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1.
Kumar AA Palamaner Subash Shantha G Kahan S Samson RJ Boddu ND Cheskin LJ 《PloS one》2012,7(2):e32395
Background and Aim
Intentional weight loss, primarily by improving insulin resistance, is known to decrease the need for anti-diabetic medications. In this study, we assess the magnitude of weight loss that resulted in dose reductions or discontinuation of anti-diabetic medications in overweight or obese patients with type 2 diabetes (DM) undergoing weight loss treatment.Methods
Case records of 50 overweight or obese patients with DM who successfully decreased dosage or discontinued diabetes medications after losing weight via attendance at two University-based, outpatient weight management centers were analyzed. Follow-up visits, weight reduction interventions, and decisions for dose reductions or discontinuation of medications were individualized to patient needs by the treating physician.Results
Mean starting BMI was 35 kg/m2, mean age 53.4 years, and 58% were male. All 50 used at least one anti-diabetic medication (30 metformin, 39 sulfonylureas, 31 insulin, 21 sitagliptin) to manage blood sugar. Mean duration of follow-up was 30.2 months. Mean weight loss was 10.8±4.1 kgs (11.1% of initial body weight ±4.7%). 22/50 patients (44%) discontinued anti-diabetes medications (14 sulfonylureas [36%], 7 insulin [23%], 4 sitagliptin [19%]). The mean percentage weight loss achieved at the point of successful discontinuation of medication was 11.2%±3.5% (14% for sulphonylureas, 11% for insulin, and 7.1% for sitagliptin). Mean percentage weight loss of 5.6%±2.8% (5.1% for sulphonylureas, 4.3% for insulin, and 7.1% for sitagliptin) was required for initial dose reduction. For every 5% weight loss, predicted dose reductions were sulphonylureas, 39%; insulin, 42%; and any anti-diabetic medications, 49%.Conclusion
Among overweight or obese patients with type 2 diabetes, intentional weight loss of 7–14% was typically required for full discontinuation of at least one anti-diabetic medication. Discontinuation of insulin was achieved at a mean weight reduction of 11% of initial body weight. 相似文献2.
Background
Pulmonary embolism (PE) is a common and potentially fatal disease that is still underdiagnosed. The objective of our study was to reappraise the clinical presentation of PE with emphasis on the identification of the symptoms and signs that prompt the patients to seek medical attention.Methodology/Principal Findings
We studied 800 patients with PE from two different clinical settings: 440 were recruited in Pisa (Italy) as part of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISAPED); 360 were diagnosed with and treated for PE in seven hospitals of central Tuscany, and evaluated at the Atherothrombotic Disorders Unit, Firenze (Italy), shortly after hospital discharge. We interviewed the patients directly using a standardized, self-administered questionnaire originally utilized in the PISAPED. The two samples differed significantly as regards age, proportion of outpatients, prevalence of unprovoked PE, and of active cancer. Sudden onset dyspnea was the most frequent symptom in both samples (81 and 78%), followed by chest pain (56 and 39%), fainting or syncope (26 and 22%), and hemoptysis (7 and 5%). At least one of the above symptoms was reported by 756 (94%) of 800 patients. Isolated symptoms and signs of deep vein thrombosis occurred in 3% of the cases. Only 7 (1%) of 800 patients had no symptoms before PE was diagnosed.Conclusions/Significance
Most patients with PE feature at least one of four symptoms which, in decreasing order of frequency, are sudden onset dyspnea, chest pain, fainting (or syncope), and hemoptysis. The occurrence of such symptoms, if not explained otherwise, should alert the clinicians to consider PE in differential diagnosis, and order the appropriate objective test. 相似文献3.
Aim
Glucocorticoids (GCs) take part in the direct control of cell lineage during the late phase of pancreas development when endocrine and exocrine cell differentiation occurs. However, other tissues such as the vasculature exert a critical role before that phase. This study aims to investigate the consequences of overexposure to exogenous glucocorticoids during different time-windows of gestation for the development of the fetal endocrine pancreas.Methods
Pregnant Wistar rats received dexamethasone acetate in their drinking water (1 µg/ml) during the last week or throughout gestation. Fetuses and their pancreases were analyzed at day 15 and 21 of gestation. Morphometrical analysis was performed on pancreatic sections after immunohistochemistry techniques and insulin secretion was evaluated on fetal islets collected in vitro.Results
Dexamethasone given the last week or throughout gestation reduced the beta-cell mass in 21-day-old fetuses by respectively 18% or 62%. This was accompanied by a defect in insulin secretion. The alpha-cell mass was reduced similarly. Neither islet vascularization nor beta-cell proliferation was affected when dexamethasone was administered during the last week, which was however the case when given throughout gestation. When given from the beginning of gestation, dexamethasone reduced the number of cells expressing the early marker of endocrine lineage neurogenin-3 when analyzed at 15 days of fetal age.Conclusions
GCs reduce the beta- and alpha-cell mass by different mechanisms according to the stage of development during which the treatment was applied. In fetuses exposed to glucocorticoids the last week of gestation only, beta-cell mass is reduced due to impairment of beta-cell commitment, whereas in fetuses exposed throughout gestation, islet vascularization and lower beta-cell proliferation are involved as well, amplifying the reduction of the endocrine mass. 相似文献4.
5.
Miranda C. Kramer Allard C. van der Wal Karel T. Koch Saskia Z. Rittersma Xiaofei Li Hanneke P. Ploegmakers José P. Henriques René J. van der Schaaf Jan Baan Jr Marije M. Vis Martin G. Meesterman Jan J. Piek Jan G. Tijssen Robbert J. de Winter 《PloS one》2009,4(6)
Background
Plaque disruption with superimposed thrombus is the predominant mechanism responsible for the onset of acute coronary syndromes. Studies have shown that plaque disruption and thrombotic occlusion are frequently separated in time. We established the histopathological characteristics of material aspirated during primary percutaneous coronary intervention (PCI) in a large consecutive ST-elevation myocardial infarction (STEMI) population.Methodology/Principal Findings
Thrombus aspiration during primary PCI was performed in 1,362 STEMI patients. Thrombus age was classified as fresh (<1 day), lytic (1–5 days), or organized (>5 day). Further, the presence of plaque was documented. The histopathological findings were related to the clinical, angiographic, and procedural characteristics. Material could be aspirated in 1,009 patients (74%). Components of plaque were found in 395 of these patients (39%). Fresh thrombus was found in 577 of 959 patients (60%) compared to 382 patients (40%) with lytic or organized thrombi. Distal embolization was present in 21% of patients with lytic thrombus compared to 12% and 15% of patients with fresh or organized thrombus.Conclusions/Significance
Material could be obtained in 74% of STEMI patients treated with thrombus aspiration during primary PCI. In 40% of patients thrombus age is older than 24 h, indicating that plaque disruption and thrombus formation occur significantly earlier than the onset of symptoms in many patients. 相似文献6.
7.
Objective
To examine the epidemiology of hypertension in women of reproductive age.Methods
Using NHANES from 1999–2008, we identified 5,521 women age 20–44 years old. Hypertension status was determined using blood pressure measurements and/or self-reported medication use.Results
The estimated prevalence of hypertension in women of reproductive age was 7.7% (95% confidence interval (CI): 6.9%–8.5%). The prevalence of anti-hypertensive pharmacologic therapy was 4.2% (95% CI 3.5%–4.9%). The prevalence of hypertension was relatively stable across the study period; the age and race adjusted odds of hypertension in 2007–2008 did not differ significantly from 1999–2000 (odds ratio 1.2, CI 0.8 to 1.7, p = 0.45). Significant independent risk factors associated with hypertension included older age, non-Hispanic black race (compared to non-Hispanic whites), diabetes mellitus, chronic kidney disease, and higher body mass index. The most commonly used antihypertensive medications included diuretics, angiotensin-converting enzyme inhibitors (ACE), and beta blockers.Conclusion
Hypertension occurs in about 8% of women of reproductive age. There are remarkable differences in the prevalence of hypertension between racial/ethnic groups. Obesity is a risk factor of particular importance in this population because it affects over 30% of young women in the U.S., is associated with more than 4 fold increased risk of hypertension, and is potentially modifiable. 相似文献8.
Nguyen C Bérezné A Baubet T Mestre-Stanislas C Rannou F Papelard A Morell-Dubois S Revel M Guillevin L Poiraudeau S Mouthon L;Groupe Français de Recherche sur la Sclérodermie 《PloS one》2011,6(3):e17551
Objectives
To assess the association of gender with clinical expression, health-related quality of life (HRQoL), disability, and self-reported symptoms of depression and anxiety in patients with systemic sclerosis (SSc).Methods
SSc patients fulfilling the American College of Rheumatology and/or the Leroy and Medsger criteria were assessed for clinical symptoms, disability, HRQoL, self-reported symptoms of depression and anxiety by specific measurement scales.Results
Overall, 381 SSc patients (62 males) were included. Mean age and disease duration at the time of evaluation were 55.9 (13.3) and 9.5 (7.8) years, respectively. One-hundred-and-forty-nine (40.4%) patients had diffuse cutaneous SSc (dcSSc). On bivariate analysis, differences were observed between males and females for clinical symptoms and self-reported symptoms of depression and anxiety, however without reaching statistical significance. Indeed, a trend was found for higher body mass index (BMI) (25.0 [4.1] vs 23.0 [4.5], p = 0.013), more frequent dcSSc, echocardiography systolic pulmonary artery pressure >35 mmHg and interstitial lung disease in males than females (54.8% vs 37.2%, p = 0.010; 24.2% vs 10.5%, p = 0.003; and 54.8% vs 41.2%, p = 0.048, respectively), whereas calcinosis and self-reported anxiety symptoms tended to be more frequent in females than males (36.0% vs 21.4%, p = 0.036, and 62.3% vs 43.5%, p = 0.006, respectively). On multivariate analysis, BMI, echocardiography PAP>35 mmHg, and anxiety were the variables most closely associated with gender.Conclusions
In SSc patients, male gender tends to be associated with diffuse disease and female gender with calcinosis and self-reported symptoms of anxiety. Disease-associated disability and HRQoL were similar in both groups. 相似文献9.
Aims
Type 2 diabetes is highly prevalent in the elderly population. Glucagon like Peptide-1 mimetic such as exendin-4 augments post-prandial insulin secretion. However, the potential influence of aging on the therapeutic effects of this peptide has not been well studied. In this study, we examined the glucose regulatory effects of exendin-4 in mice with different ages.Methods
We treated 3-month and 20 to 22-month old C57/DBA mice with 10 nM/kg exendin-4 for 10 days with measurements of blood glucose and body weight. We performed OGTT and ITT to evaluate the glucose response and insulin sensitivity. Islet morphology and beta cell mass were measured by immuno-staining and beta cell proliferation was evaluated by BrdU incorporation and PCNA staining. Real-time PCR and western blot were used to measure protein changes in the liver tissue after exendin-4 treatment.Results
Exendin-4 treatment improved glycemic control in both 3-month and 20 to 22-month old mice. In both groups of mice, the blood glucose lowering effect was independent of beta cell function as indicated by unchanged beta cell proliferation, insulin secretion or beta cell mass. Moreover, we found that exendin-4 treatment increased hepatic AKT and FOXO1 phosphorylation and inhibited glucose-6-phosphotase (G6P) and Phosphoenolpyruvate carboxykinase (PEPCK) expression in young mice, but this effect was attenuated in aging mice while the insulin sensitivity showed no change in the young group but significantly improved in aging mice.Conclusion
Based on these data, we conclude that the glucose lowering effect of exendin-4 in normal non-diabetic mice was not blunted by aging. We further showed that although there was slight difference in the glucose modulating mechanism of exendin-4 therapy in young and aged mice, the improved glucose control seemed uncorrelated with increased beta cell mass or insulin secretion. 相似文献10.
Birnie K Ben-Shlomo Y Holly JM Gunnell D Ebrahim S Bayer A Gallacher J Martin RM 《PloS one》2012,7(1):e30096
Objective
Insulin and the insulin-like growth factor (IGF) system regulate growth and are involved in determining muscle mass, strength and body composition. We hypothesised that IGF-I and IGF-II are associated with improved, and insulin with worse, physical performance in old age.Methods
Physical performance was measured using the get-up and go timed walk and flamingo balance test at 63–86 years. We examined prospective associations of insulin, IGF-I, IGF-II and IGFBP-3 with physical performance in the UK-based Caerphilly Prospective Study (CaPS; n = 739 men); and cross-sectional insulin, IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in the Boyd Orr cohort (n = 182 men, 223 women).Results
In confounder-adjusted models, there was some evidence in CaPS that a standard deviation (SD) increase in IGF-I was associated with 1.5% faster get-up and go test times (95% CI: −0.2%, 3.2%; p = 0.08), but little association with poor balance, 19 years later. Coefficients in Boyd Orr were in the same direction as CaPS, but consistent with chance. Higher levels of insulin were weakly associated with worse physical performance (CaPS and Boyd Orr combined: get-up and go time = 1.3% slower per SD log-transformed insulin; 95% CI: 0.0%, 2.7%; p = 0.07; OR poor balance 1.13; 95% CI; 0.98, 1.29; p = 0.08), although associations were attenuated after controlling for body mass index (BMI) and co-morbidities. In Boyd Orr, a one SD increase in IGFBP-2 was associated with 2.6% slower get-up and go times (95% CI: 0.4%, 4.8% slower; p = 0.02), but this was only seen when controlling for BMI and co-morbidities. There was no consistent evidence of associations of IGF-II, or IGFBP-3 with physical performance.Conclusions
There was some evidence that high IGF-I and low insulin levels in middle-age were associated with improved physical performance in old age, but estimates were imprecise. Larger cohorts are required to confirm or refute the findings. 相似文献11.
Balanzat AM Hertlein C Apezteguia C Bonvehi P Cámera L Gentile A Rizzo O Gómez-Carrillo M Coronado F Azziz-Baumgartner E Chávez PR Widdowson MA 《PloS one》2012,7(4):e33670
Background
The apparent high number of deaths in Argentina during the 2009 pandemic led to concern that the influenza A H1N1pdm disease was different there. We report the characteristics and risk factors for influenza A H1N1pdm fatalities.Methods
We identified laboratory-confirmed influenza A H1N1pdm fatalities occurring during June-July 2009. Physicians abstracted data on age, sex, time of onset of illness, medical history, clinical presentation at admission, laboratory, treatment, and outcomes using standardize questionnaires. We explored the characteristics of fatalities according to their age and risk group.Results
Of 332 influenza A H1N1pdm fatalities, 226 (68%) were among persons aged <50 years. Acute respiratory failure was the leading cause of death. Of all cases, 249 (75%) had at least one comorbidity as defined by Advisory Committee on Immunization Practices. Obesity was reported in 32% with data and chronic pulmonary disease in 28%. Among the 40 deaths in children aged <5 years, chronic pulmonary disease (42%) and neonatal pathologies (35%) were the most common co-morbidities. Twenty (6%) fatalities were among pregnant or postpartum women of which only 47% had diagnosed co-morbidities. Only 13% of patients received antiviral treatment within 48 hours of symptom onset. None of children aged <5 years or the pregnant women received antivirals within 48 h of symptom onset. As the pandemic progressed, the time from symptom-onset to medical care and to antiviral treatment decreased significantly among case-patients who subsequently died (p<0.001).Conclusion
Persons with co-morbidities, pregnant and who received antivirals late were over-represented among influenza A H1N1pdm deaths in Argentina, though timeliness of antiviral treatment improved during the pandemic. 相似文献12.
Objectives
Tinnitus is the perception of a sound in the absence of any physical source of it. About 5–15% of the population report hearing such a tinnitus and about 1–2% suffer from their tinnitus leading to anxiety, sleep disorders or depression. It is currently not completely understood why some people feel distressed by their tinnitus, while others don''t. Several studies indicate that the amount of tinnitus distress is associated with many factors including comorbid anxiety, comorbid depression, personality, the psychosocial situation, the amount of the related hearing loss and the loudness of the tinnitus. Furthermore, theoretical considerations suggest an impact of the age at tinnitus onset influencing tinnitus distress.Methods
Based on a sample of 755 normal hearing tinnitus patients we tested this assumption. All participants answered a questionnaire on the amount of tinnitus distress together with a large variety of clinical and demographic data.Results
Patients with an earlier onset of tinnitus suffer significantly less than patients with an onset later in life. Furthermore, patients with a later onset of tinnitus describe their course of tinnitus distress as more abrupt and distressing right from the beginning.Conclusion
We argue that a decline of compensatory brain plasticity in older age accounts for this age-dependent tinnitus decompensation. 相似文献13.
Context
Randomized controlled trails have identified online cognitive behavioral therapy as an efficacious intervention in the management of common mental health disorders.Objective
To assess the effectiveness of online CBT for different mental disorders in routine clinical practice.Design
An uncontrolled before-after study, with measurements at baseline, posttest, 6-week follow-up, and 1-year follow-up.Participants & Setting
1500 adult patients (female: 67%; mean age: 40 years) with a GP referral for psychotherapy were treated at a Dutch online mental health clinic for symptoms of depression (n = 413), panic disorder (n = 139), posttraumatic stress (n = 478), or burnout (n = 470).Interventions
Manualized, web-based, therapist-assisted CBT, of which the efficacy was previously demonstrated in a series of controlled trials. Standardized duration of treatment varied from 5 weeks (online CBT for Posttraumatic stress) to 16 weeks (online CBT for Depression).Main Outcome Measures
Validated self-report questionnaires of specific and general psychopathology, including the Beck Depression Inventory, the Impact of Event Scale, the Panic Disorder Severity Scale-Self Report, the Oldenburg Burnout Inventory, and the Depression Anxiety Stress Scales.Results
Treatment adherence was 71% (n = 1071). Study attrition was 21% at posttest, 33% at 6-week FU and 65% at 1-year FU. Mixed-model repeated measures regression identified large short-term reductions in all measures of primary symptoms (d = 1.9±0.2 to d = 1.2±0.2; P<.001), which sustained up to one year after treatment. At posttest, rates of reliable improvement and recovery were 71% and 52% in the completer sample (full sample: 55%/40%). Patient satisfaction was high.Conclusions
Results suggest that online therapist-assisted CBT may be as effective in routine practice as it is in clinical trials. Although pre-treatment withdrawal and long-term outcomes require further study, results warrant continued implementation of online CBT. 相似文献14.
Yang SG Cao B Liang LR Li XL Xiao YH Cao ZX Jia HY Yu HJ Xu Z Gu L Yang YD Chen Y Du WB Yan XX Liang ZA Zhang W Zhang CL Chen W Guo CP Jiang XL Yang M Deng GM Yu KJ Hu K Zou Q Li LJ Wang C;National Influenza A Pandemic 《PloS one》2012,7(1):e29652
Background
There is limited data on the clinical outcome of patients with pandemic H1N1 (pH1N1) pneumonia who received oseltamivir treatment, especially when the treatment was administered more than 48 hours after symptom onset.Methods
During the pandemic in 2009, a cohort of pH1N1 influenza pneumonia was built in China, and their clinical information was collected systematically, and analyzed with Cox models.Results
920 adults and 541 children with pneumonia who didn''t receive corticosteroids were analyzed. In-hospital mortality was higher in adults who did not receive antiviral therapy (18.2%) than those with who received oseltamivir ≤ 2days (2.9%), between 2–5 days (4.6%) and >5 days after illness onset (4.9%), p<0.01. A similar trend was observed in pediatric patients. Cox regression showed that at 60 days after symptoms onset, 11 patients (10.8%) who did not receive antivirals died versus 4 (1.8%), 18 (3.3%), and 23 (3.7%) patients whose oseltamivir treatment was started ≤ 2days, between 2–5days, and >5 days, respectively. For males patients, aged ≥ 14 years and baseline PaO2/FiO2<200, oseltamivir administration reduced the mortality risk by 92.1%, 88% and 83.5%, respectively. Higher doses of oseltamivir (>3.8 mg/kg/d) did not improve clinical outcome (mortality, higher dose 2.5% vs standard dose 2.8%, p>0.05).Conclusions
Antiviral therapy might reduce mortality of patients with pH1N1 pneumonia, even when initiated more than 48 hours after onset of illness. Greater protective effects might be in males, patients aged 14–60 years, and patients with PaO2/FiO2<200. 相似文献15.
Background
Dizziness and vertigo symptoms are commonly seen in emergency room (ER). However, these patients are often discharged without a definite diagnosis. Conflicting data regarding the vascular event risk among the dizziness or vertigo patients have been reported. This study aims to determine the risk of developing stroke or cardiovascular events in ER patients discharged home with a diagnosis of dizziness or vertigo.Methodology
A total of 25,757 subjects with at least one ER visit in 2004 were identified. Of those, 1,118 patients were discharged home with a diagnosis of vertigo or dizziness. A Cox proportional hazard model was performed to compare the three-year vascular event-free survival rates between the dizziness/vertigo patients and those without dizziness/vertigo after adjusting for confounding and risk factors.Results
We identified 52 (4.7%) vascular events in patients with dizziness/vertigo and 454 (1.8%) vascular events in patients without dizziness/vertigo. ER patients discharged home with a diagnosis of vertigo or dizziness had 2-fold (95% confidence interval [CI], 1.35–2.96; p<0.001) higher risk of stroke or cardiovascular events after adjusting for patient characteristics, co-morbidities, urbanization level of residence, individual socio-economic status, and initially taking medications after the onset of dizziness or vertigo during the first year.Conclusions
ER patients discharged home with a diagnosis of dizziness or vertigo were at a increased risk of developing subsequent vascular events than those without dizziness/vertigo after the onset of dizziness or vertigo. Further studies are warranted for developing better diagnostic and follow-up strategies in increased risk patients. 相似文献16.
Wojcicki JM Holbrook K Lustig RH Epel E Caughey AB Muñoz RF Shiboski SC Heyman MB 《PloS one》2011,6(2):e16737
Background
Latino children are at increased risk for mirconutrient deficiencies and problems of overweight and obesity. Exposures in pregnancy and early postpartum may impact future growth trajectories.Objectives
To evaluate the relationship between prenatal and postnatal maternal depressive symptoms experienced in pregnancy and infant growth from birth to 2 years of age in a cohort of Latino infants.Methods
We recruited pregnant Latina mothers at two San Francisco hospitals and followed their healthy infants to 24 months of age. At 6, 12 and 24 months of age, infants were weighed and measured. Maternal depressive symptoms were assessed prenatally and at 4-6 weeks postpartum. Women who had high depressive symptoms at both time periods were defined as having chronic depression. Logistic mixed models were applied to compare growth curves and risk for overweight and underweight based on exposure to maternal depression.Results
We followed 181 infants to 24 months. At 12 and 24 months, respectively, 27.4% and 40.5% were overweight, and 5.6% and 2.2% were underweight. Exposure to chronic maternal depression was associated with underweight (OR = 12.12, 95%CI 1.86-78.78) and with reduced weight gain in the first 2 years of life (Coef = -0.48, 95% CI -0.94—0.01) compared with unexposed infants or infants exposed to episodic depression (depression at one time point). Exposure to chronic depression was also associated with reduced risk for overweight in the first 2 years of life (OR 0.28, 95%CI 0.03-0.92).Conclusions
Exposure to chronic maternal depression in the pre- and postnatal period was associated with reduced weight gain in the first two years of life and greater risk for failure to thrive, in comparison with unexposed infants or those exposed episodically. The infants of mothers with chronic depression may need additional nutritional monitoring and intervention. 相似文献17.
Chen X Gorlov IP Ying J Merriman KW Kimmel M Lu C Reyes-Gibby CC Gorlova OY 《PloS one》2012,7(3):e32644
Background
Detection of early stage non-small cell lung cancer (NSCLC) is commonly believed to be incidental. Understanding the reasons that caused initial detection of these patients is important for early diagnosis. However, these reasons are not well studied.Methods
We retrospectively reviewed medical records of patients diagnosed with stage I or II NSCLC between 2000 and 2009 at UT MD Anderson Cancer Center. Information on suggestive LC-symptoms or other reasons that caused detection were extracted from patients'' medical records. We applied univariate and multivariate analyses to evaluate the association of suggestive LC-symptoms with tumor size and patient survival.Results
Of the 1396 early stage LC patients, 733 (52.5%) presented with suggestive LC-symptoms as chief complaint. 347 (24.9%) and 287 (20.6%) were diagnosed because of regular check-ups and evaluations for other diseases, respectively. The proportion of suggestive LC-symptom-caused detection had a linear relationship with the tumor size (correlation 0.96; with p<.0001). After age, gender, race, smoking status, therapy, and stage adjustment, the symptom-caused detection showed no significant difference in overall and LC-specific survival when compared with the other (non-symptom-caused) detection.Conclusion
Symptoms suggestive of LC are the number one reason that led to detection in early NSCLC. They were also associated with tumor size at diagnosis, suggesting early stage LC patients are developing symptoms. Presence of symptoms in early stages did not compromise survival. A symptom-based alerting system or guidelines may be worth of further study to benefit NSCLC high risk individuals. 相似文献18.
Martens GA Jiang L Verhaeghen K Connolly JB Geromanos SG Stangé G Van Oudenhove L Devreese B Hellemans KH Ling Z Van Schravendijk C Pipeleers DG Vissers JP Gorus FK 《PloS one》2010,5(12):e14214
Background and Methodology
Pancreatic beta cells show intercellular differences in their metabolic glucose sensitivity and associated activation of insulin production. To identify protein markers for these variations in functional glucose sensitivity, rat beta cell subpopulations were flow-sorted for their level of glucose-induced NAD(P)H and their proteomes were quantified by label-free data independent alternate scanning LC-MS. Beta cell-selective proteins were also identified through comparison with rat brain and liver tissue and with purified islet alpha cells, after geometrical normalization using 6 stably expressed reference proteins.Principal Findings
All tissues combined, 943 proteins were reliably quantified. In beta cells, 93 out of 467 quantifiable proteins were uniquely detected in this cell type; several other proteins presented a high molar abundance in beta cells. The proteome of the beta cell subpopulation with high metabolic and biosynthetic responsiveness to 7.5 mM glucose was characterized by (i) an on average 50% higher expression of protein biosynthesis regulators such as 40S and 60S ribosomal constituents, NADPH-dependent protein folding factors and translation elongation factors; (ii) 50% higher levels of enzymes involved in glycolysis and in the cytosolic arm of the malate/aspartate-NADH-shuttle. No differences were noticed in mitochondrial enzymes of the Krebs cycle, beta-oxidation or respiratory chain.Conclusions
Quantification of subtle variations in the proteome using alternate scanning LC-MS shows that beta cell metabolic glucose responsiveness is mostly associated with higher levels of glycolytic but not of mitochondrial enzymes. 相似文献19.
20.
Christina B?chle Andrea Icks Klaus Stra?burger Marion Flechtner-Mors Andreas Hungele Peter Beyer Kerstin Placzek Ulrich Hermann Andrea Schumacher Markus Freff Anna Stahl-Pehe Reinhard W. Holl Joachim Rosenbauer 《PloS one》2013,8(8)