tbuckley/cabot-search huggingface dataset:
Marked Differences in Antidepressant Use by Race in an Elderly Community Sample: 1986–1996
Authors: D G Blazer, C F Hybels, E M Simonsick, J T Hanlon
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Prescriptions of antidepressant medications have increased significantly over the past 15 years across the life cycle. One overall correlate of medication use in older adults is race, with African Americans using fewer medications than whites. Given the frequency of depressive symptoms among elderly populations, as well as the increased potential for adverse side effects from antidepressants, the relative contribution of race in the use of antidepressants is critical for determining well-designed studies. The authors analyzed data from a community-based cohort of elders followed for 10 years to determine the association of race to the use of antidepressants between 1986 and 1996, with control for known correlates of depression in late life.METHOD: Information on antidepressant use and demographic and health characteristics were obtained from a stratified, probability-based sample of 4,162 elders (equally distributed between African American and white community-dwelling subjects) in the Piedmont region of North Carolina during four in-person interviews spanning 10 years. Descriptive statistics were calculated. Logistic regression was used for the final models.RESULTS: A total of 4.6% of whites and 2.3% of African Americans used antidepressants in 1986. Approximately 14.3% of whites and 5.0% of African Americans used antidepressants in 1996. In controlled analyses, the prevalence odds ratio for antidepressant use in whites, compared to African Americans, was 1.76 in 1986 and 3.77 in 1996.CONCLUSIONS: African American elders are much less likely to take antidepressants, and the difference in use increased over the 10 years of the survey.
Indications of BAL, lung biopsy, or both in mechanically ventilated patients with unexplained infiltrations
Authors: L. Papazian, M. Gainnier
Journal: European Respiratory Journal (2003)

The diagnosis of unexplained infiltrations in mechanically ventilated patients is a major problem in intensive care unit (ICU) patients.

In this issue of the European Respiratory Journal , Bulpa et al. 1 report the results of 38 mechanically ventilated patients who underwent bronchoalveolar lavage (BAL) combined with transbronchial biopsy (TBB) for the diagnosis of lung infiltrates. They obtained a diagnosis in 74% of the patients, which altered the treatment in 63% of the patients. The diagnostic performance was equally effective in both immunocompetent and immunosuppressed patients.

BAL is a firstline examination with many advantages, including a large sampled lung area and sufficient fluid return to perform multiple analyses. Indeed, cytology (percentage of neutrophils, siderophages, eosinophils and presence of malignant cells), a Gram stain, and numerous cultures (bacteriology, mycology, virology) can be performed. BAL is one of the best tools to establish the diagnosis of bacterial ventilator-associated pneumonia. BAL was evaluated in mechanically ventilated patients by Aubas et al. 2, who found a sensitivity of 89% and a specificity of 83% when using clinical and radiological criteria. When compared with histological criteria, at a threshold of 104 colony forming units (cfu)·mL−1, BAL exhibited a sensitivity of 47–58% 3–5. Its sensitivity can reach 91% in patients not receiving antibiotics 6. The specificity of BAL varies from 45–100% when compared with histological examination 3–6.

When diffuse infiltrates are present, a definite diagnosis can be difficult to establish, especially in acute respiratory distress syndrome (ARDS) patients. Therefore, histological diagnosis could be useful when BAL does not contribute to the diagnosis in the following two …
Outcome of low back pain in general practice: a prospective study
Authors: P. R Croft, G. J Macfarlane, A. C Papageorgiou, E. Thomas, A. J Silman
Journal: BMJ (1998)

To investigate the claim that 90% of episodes of low back pain that present to general practice have resolved within one month.Prospective study of all adults consulting in general practice because of low back pain over 12 months with follow up at 1 week, 3 months, and 12 months after consultation.Two general practices in south Manchester. 490 subjects (203 men, 287 women) aged 18-75 years.Proportion of patients who have ceased to consult with low back pain after 3 months; proportion of patients who are free of pain and back related disability at 3 and 12 months.Annual cumulative consultation rate among adults in the practices was 6.4%. Of the 463 patients who consulted with a new episode of low back pain, 275 (59%) had only a single consultation, and 150 (32%) had repeat consultations confined to the 3 months after initial consultation. However, of those interviewed at 3 and 12 months follow up, only 39/188 (21%) and 42/170 (25%) respectively had completely recovered in terms of pain and disability.The results are consistent with the interpretation that 90% of patients with low back pain in primary care will have stopped consulting with symptoms within three months. However most will still be experiencing low back pain and related disability one year after consultation.
cMET and Phospho-cMET Protein Levels in Breast Cancers and Survival Outcomes
Authors: Kanwal P. Raghav, Wenting Wang, Shuying Liu, Mariana Chavez-MacGregor, Xiaolong Meng, Gabriel N. Hortobagyi, Gordon B. Mills, Funda Meric-Bernstam, George R. Blumenschein, Ana M. Gonzalez-Angulo
Journal: Clinical Cancer Research (2012)

Abstract Purpose: To evaluate cMET (mesenchymal–epithelial transition factor gene) and phospho-cMET (p-cMET) levels in breast cancer subtypes and its impact on survival outcomes. Experimental Design: We measured protein levels of cMET and p-cMET in 257 breast cancers using reverse phase protein array. Regression tree method and Martingale residual plots were applied to find best cutoff point for high and low levels. Kaplan–Meier survival curves were used to estimate relapse-free (RFS) and overall (OS) survival. Cox proportional hazards models were fit to determine associations of cMET/p-cMET with outcomes after adjustment for other characteristics. Results: Median age was 51 years. There were 140 (54.5%) hormone receptor (HR) positive, 53 (20.6%) HER2 positive, and 64 (24.9%) triple-negative tumors. Using selected cutoffs, 181 (70.4%) and 123 (47.9%) cancers had high levels of cMET and p-cMET, respectively. There were no significant differences in mean expression of cMET (P &amp;lt; 0.128) and p-cMET (P &amp;lt; 0.088) by breast cancer subtype. Dichotomized cMET and p-cMET level was a significant prognostic factor for RFS [HR: 2.44, 95% confidence interval (CI): 1.34–4.44, P = 0.003 and HR: 1.64, 95% CI: 1.04–2.60, P = 0.033] and OS (HR: 3.18, 95% CI: 1.43–7.11, P = 0.003 and HR: 1.92, 95% CI: 1.08–3.44, P = 0.025). Within breast cancer subtypes, high cMET levels were associated with worse RFS (P = 0.014) and OS (P = 0.006) in HR-positive tumors, and high p-cMET levels were associated with worse RFS (P = 0.019) and OS (P = 0.014) in HER2-positive breast cancers. In multivariable analysis, patients with high cMET had a significantly higher risk of recurrence (HR: 2.06, 95% CI: 1.08–3.94, P = 0.028) and death (HR: 2.81, 95% CI: 1.19–6.64, P = 0.019). High p-cMET level was associated with higher risk of recurrence (HR: 1.79, 95% CI: 1.08–2.95.77, P = 0.020). Conclusions: High levels of cMET and p-cMET were seen in all breast cancer subtypes and correlated with poor prognosis. Clin Cancer Res; 18(8); 2269–77. ©2012 AACR.
Temozolomide-Mediated Radiation Enhancement in Glioblastoma: A Report on Underlying Mechanisms
Authors: Arnab Chakravarti, Michael G. Erkkinen, Ulf Nestler, Roger Stupp, Minesh Mehta, Ken Aldape, Mark R. Gilbert, Peter McL. Black, Jay S. Loeffler
Journal: Clinical Cancer Research (2006)

Abstract Purpose: In this study, we investigated the mechanisms by which temozolomide enhances radiation response in glioblastoma cells. Experimental Design: Using a panel of four primary human glioblastoma cell lines with heterogeneous O6-methylguanine-DNA methyltransferase (MGMT) protein expression, normal human astrocytes, and U87 xenografts, we investigated (a) the relationship of MGMT status with efficacy of temozolomide-based chemoradiation using a panel of in vitro and in vivo assays; (b) underlying mechanisms by which temozolomide enhances radiation effect in glioblastoma cells; and (c) strategies to overcome resistance to radiation + temozolomide. Results: Temozolomide enhances radiation response most effectively in glioblastomas without detectable MGMT expression. On concurrent radiation + temozolomide administration in MGMT-negative glioblastomas, there seems to be decreased double-strand DNA (dsDNA) repair capacity and enhanced dsDNA damage compared either with radiation alone or with sequentially administered temozolomide. Our data suggest that O6-benzylguanine can enhance the antitumor effects of concurrent radiation + temozolomide in MGMT-positive cells by enhancing apoptosis and the degree of dsDNA damage. O6-Benzylguanine was most effective when administered concurrently with radiation + temozolomide and had less of an effect when administered with temozolomide in the absence of radiation or when administered sequentially with radiation. Our in vivo data using U87 xenografts confirmed our in vitro findings. Conclusions: The present study shows that temozolomide enhances radiation response most effectively in MGMT-negative glioblastomas by increasing the degree of radiation-induced double-strand DNA damage. In MGMT-positive glioblastomas, depletion of MGMT by the addition of O6-benzylguanine significantly enhances the antitumor effect of concurrent radiation + temozolomide. These are among the first data showing mechanisms of synergy between radiation and temozolomide and the effect of MGMT.
Neuronal Angiotensin II Type 1 Receptor Upregulation in Heart Failure
Authors: Dongmei Liu, Lie Gao, Shyamal K. Roy, Kurtis G. Cornish, Irving H. Zucker
Journal: Circulation Research (2006)

Chronic heart failure (CHF) is a leading cause of mortality in developed countries. Angiotensin II (Ang II) plays an important role in the development and progression of CHF. Many of the important functions of Ang II are mediated by the Ang II type 1 receptor (AT 1 R), including the increase in sympathetic nerve activity in CHF. However, the central regulation of the AT 1 R in the setting of CHF is not well understood. This study investigated the AT 1 R in the rostral ventrolateral medulla (RVLM) of rabbits with CHF, its downstream pathway, and its gene regulation by the transcription factor activator protein 1 (AP-1). Studies were performed in 5 groups of rabbits: sham (n=5), pacing-induced (3 to 4 weeks) CHF (n=5), CHF with intracerebroventricular (ICV) losartan treatment (n=5), normal with ICV Ang II treatment (n=5), and normal with ICV Ang II plus losartan treatment (n=5). AT 1 R mRNA and protein expressions, plasma Ang II, and AP-1–DNA binding activity were significantly higher in RVLM of CHF compared with Sham rabbits (240.4±30.2%, P &lt;0.01; 206.6±25.8%, P &lt;0.01; 280±36.5%, P &lt;0.05; 207±16.4%, P &lt;0.01, respectively). Analysis of the stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) pathway showed that phosphorylated c-Jun proteins, phosphorylated JNK proteins, and JNK activity increased significantly in RVLM of CHF compared with sham (262.9±48.1%, 213.8±27.7%, 148.2±10.1% of control, respectively). Importantly, ICV losartan in CHF rabbits attenuated these increases. ICV Ang II in normal rabbits simulated the molecular changes seen in CHF. This effect was blocked by concomitant ICV losartan. In addition, Ang II–induced AT 1 R expression was blocked by losartan and a JNK inhibitor, but not by extracellular signal-regulated kinase or p38 MAP kinase inhibitors in a neuronal cell culture. These data suggest that central Ang II activates the AT 1 R, SAPK/JNK pathway. AP-1 may further regulate gene expression in RVLM in the CHF state.
A Phase II and Biomarker Study of Ramucirumab, a Human Monoclonal Antibody Targeting the VEGF Receptor-2, as First-Line Monotherapy in Patients with Advanced Hepatocellular Cancer
Authors: Andrew X. Zhu, Richard S. Finn, Mary Mulcahy, Jayne Gurtler, Weijing Sun, Jonathan D. Schwartz, Rita P. Dalal, Adarsh Joshi, Rebecca R. Hozak, Yihuan Xu, Marek Ancukiewicz, Rakesh K. Jain, Francis W. Nugent, Dan G. Duda, Keith Stuart
Journal: Clinical Cancer Research (2013)

To assess the efficacy and safety of the anti-VEGF receptor-2 (VEGFR-2) antibody ramucirumab as first-line therapy in patients with advanced hepatocellular carcinoma and explore potential circulating biomarkers.
Prognosis for South Asian and white patients newly admitted to hospital with heart failure in the United Kingdom: historical cohort study
Authors: H. M Blackledge
Journal: BMJ (2003)

To compare patterns of admission to hospital and prognosis in white and South Asian patients newly admitted with heart failure, and to evaluate the effect of personal characteristics and comorbidity on outcome.Historical cohort study.UK district health authority (population 960,000).5789 consecutive patients newly admitted with heart failure.Population admission rates, incidence rates for first admission with heart failure, survival, and readmission rates.When compared with the white population, South Asian patients had significantly higher age adjusted admission rates (rate ratio 3.8 for men and 5.2 for women) and hospital incidence rates (2.2 and 2.9). Among 5789 incident cases of heart failure, South Asian patients were younger and more often male than white patients (70 (SD 0.6) v 78 (SD 0.1) years and 56.5% (190/336) v 49.3% (2494/5057)). South Asian patients were also more likely to have previous myocardial infarction (10.1% (n = 34) v 5.5% (n = 278)) or concomitant myocardial infarction (18.8% (n = 63) v 10.7% (n = 539)) or diabetes (45.8% (n = 154) v 16.2% (n = 817), all P < 0.001). A trend was shown to longer unadjusted survival for both sexes among South Asian patients. After adjustment for covariables, South Asian patients had a significantly lower risk of death (hazard ratio 0.82, 95% confidence interval 0.68 to 0.99) and a similar probability of death or readmission (0.96, 0.81 to 1.09) compared with white patients.Population admission rates for heart failure are higher among South Asian patients than white patients in Leicestershire. At first admission South Asian patients were younger and more often had concomitant diabetes or acute ischaemic heart disease than white patients. Despite major differences in personal characteristics and risk factors between white and South Asian patients, outcome was similar, if not better, in South Asian patients.
Adverse events in patients with rheumatoid arthritis treated with infliximab in daily clinical practice
Authors: N Neven
Journal: Annals of the Rheumatic Diseases (2005)

In conclusion, infliximab can be used safely in daily clinical practice, but both doctors and patients should be aware of the (infection) risks, especially in patients receiving a higher dose (.3 mg/kg) of infliximab, in order to anticipate and minimise these risks.
Mechanics of turning and jumping and skier speed are associated with injury risk in men's World Cup alpine skiing: a comparison between the competition disciplines
Authors: Matthias Gilgien, Jörg Spörri, Josef Kröll, Philip Crivelli, Erich Müller
Journal: British Journal of Sports Medicine (2014)

Background/aim In alpine ski racing, there is limited information about skiers’ mechanical characteristics and their relation to injury risk, in particular for World Cup (WC) competitions. Hence, current findings from epidemiological and qualitative research cannot be linked to skiers’ mechanics. This study was undertaken to investigate whether recently reported differences in numbers of injuries per 1000 runs for competition disciplines can be explained by differences in the skiers’ mechanics. Methods During seven giant slalom, four super-G and five downhill WC competitions, mechanical characteristics of a forerunner were captured using differential global navigation satellite technology and a precise terrain surface model. Finally, the discipline-specific skiers’ mechanics were compared with the respective number of injuries per hour skiing. Results While the number of injuries per hour skiing was approximately equal for all disciplines, kinetic energy, impulse, run time, turn radius and turn speed were significantly different and increased from giant slalom to super-G and downhill. Turn ground reaction forces were largest for giant slalom, followed by super-G and downhill. The number of jumps was doubled from super-G to downhill. Conclusions Associating the number of injuries per hour in WC skiing with skiers’ mechanical characteristics, injuries in super-G and downhill seem to be related to increased speed and jumps, while injuries in giant slalom may be related to high loads in turning. The reported differences in the number of injuries per 1000 runs might be explained by a bias in total exposure time per run and thus potentially by emerged fatigue.
Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation tests
Authors: N Berkman
Journal: Thorax (2005)

<b>Background:</b> Bronchial provocation tests such as exercise, methacholine (MCH), and adenosine-5′-monophosphate (AMP) challenges are used extensively in the diagnosis of asthma. A study was undertaken to determine whether exhaled nitric oxide (eNO) can be used to diagnose asthma in patients with non-specific respiratory symptoms and to compare this test with conventional provocation tests. <b>Methods:</b> Patients with non-specific respiratory symptoms and normal spirometric parameters were included in the study. eNO was measured and exercise, MCH and AMP challenges performed in all subjects. Patients were defined as asthmatic based on clinical follow up 24 months after testing. <b>Results:</b> Forty patients were considered asthmatic and 45 were not. The area under receiver operating characteristic curves gave values of 0.896 for eNO, 0.781 for exercise, 0.924 for MCH, and 0.939 for AMP (p = 0.033, 0.575 and 0.085 for eNO <i>v</i> exercise, MCH and AMP respectively). From our data, a cut off value of NO &gt;7 ppb at a flow rate of 250 ml/s best differentiates between asthmatics and non-asthmatics (sensitivity 82.5%, specificity 88.9%). Optimal cut off values for other tests were exercise: ΔFEV<sub>1</sub> ⩾10% (sensitivity 57.9%, specificity 100%); PC<sub>20</sub>-MCH: ⩽3 mg/ml (sensitivity 87.5%, specificity 86.7%); and PC<sub>20</sub>-AMP: ⩽150 mg/ml (sensitivity 89.5%, specificity 95.6%). <b>Conclusions:</b> Measurement of eNO can be used as a safe, simple and rapid test for the diagnosis of asthma and is as good as bronchial provocation tests.
Phase I dose-finding and pharmacokinetic study of docetaxel and vinorelbine as first-line chemotherapy for metastatic breast cancer
Authors: M. Campone, P. Fumoleau, V. Delecroix, R. Deporte-Fety, G. Perrocheau, L. Vernillet, O. Borg-Olivier, J.P. Louboutin, M.-C. Bissery, A. Riva, N. Azli
Journal: Annals of Oncology (2001)
Radioimmunotherapy of Fibroblast Activation Protein Positive Tumors by Rapidly Internalizing Antibodies
Authors: Eliane Fischer, Krishna Chaitanya, Thomas Wüest, Andreas Wadle, Andrew M. Scott, Maries van den Broek, Roger Schibli, Stefan Bauer, Christoph Renner
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Fibroblast activation protein (FAP) is a serine protease that has emerged as a promising target for cancer therapy, either by direct abrogation of its proinvasive activity or by specific targeting of FAP-expressing cells with cytotoxic immunoconjugates. We aimed to select novel human–mouse cross-reactive antibodies and to test suitability for tumor therapy as radioimmunoconjugates in a preclinical model. Experimental Design: Human Fab fragments that bind to human and murine FAP were selected from an antibody phage library. Two candidates (ESC11 and ESC14) were engineered into fully human IgG1 antibodies and further characterized. We investigated the intracellular trafficking of ESC11 and ESC14 in live cells by confocal microscopy and analyzed the biodistribution and therapeutic effects of anti-FAP antibodies labeled with the β-emitting radionuclide 177Lu in a melanoma xenograft nude mouse model. Results were compared with vF19, a humanized variant of an anti-FAP antibody that has been previously used in clinical trials. Results: The two antibodies bound selectively to both human and mouse FAP, with affinities in the low nanomolar range. Binding to FAP-expressing melanoma cells resulted in rapid internalization of FAP-antibody complexes. 177Lu-labeled ESC11 specifically accumulated in melanoma xenografts in vivo, with a higher tumor uptake than ESC14 and vF19. Radioimmunotherapy with 8 MBq 177Lu-labeled anti-FAP antibodies delayed growth of established tumors, whereas 177Lu-ESC11 extended mouse survival more pronounced than 177Lu-ESC14 and 177Lu-vF19. Conclusion: Our results show the potential of ESC11 and ESC14 as potent radioimmunoconjugates or antibody–drug conjugates for diagnostic and therapeutic use in patients with FAP-expressing tumors. Clin Cancer Res; 18(22); 6208–18. ©2012 AACR.
Disorders of Iron Metabolism
Authors: N C Andrews
Journal: New England Journal of Medicine (1999)

Iron has the capacity to accept and donate electrons readily, interconverting between ferric (Fe2+) and ferrous (Fe3+) forms. This capability makes it a useful component of cytochromes, oxygen-binding molecules (i.e., hemoglobin and myoglobin), and many enzymes. However, iron can also damage tissues by catalyzing the conversion of hydrogen peroxide to free-radical ions that attack cellular membranes, proteins, and DNA. Proteins sequester iron to reduce this threat. Iron ions circulate bound to plasma transferrin and accumulate within cells in the form of ferritin. Iron protoporphyrin (heme) and iron–sulfur clusters serve as enzyme cofactors. Under normal circumstances, only trace amounts . . .
Relationship of the erythrocyte sedimentation rate to acute phase proteins in polymyalgia rheumatica and giant cell arteritis
Authors: J. R. Park, J. G. Jones, B. L. Hazleman
Journal: Annals of the Rheumatic Diseases (1981)

We have compared the erythrocyte sedimentation rate (ESR) with other acute phase proteins (C-reactive protein (CRP), α<sub>1</sub> antitrypsin, orosomucoid, and haptoglobin) in 108 patients with polymyalgia rheumatica and/or giant cell arteritis. There was good correlation between CRP and ESR, but the ESR was also found to have the highest correlation with disease activity. The additional measurement of CRP or other acute phase proteins may be of value in a minority of cases.