tbuckley/cabot-search huggingface dataset:
Serum Soluble Epidermal Growth Factor Receptor Concentrations Decrease in Postmenopausal Metastatic Breast Cancer Patients Treated with Letrozole
Authors: Jacqueline M. Lafky, Andre T. Baron, Elsa M. Cora, David W. Hillman, Vera J. Suman, Edith A. Perez, James N. Ingle, Nita J. Maihle
Journal: Cancer Research (2005)

Abstract Previous studies have implicated estrogen as a regulator of epidermal growth factor receptor (EGFR) expression in breast tumors. We therefore speculated that estrogen might modulate serologic soluble EGFR (sEGFR) concentrations in breast cancer patients. Accordingly, we measured serum sEGFR concentrations in postmenopausal women with metastatic breast cancer (MBC) treated with letrozole, an aromatase inhibitor that blocks estrogen synthesis. Serum specimens were obtained prior to and following 1 and 3 months of letrozole therapy. We report that sEGFR concentrations do not differ between MBC patients prior to letrozole treatment and age- and postmenopause-matched healthy women (P = 0.468). In contrast, however, sEGFR concentrations decreased significantly in 76% of MBC patients after both 1 month (P = 0.006) and 3 months (P = 0.003) of letrozole therapy versus pretreatment concentrations. Within the limitations of this study, we found no evidence for an association between pretreatment sEGFR concentrations or decreased treatment sEGFR concentrations and either progression-free or overall survival. Nonetheless, we conclude that future prospective studies are warranted to determine if baseline and/or longitudinal serum sEGFR concentrations may be useful for predicting disease progression and survival, and/or for monitoring responsiveness to aromatase inhibitors or other endocrine therapies in breast cancer patients.
Do we need treatment with tumour necrosis factor blockers for giant cell arteritis?
Authors: C. Salvarani, N. Pipitone, L. Boiardi, G. G Hunder
Journal: Annals of the Rheumatic Diseases (2007)

For many years glucocorticoids (GCs) have been known to effectively suppress the clinical manifestations of giant cell arteritis (GCA), and prevent its ischaemic complications. GCs are still the treatment of choice for this disease. It is recommended that GC therapy be commenced as soon as the diagnosis of GCA is established. An initial dose of 40–60 mg/daily of prednisone (or equivalent) as a single or divided dose is generally found to be adequate in the vast majority of the cases.1 2 Higher-dose pulse GC therapy has been advocated by some for patients with recent or pending visual disturbances, but an observational study and a randomised controlled trial (RCT) failed to demonstrate superiority of pulse over oral GC therapy in preventing ischaemic complications.3 4

The initial dose of GCs is usually given for 2 to 4 weeks until all reversible signs and symptoms have resolved and acute phase reactants are back to normal. Subsequently, the dose can be gradually reduced every 1–2 weeks by a maximum of 10% of the total daily dose. Because of the variability of the course of GCA, no fixed rules have been established regarding treatment duration. Most patients are treated for 1–2 years, but some with a prolonged or relapsing course may require low doses of GCs for several years.5–7 Clinical flares usually occur when the prednisone (or equivalent) dose is reduced to approximately 5–10 mg/daily.7–9 The benefit conferred by GCs needs to be balanced against the common and well recognised complications related to long-term GC use. In a population-based study of 120 patients with GCA, 86% of patients had adverse events including bone fractures, avascular necrosis of the hip, diabetes mellitus, infections, gastrointestinal bleeding, and cataract.7 Adverse events were related to the age of patients and …
Metastasis Suppressor KISS1 Seems to Reverse the Warburg Effect by Enhancing Mitochondrial Biogenesis
Authors: Wen Liu, Benjamin H. Beck, Kedar S. Vaidya, Kevin T. Nash, Kyle P. Feeley, Scott W. Ballinger, Keke M. Pounds, Warren L. Denning, Anne R. Diers, Aimee Landar, Animesh Dhar, Tomoo Iwakuma, Danny R. Welch
Journal: Cancer Research (2013)

Abstract Cancer cells tend to utilize aerobic glycolysis even under normoxic conditions, commonly called the “Warburg effect.” Aerobic glycolysis often directly correlates with malignancy, but its purpose, if any, in metastasis remains unclear. When wild-type KISS1 metastasis suppressor is expressed, aerobic glycolysis decreases and oxidative phosphorylation predominates. However, when KISS1 is missing the secretion signal peptide (ΔSS), invasion and metastasis are no longer suppressed and cells continue to metabolize using aerobic glycolysis. KISS1-expressing cells have 30% to 50% more mitochondrial mass than ΔSS-expressing cells, which are accompanied by correspondingly increased mitochondrial gene expression and higher expression of PGC1α, a master coactivator that regulates mitochondrial mass and metabolism. PGC1α-mediated downstream pathways (i.e., fatty acid synthesis and β-oxidation) are differentially regulated by KISS1, apparently reliant upon direct KISS1 interaction with NRF1, a major transcription factor involved in mitochondrial biogenesis. Since the downstream effects could be reversed using short hairpin RNA to KISS1 or PGC1α, these data appear to directly connect changes in mitochondria mass, cellular glucose metabolism, and metastasis. Cancer Res; 74(3); 954–63. ©2013 AACR.
Audit on osteoporosis assessment in patients with COPD
Authors: Rajesh Yadavilli, Nicola Garner, Diana Lees, Mithun Murthy, Hassan Burhan
Journal: European Respiratory Journal (2013)

Introduction and Objectives: 

NICE guidelines 2010 for Chronic obstructive pulmonary disease1 (COPD) management states that all patients treated with long-term oral corticosteroids should be monitored for the development of osteoporosis and given appropriate prophylaxis. Prophylactic treatment should be started without monitoring in patients over the age of 651. Patients treated with high-dose inhaled corticosteroids are also at risk of developing osteoporosis.

Methods: 

50 inpatient admissions with exacerbation of COPD were reviewed retrospectively for the monitoring of osteoporosis at Royal Liverpool Teaching hospital.

Results: 

22 were Male, Mean Age-69yrs, Average smoking history-48 Pack years.

18 patients in total have received prophylaxis for osteoporosis.

29 patients were aged >65 yrs and 10 (34%) of these were receiving prophylactic treatment for osteoporosis.

8 out of 21(38%) patients aged <65 yrs were receiving prophylactic treatment and only 2 of them were investigated with bone scans.

Of the 21 patients aged  2 per year and all carried the risk factor of smoking.

Conclusions: 

Osteoporosis in COPD patients is under investigated and possibly, under treated.

All COPD patients below 65 yrs of age should have risk assessment for osteoporosis every year.

We are developing a summary sheet that includes risk estimation of osteoporosis for all COPD patients admitted to hospital or treated in Accident & Emergency. High risk patients should be investigated with Bone mineral density scan and treated if found to have osteoporosis.

References: 

1. CG101, Chronic obstructive pulmonary disease: NICE guideline; 21 June 2010.
Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase
Authors: Sarah E. Ewald, Alex Engel, Jiyoun Lee, Miqi Wang, Matthew Bogyo, Gregory M. Barton
Journal: The Journal of Experimental Medicine (2011)

Toll-like receptor (TLR) 9 requires proteolytic processing in the endolysosome to initiate signaling in response to DNA. However, recent studies conflict as to which proteases are required for receptor cleavage. We show that TLR9 proteolysis is a multistep process. The first step removes the majority of the ectodomain and can be performed by asparagine endopeptidase (AEP) or cathepsin family members. This initial cleavage event is followed by a trimming event that is solely cathepsin mediated and required for optimal receptor signaling. This dual requirement for AEP and cathepsins is observed in all cell types that we have analyzed, including mouse macrophages and dendritic cells. In addition, we show that TLR7 and TLR3 are processed in an analogous manner. These results define the core proteolytic steps required for TLR9 function and suggest that receptor proteolysis may represent a general regulatory strategy for all TLRs involved in nucleic acid recognition.
Mann-Whitney test is not just a test of medians: differences in spread can be important
Authors: A. Hart
Journal: BMJ (2001)

The Mann-Whitney (or Wilcoxon-Mann-Whitney) test is sometimes used for comparing the efficacy of two treatments in clinical trials. It is often presented as an alternative to a t test when the data are not normally distributed. Whereas a t test is a test of population means, the Mann-Whitney test is commonly regarded as a test of population medians. This is not strictly true, and treating it as such can lead to inadequate analysis of data.

#### Summary points

The Mann-Whitney test is used as an alternative to a t test when the data are not normally distributed

The test can detect differences in shape and spread as well as just differences in medians

Differences in population medians are often accompanied by equally important differences in shape

Researchers should describe the clinically important features of data and not just quote a P value

The Mann-Whitney test is a test of both location and shape. Given two independent samples, it tests whether one variable tends to have values higher than the other. As Altman states, one form of the test statistic is an estimate of the probability that one variable is less than the other,1 although this statistic is not output by many statistical packages. In the case where the only distributional difference is a shift in location, this can indeed be described as a difference in medians. Hence, for example, the online help facility in Minitab 10.51 states that the Mann-Whitney test is “a two-sample rank test for the difference between two population medians … It assumes that the data are independent random samples from two populations that have the same shape.” Figure 1 shows two distributions for which this is the case. One distribution is shifted 0.75 units …
Magnetic resonance analysis of abnormal diaphragmatic motion in patients with emphysema
Authors: T. Iwasawa, S. Kagei, T. Gotoh, Y. Yoshiike, K. Matsushita, H. Kurihara, K. Saito, S. Matsubara
Journal: European Respiratory Journal (2002)

The purpose of this study was to quantitatively evaluate paradoxical diaphragmatic motion using magnetic resonance (MR) imaging. A total of 27 subjects were examined, including 12 normal young adults, six control individuals, and nine patients with emphysema. With subjects in the supine position, 30 sequential sagittal MR images of the entire right lung were obtained during tidal and deep slow breathing. Diaphragmatic movement between sequential images was estimated as the displacement area and the total diaphragmatic movement in a respiratory cycle was calculated. The paradoxical motion of the diaphragm, representing the inverted movement to increase or decrease lung area, since paradoxical movement ratio (M pr =(total paradoxical diaphragmatic movement/total diaphragmatic movement)×100), was evaluated. In patients with emphysema, paradoxical diaphragmatic motion was observed on MR images during deep breathing. The mean M pr in emphysematous patients during deep breathing was 10±4%, which was significantly higher than 0.5±0.2% in young adults (p&lt;0.05), and 1.2±0.6% in aged-matched controls (p&lt;0.05). The present results indicate that magnetic resonance images could be used to detect paradoxical diaphragmatic motion in patients with emphysema.
Unusual pulmonary complication of ulcerative colitis with a rapid response to corticosteroids: case report.
Authors: G A Hilling, D A Robertson, A H Chalmers, H S Rigby
Journal: Gut (1994)

Extraintestinal features of ulcerative colitis are well recognised. Pulmonary complications include pulmonary vasculitis, fibrosing alveolitis, asthma, and chronic bronchial suppuration. A case is described of a patient with longstanding quiescent ulcerative colitis who developed a life threatening pulmonary complication, which is extremely sensitive to corticosteroid treatment.
Hand grip strength in patients engaged in pulmonary rehabilitation program during COPD exacerbation
Authors: Ozden Ozyemisci-Taskiran, Zeynep Erden, Nurdan Kokturk, Gulcin Kaymak Karatas
Journal: European Respiratory Journal (2011)

Aims:  To measure hand grip strengths and investigate related factors in COPD patients engaged in pulmonary rehabilitation program during exacerbation.   Material and methods:  Grip strengths of both hands were measured using vigorimetry in 52 COPD patients.   Results:  Mean hand grip strength were 0.41±0.14 bar. Patients were divided into two groups according to a cut-off point, 0.40 bar (54% ≤0.40, 46% >0.40), there was no significant difference in age, systemic diseases, FEV1/FVC, arterial blood gases between groups. Hand grip strengths were lower in women (p=0.003). In patients with lower strength, FEV1, FVC values (p=0.019 and p=0.002, respectively), hemoglobin levels, mini-nutritional scores and T scores at femoral neck were lower than that of patients with higher strength (p  There was a moderate positive correlation between grip strength and 6-minute walk distance (r=0.511, p=0.001). There were negative correlations between strength and rest duration and number (r=-0.339, p=0.03 and r=-0,464, p=0.002), saturation changes (r=-0.383, p=0.012), dyspnea and fatigue levels (r=-0.475, p=0.001) during the walk test.   Conclusion:  Hand grip strengths of COPD patients in exacerbation showed good correlation with 6-minute walk test, indicator of functional capacity. Hand grip strength measurement which is simple to perform and has low cost may be a helpful indicator of muscle performance, especially when 6-minute walk test can not be performed during exacerbation.
Trends in the prevalence of respiratory symptoms and treatment in Dutch children over a 12 year period: results of the fourth consecutive survey
Authors: M Mommers
Journal: Thorax (2005)

<b>Background:</b> Although there is considerable evidence that the prevalence of childhood asthma has increased over the last decades, it is not clear if this trend is still ongoing. A study was undertaken to investigate whether previously observed trends in the prevalence of respiratory symptoms, physician visits, medication use, and absence from school in Dutch children aged 8–9 years persisted in 2001. <b>Methods:</b> Parents of 1154 children aged 8–9 years eligible for a routine physical examination in 2001 were asked to complete a questionnaire on the respiratory health of their child. <b>Results:</b> In 2001, 1102 children (95.5%) participated in the survey. Similarly high response rates were obtained in the surveys of 1989, 1993 and 1997, with 1794, 1526 and 1670 children aged 8–9 years participating in the respective surveys. The decreasing trend previously observed for recent wheeze between 1989 and 1997 persisted into 2001, particularly in boys. After increasing between 1989 and 1997, the prevalence of shortness of breath with wheeze decreased between 1997 and 2001. The proportion of wheezy children using medication increased between 1989 and 2001 in boys (42.9% <i>v</i> 64.8%; p = 0.003), but the increase was not statistically significant in girls (34.0% <i>v</i> 45.7%; p = 0.096). <b>Conclusion:</b> The prevalence of recent wheeze in Dutch school children has declined steadily since 1989. The rising prevalence of medication use in symptomatic children over time may reflect better asthma control and may partly explain the concurrently decreasing trend in the prevalence of asthma symptoms in our study population.
Hidradenitis suppurativa: an-androgen-dependent disorder
Authors: F.J.G. EBLING
Journal: British Journal of Dermatology (1986)

Journal Article Hidradenitis suppurativa: an‐androgen‐dependent disorder Get access F.J.G. EBLING F.J.G. EBLING Sub‐Department of Dermatology, Academic Division of Medicine, Royal Hallamshire Hospital, Sheffield S1o 2JF, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue 3, 1 September 1986, Pages 259–262, https://doi.org/10.1111/j.1365-2133.1986.tb05739.x Published: 01 September 1986
Hyperplastic Lesions of Mouse Mammary Glands After Treatment With 3-Methylcholanthrene&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Faulkin Lj
Journal: JNCI Journal of the National Cancer Institute (1966)

Hyperplastic lesions were present in the mammary glands of mice treated with 3-methylcholanthrene and exogenous hormones. The lesions were similar to those found in glands that were exposed to mammary tumor virus. It is probable that the production of mammary gland hyperplastic lesions could serve as a measure of the effectiveness of a chemical compound as a carcinogenic agent for the mammary gland.
Sociopathy or hyper-masculinity?
Authors: Anne Campbell
Journal: Behavioral and Brain Sciences (1995)

Abstract Definitional slippage threatens to equate secondary sociopathy with mere criminality and leaves the status of noncriminal sociopaths ambiguous. Primary sociopathy appears to show more environmental contingency than would be implied by a strong genetic trait approach. A reinterpretation in terms of hypermasculinity and hypofemininity is compatible with the data.
Par-4 Binds to Topoisomerase 1 and Attenuates Its DNA Relaxation Activity
Authors: Anindya Goswami, Shirley Qiu, Thomas S. Dexheimer, Padhma Ranganathan, Ravshan Burikhanov, Yves Pommier, Vivek M. Rangnekar
Journal: Cancer Research (2008)

Abstract The regulation of DNA relaxation by topoisomerase 1 (TOP1) is essential for DNA replication, transcription, and recombination events. TOP1 activity is elevated in cancer cells, yet the regulatory mechanism restraining its activity is not understood. We present evidence that the tumor suppressor protein prostate apoptosis response-4 (Par-4) directly binds to TOP1 and attenuates its DNA relaxation activity. Unlike camptothecin, which binds at the TOP1-DNA interface to form cleavage complexes, Par-4 interacts with TOP1 via its leucine zipper domain and sequesters TOP1 from the DNA. Par-4 knockdown by RNA interference enhances DNA relaxation and gene transcription activities and promotes cellular transformation in a TOP1-dependent manner. Conversely, attenuation of TOP1 activity either by RNA interference or Par-4 overexpression impedes DNA relaxation, cell cycle progression, and gene transcription activities and inhibits transformation. Collectively, our findings suggest that Par-4 serves as an intracellular repressor of TOP1 catalytic activity and regulates DNA topology to suppress cellular transformation. [Cancer Res 2008;68(15):6190–8]
Lupus nephritis in children
Authors: N Baqi, S Moazami, A Singh, H Ahmad, S Balachandra, A Tejani
Journal: Journal of the American Society of Nephrology (1996)

There are only a few studies in the pediatric literature that have analyzed risk factors for renal failure in childhood lupus nephritis. This study reviewed the outcome of 56 children (4 to 18 yr of age) with lupus nephritis seen at the authors' institution over a 27-yr period (1965 to 1992), in relation to risk factors and therapy. All children underwent percutaneous renal biopsy before the institution of therapy. From 1965 to 1987, treatment for Class III and IV lupus nephritis consisted of high-dose pulse methylprednisolone, 500 mg daily for 10 days, followed by oral prednisone. From 1987 to 1992, IV cyclophosphamide was given monthly for 6 months and then every 3 months for a period of 3 yr for patients with Class III and Class IV disease. Of 56 children, 42% had Class IV and 21% had Class III histology at onset. The mean follow-up period was 4 yr and ranged from 0.5 to 20.3 yr. Life-table analysis showed that the cumulative proportion of patients surviving was 82.8% at 5 yr and 67.7% at 10 yr. Renal survival was 44.4% at 5 yr and 29% at 10 yr, after the initial diagnosis of lupus nephritis was made. Age at diagnosis, race, sex, initial serum creatinine level, and the presence of proteinuria, hypertension, and DNA antibody titers were reviewed with respect to disease progression, as was the histological class at diagnosis. The effect of the different therapies was also examined. Univariate analysis revealed a significant association of progression to ESRD with an elevated serum creatinine level (P = 0.021), decreased C3 complement (P = 0.024), hypertension (P = 0.053), and histological classification of Class IV lupus nephritis (P = 0.031). Multivariate analysis demonstrated that progression to ESRD was independently associated with an initial Class IV histology (relative risk, 1.78; P < 0.003), hypertension at presentation (relative risk, 1.67; P < 0.003), and a low C3 complement level in conjuction with a high creatinine level (relative risk, 1.52; P < 0.028). Among children with lupus nephritis, those with Class IV disease, hypertension, high creatinine levels, and low C3 complement levels at the time of diagnosis are at increased risk for ESRD. Initial histological classification of lupus nephritis was the most reliable prognostic factor for disease progression. This study was unable to detect a difference in outcome for the two treatment groups.
Mitochondrial Oxidative Stress Mediates Angiotensin II–Induced Cardiac Hypertrophy and Gαq Overexpression–Induced Heart Failure
Authors: Dao-Fu Dai, Simon C. Johnson, Jason J. Villarin, Michael T. Chin, Madeline Nieves-Cintrón, Tony Chen, David J. Marcinek, Gerald W. Dorn, Y. James Kang, Tomas A. Prolla, Luis F. Santana, Peter S. Rabinovitch
Journal: Circulation Research (2011)

Mitochondrial dysfunction has been implicated in several cardiovascular diseases; however, the roles of mitochondrial oxidative stress and DNA damage in hypertensive cardiomyopathy are not well understood.We evaluated the contribution of mitochondrial reactive oxygen species (ROS) to cardiac hypertrophy and failure by using genetic mouse models overexpressing catalase targeted to mitochondria and to peroxisomes.Angiotensin II increases mitochondrial ROS in cardiomyocytes, concomitant with increased mitochondrial protein carbonyls, mitochondrial DNA deletions, increased autophagy and signaling for mitochondrial biogenesis in hearts of angiotensin II-treated mice. The causal role of mitochondrial ROS in angiotensin II-induced cardiomyopathy is shown by the observation that mice that overexpress catalase targeted to mitochondria, but not mice that overexpress wild-type peroxisomal catalase, are resistant to cardiac hypertrophy, fibrosis and mitochondrial damage induced by angiotensin II, as well as heart failure induced by overexpression of Gαq. Furthermore, primary damage to mitochondrial DNA, induced by zidovudine administration or homozygous mutation of mitochondrial polymerase γ, is also shown to contribute directly to the development of cardiac hypertrophy, fibrosis and failure.These data indicate the critical role of mitochondrial ROS in cardiac hypertrophy and failure and support the potential use of mitochondrial-targeted antioxidants for prevention and treatment of hypertensive cardiomyopathy.