Elevated levels of the acute‐phase serum amyloid are associated with heightened lung cancer risk

BACKGROUND:

The authors investigated whether early stage lung cancer could be identified by proteomic analyses of plasma.

METHODS:

For the first case‐control study, plasma samples from 52 patients with lung cancer and from a group of 51 controls were analyzed by surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry. In a second case‐control study, a classifier of 4 markers (mass‐to‐charge ratio, 11,681, 6843, 5607, and 8762) also was tested for validation on plasma from 16 consecutive patients with screen‐detected cancer versus 406 healthy individuals. The most relevant marker was identified, and an enzyme‐linked immunosorbent assay‐based analysis revealed that signal intensity was correlated with concentration.

RESULTS:

The classifier had a sensitivity of 94.23% and a specificity of 76.47% in the first study but lost predictive value in the second study. Nevertheless, the 11,681 cluster, which was identified as serum amyloid protein A (SAA), resulted in a multiple logistic regression model that indicated a strong association with lung cancer. When both studies were considered as a together, the odds ratio (OR) for an SAA intensity ≥0.5 was 10.27 (95% confidence interval [CI], 4.64‐22.74), whereas an analysis restricted to stage I cancers (TNM classification) revealed an OR of 8.45 (95% CI, 2.76‐25.83) for T1 lung cancer and 21.22 (95% CI, 5.62‐80.14) for T2 lung cancer.

CONCLUSIONS:

SAA levels were predictive of an elevated risk of lung cancer, supporting the general view that inflammation is implicated in lung cancer development. Cancer 2010. © 2010 American Cancer Society.     

Evaluation of the antigenotoxicity of polysaccharides and β-glucans from Agaricus blazei,a model study with the single cell gel electrophoresis/Hep G2 assay

The mushroom Agaricus blazei (Agaricus brasiliensis) has been drawing attention because of its medicinal properties. Among its isolated compounds, special consideration is given to β-glucans, which are cell wall polysaccharides. The aim of the present work was to determine the genotoxic and/or antigenotoxic effects of the total polysaccharides of this mushroom and β-glucans, both extracted at different stages of fruiting body maturity (immature, mature stage with immature spores and mature stage with mature spores). β-glucan genotoxicity was examined using the comet assay in the HepG2 cell line. Additionally, the protective effect of total polysaccharides and β-glucans was tested against H₂O₂, bleomycin and doxorubicin. The results demonstrated that total polysaccharides and β-glucans had no genotoxic effects. On the contrary, they protected DNA against damage caused by the three inducers used. However, total polysaccharides had limited protective effects while being ineffective against doxorubicin. Interestingly, the largest protective effect was seen with extracts from the ripest stages and in the absence of isolated β-glucan.     

Toremifene decreases type I, type II and increases type III receptors in desmoid and fibroma and inhibits TGFbeta1 binding in desmoid fibroblasts.

Tissue infiltration is different in desmoid and fibroma tumours. Both produce high levels of transforming growth factor beta1 (TGFbeta1), which is related to extracellular matrix (ECM) accumulation which in turn regulates cell function and cell migration. Interactions between collagen, proteoglycans and cell surface fibronectin are involved in the assembly and functions of the ECM. As toremifene inhibits collagen and TGFbeta1 synthesis, we tested it in normal, desmoid and fibroma fibroblasts. We will report the changes in glycosaminoglycan (GAG) and collagen synthesis, TGFbeta1 activity, fibronectin mRNA expression and TGFbeta1 receptors after toremifene treatment in normal, fibroma and desmoid fibroblasts. We evaluated GAG and collagen synthesis with (3)H-glucosamine and (3)H-proline incorporation, TGFbeta1 activity with the ELISA method, TGFbeta1 receptor affinity with (125)I-TGFbeta1 binding and total RNA with Northern blot analysis. GAG and collagen synthesis, TGFbeta1 activity and fibronectin levels were higher in fibroma and desmoid than normal fibroblasts. The increase was greater in desmoid than fibroma tumour cells. Toremifene treatment reduced GAG and collagen synthesis, TGFbeta1 activity and fibronectin levels in all cell cultures. The percentage reduction in GAG was similar in all cultures; the reduction in collagen synthesis and TGFbeta1 activity was the highest in desmoid fibroblasts. TGFbeta1 receptors were higher in fibroma and desmoid cells than controls. Toremifene reduced TGFbeta1 receptors only in desmoid fibroblasts, with no effect on the changes in type I, II, and III receptors. Our data show that toremifene modifies the ECM components that regulate cytokine activity and cell migration. The reduction in receptor number only in desmoid cells suggests that toremifene may reduce TGFbeta1's affinity for its receptors. Synthesis of a substance regulating protein kinase activity, which is directly involved in the link between TGFbeta1 and its receptors, cannot be excluded.     

Problematic resident-patient relationships

OBJECTIVES: The objectives of the study were to identify the characteristics of a problematic doctor-patient relationship from the perspective of primary care patients who are cared for by medical residents and to determine whether patients' perception of the relationship is a function of their demographic, clinical, or social attributes. DESIGN: Cross-sectional survey. SETTING: An adult primary care practice in an academic medical center. PATIENTS: One hundred fifty-one patients whose primary care physicians were senior internal medicine residents. MEASUREMENTS AND MAIN RESULTS: Patients completed a questionnaire addressing several aspects of their doctor-patient relationship, the general health perception item on the SF-12, and items on social support from the Duke Social Support and Stress Scale. By design of the study, approximately half of the patients had been identified by their physicians as being in problematic relationships (n = 74) and half as being in satisfying relationships (n = 77). Among patients in relationships described as satisfying by their resident, 10% viewed the relationship as problematic. Of the patients involved in relationships described as problematic by the resident, 23% viewed their relationship as problematic (P = .03). Patients who rated the relationship as problematic were much more likely to also report low social support compared to patients involved in relationships described as satisfying (76% vs 16%; P < .001). Compared to residents involved in relationships described as satisfying by their patients, residents in problematic relationships were more likely to be described as being less accessible and less capable of handling medical complaints (P < . 001). CONCLUSIONS: Patients were more likely to describe the doctor-patient relationship as problematic if they felt that the resident was less accessible or less capable of handling medical complaints, or if they had low self-perceived social support.     

Haemodynamics during liver transplantation in familial amyloidotic polyneuropathy: study of the intraoperative cardiocirculatory data of 50 patients.

BACKGROUND: Circulatory instability frequently complicates liver transplantation for familial amyloidotic polyneuropathy (FAP) and may be a source of surgical morbidity and mortality. OBJECTIVE: To evaluate FAP intraoperative haemodynamic data and their relation to the duration of surgery, and need for anaesthetic drugs. RBC and sympathomimetic amines. SETTING: Clinical study during a four year period. PATIENTS (mean +/- SD): Group I included 50 consecutive FAP ATTR Met 30 recipients of first transplantation. Age was 35.3 +/- 7.1 years, neurological score 34.3 +/- 13 in 100 and time elapsed from first symptom 5.0 +/- 2.7 years. Group II (control), not different concerning age and sex, included 51 patients transplanted during the same period with other pathologies. METHOD: Anaesthetic protocol, monitoring and surgical techniques were similar in both groups. Data of the two groups were compared either by the Student's t-test or Fisher's exact test. RESULTS: Low values of systemic vascular resistance index were observed in both groups, with no differences between them. Systemic arterial pressures were usually lower in group I, because cardiac index and heart rate were also significantly lower, although within normal values. However, in group I, isoflurane (a vasodilator anaesthetic) was used during less time (p < 0.05) and in lower concentrations (p < 0.01) and phenylephrine was necessary in 26% of patients vs 0 patients in group II (p < 0.001). CONCLUSION: FAP patients presented a different intraoperative behaviour when compared to other patients submitted to liver transplantation. From a clinical point of view, the authors stress: 1--As a result of autonomic dysfunction, the administration of anaesthetic drugs to FAP patients always presents the risk of producing significant hypotension; even the use of ketamine does not prevent hypotension; 2--Safety is ensured by beat-to-beat surveillance of arterial pressures and the capacity to act immediately to support circulation; 3--These patients seem to be very sensitive to decreases in the pre-load; 4--Hypotension is also frequent with an adequate pre-load, usually as the result of low SVR; an infusion of a vasoconstrictor drug emerges as the most frequent treatment requested and our experience supports it as an effective one.     

Stable isotope analysis for green coffee bean: A possible method for geographic origin discrimination

Isotope ratio mass spectrometry (IRMS) and elemental analysis (EA) were applied in order to achieve geographic origin discrimination between 68 green coffee bean samples from 20 different geographic origins distributed over Central America, Pacific, South America, Africa, Asia and Oceania. Multivariate analysis of isotopic composition of the bean (δ¹³C VPDB, δ¹⁵N VAIR, δ¹⁸O VSMOW) and elemental composition (carbon and nitrogen percentage) allowed some discrimination of the geographic origin of some of the coffees included in this study. The observed differences on stable isotopic and elemental composition were mainly explained by altitude and precipitation values associated with the different geographic locations.     

Ultrastructural characterization of tooth–biomaterial interfaces prepared with broad and focused ion beams

Current available techniques for transmission electron microscopy (TEM) of tooth–biomaterial interfaces are mostly ineffective for brittle phases and impair integrated chemical and morphological characterization.ObjectivesThe aims of this study were (1) to determine the applicability of new focused ion beam (FIB) and broad ion beam (BIB) techniques for TEM preparation of tooth–biomaterial interfaces; (2) to characterize the interfacial interaction with enamel and dentin of a conventional glass-ionomer (Chemfil Superior, DeTrey Dentsply, Germany), a 2-step self-etch (Clearfil SE, Kuraray, Japan) and a 3-step etch-and-rinse (OptiBond FL, Kerr, USA) adhesives; and (3) to characterize clinically relevant interfaces obtained from actual Class-I cavities.MethodsAfter bonding to freshly extracted human third molars, non-demineralized and non-stained sections were obtained using the FIB/BIB techniques and examined under TEM.ResultsThe main structures generally disclosed in conventional ultramicrotomy samples were recognized in FIB/BIB-based ones. There were not any major differences between FIB and BIB concerning the resulting ultrastructural morphology. FIB/BIB-sections enabled to clearly resolve sub-micron hydroxyapatite crystals on top of hard tissues and the interface between matrix and filler in all materials, even at nano-scale. Some investigated interfaces disclosed areas with a distinct “fog” or “melted look”, which is probably an artifact due to surface damage caused by the high-energy beam. Interfaces with enamel clearly disclosed the distinct “keyhole” shape of enamel rods sectioned at 90°, delimited by a thin electron-lucent layer of inter-rod enamel. At regions where enamel crystals ran parallel with the interface, we observed a lack of interaction and some de-bonding along with interfacial void formation.SignificanceThe FIB/BIB methods are viable and reliable alternatives to conventional ultramicrotomy for preparation of thin sections of brittle and thus difficult to cut biomaterial–hard tissue interfaces. They disclose additional ultrastructural information about both substrates and are more suitable for advanced analytic procedures.     

From inclusion to independence – Training consumers to review research

Health and medical research invariably impacts on the lives of everyday people. Organisations in the developed world are increasingly involving the public in health research projects, and research governance structures and processes. The form the involvement takes varies, as does the level of involvement, from individuals, to groups, to the wider community. Lay community members can be trained to independently review health and medical research, and wider societal involvement in funding decisions, can be effectively fostered. The theoretical foundation, design and development of a task based consumer-training program, including a number of enabling factors to support the success of such training are presented. This work is likely to be of value to those planning to train consumers in technical or complex areas.     

Molecular medicine in ophthalmic care

BackgroundLipofuscin is the most consistent and phylogenically constant morphologic marker of cellular aging. Autofluorescence of the A2E fluorophore within retinal pigment epithelial (RPE) lipofuscin affords the opportunity for noninvasive evaluation of age- and disease-related pathophysiological changes in the human retina. It is being used in National Eye Institute/Age-Related Eye Disease Study II to evaluate age-related macular degeneration (AMD) geographic atrophy expansion. Experiments show lipofuscin can be reversed in cell culture and animal models in heart, brain, spinal cord, and retinal tissues, using an array of antioxidants and iron chelators.MethodsAn 80-year-old man with a gastric resection presented with complaints of unremitting night driving difficulty despite treatment with lutein and omega III fatty acids. Notable parafoveal deposition of retinal lipofuscin by 50° fundus auto-fluorescence (580 nm excitation/660 barrier filters) and concurrent abnormalities in non-Snellen measures of visual function–Contrast Sensitivity Function, 6.5° large field tritan threshold, 10° threshold visual fields, and deficits in the National Institutes of Health/National Eye Institute Visual Function Questionnaire (VFQ) 25 subjective night driving/mental health subscale questionnaire were obtained. The patient was placed on an over-the-counter daily oral polyphenolic mixture containing resveratrol and re-evaluated 5 months later.ResultsThe data reveal improvements in all measures of visual function, subjective improvement in vision and mental functioning on the VFQ 25, and visible clearing of RPE lipofuscin.ConclusionTo our knowledge, we believe this to be the first reported human clinical case of lipofuscin reversal in the human eye correlated with measured clinical and subjective improvement in visual and mental function after nutraceutical intervention.