in its replacement with Glu. Although the H44E variant enzyme retains both heme groups, it is unable to catalyze quinol oxidation. All results obtained are relevant to the QFR enzymes from the human pathogens Campylobacter jejuni and Helicobacter pylori.
Recent psychophysical research supports the notion that horizontal information of a face is primarily important for facial identity processes. Even though this has been demonstrated to be valid for young adults, the concept of horizontal information as primary informative source has not yet been applied to older adults’ ability to correctly identify faces. In the current paper, the role different filtering methods might play in an identity processing task is examined for young and old adults, both taken from student populations. Contrary to most findings in the field of developmental face perception, only a near-significant age effect is apparent in upright and un-manipulated presentation of stimuli, whereas a bigger difference between age groups can be observed for a condition which removes all but horizontal information of a face. It is concluded that a critical feature of human face perception, the preferential processing of horizontal information, is less efficient past the age of 60 and is involved in recognition processes that undergo age-related decline usually found in the literature.
Grundmann, Florian ; Dill, Veronika ; Dowling, Andrea ; Thanwisai, Aunchalee ; Bode, Edna ; Chantratita, Narisara ; ffrench-Constant, Richard ; Bode, Helge Björn
Two new and five known oxazoles were identified from two different Pseudomonas strains in addition to the known pyrones pseudopyronine A and B. Labeling experiments confirmed their structures and gave initial evidence for a novel biosynthesis pathway of these natural oxazoles. In order to confirm their structure, they were synthesized, which also allowed tests of their bioactivity. Additionally, the bioactivities of the synthesis intermediates were also investigated revealing interesting biological activities for several compounds despite their overall simple structures.
Lustenberger, Thomas ; Meier, Christoph ; Benninger, Emanuel ; Lenzlinger, Philipp M. ; Keel, Marius Johann Baptist
BACKGROUND: Exsanguinating hemorrhage is the major cause of death in patients with pelvic ring disruption.
AIMS: The aim of this study was to document outcomes after the stabilization of pelvic ring injuries by a C-clamp and control of hemorrhage by pelvic packing. Physiological parameters were tested as prognostic factors.
SETTING AND DESIGN: This was a retrospective study at a level I trauma center. The study period was from January 1996 to December 2007.
MATERIALS AND METHODS: Fifty patients with pelvic ring disruption and hemorrhagic shock were analyzed. The pelvic rings were fixed by a C-clamp, and patients with ongoing hemorrhage underwent laparotomy and extra- and/or intra-peritoneal pelvic packing. Clinical parameters (heart rate, mean arterial pressure) and physiological parameters (lactate levels, hemoglobin, hematocrit) were documented at admission and at different time points during the initial treatment (1, 2, 3, 4, 6, 8, and 12h after admission).
RESULTS: Within 12 h of admission, 16 patients died (nonsurvivors) due to hemorrhagic shock (n=13) or head injuries (n=3). In this group, 12 patients underwent laparotomy with pelvic packing. Thirty-four patients survived the first 12 h (early survivors) after fixation by a C-clamp and additional packing in 23 patients. Four of these patients died 12.3±7.1 days later due to multiple organ failure (n=3) or severe head injury (n=1). The blood lactate level at admission was significantly higher in the group of nonsurvivors (7.2±0.8 mmol/L) compared to the early survivors (4.3±0.5 mmol/L, P<0.05). While hemoglobin values improved within the first 2 h in nonsurvivors, lactate levels continued to increase.
CONCLUSION: Pelvic packing in addition to the C-clamp fixation effectively controls severe hemorrhage in patients with pelvic ring disruption. Early sequential measurements of blood lactate levels can be used to estimate the severity of shock and the response to the shock treatment.