tbuckley/cabot-search huggingface dataset:
Metabolic surgery and obstructive sleep apnoea: the protective effects of bariatric procedures
Authors: Hutan Ashrafian, Carel W le Roux, Simon P Rowland, Mariam Ali, Andrew R Cummin, Ara Darzi, Thanos Athanasiou
Journal: Thorax (2011)

The global epidemic of obesity and the worldwide prevalence of obstructive sleep apnoea (OSA) are both increasing. Epidemiological studies reveal an association between obesity, weight gain and OSA. Metabolic or bariatric operations provide sustained weight loss and resolve or improve the symptoms of OSA in the majority of morbidly obese individuals. These operations also modulate the metabolic profile to improve glycaemic control, to decrease cardiovascular risk and obesity-related mortality. The beneficial effects of metabolic operations on OSA include mechanical weight-dependent and metabolic weight-independent effects that are achieved through the BRAVE effects: (<b>B</b>ile flow alteration; <b>R</b>eduction of gastric size; <b>A</b>natomical gut rearrangement and altered flow of nutrients; <b>V</b>agal manipulation; and <b>E</b>nteric gut hormone modulation). These result in an improvement in insulin resistance, adipokines, cytokines and systemic inflammation. A literature analysis was performed with statistical pooling of available surgical and medical studies to determine whether the weighted mean decrease in body mass index and sleep apnoea severity (measured by the apnoea-hypopnoea index) are larger in metabolic surgical studies than in non-surgical weight loss studies (diet, exercise and medication). However, heterogeneity across available trials, poor follow-up measures and a deficiency in comparative studies between surgical and non-surgical therapy precludes definitive statements regarding the relative benefits of surgical therapy. Further research is required to quantify robustly the effects and mechanisms of sleep apnoea resolution by metabolic surgery, which may reveal novel non-surgical treatments or enhanced surgical strategies in the management of this multisystem sleep disorder.
Validity of histopathological grading of articular cartilage from osteoarthritic knee joints
Authors: K. Ostergaard, C. B Andersen, J. Petersen, K. Bendtzen, D. M Salter
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVES</h3> To determine the validity of the histological-histochemical grading system (HHGS) for osteoarthritic (OA) articular cartilage. <h3>METHODS</h3> Human articular cartilage was obtained from macroscopically normal (n = 13) and OA (n = 21) knee joints. Sections of central and peripheral regions of normal samples were produced. Sections of regions containing severe, moderate, and mild OA changes were produced from each OA sample. A total of 89 sections were graded by means of the HHGS (0–14) twice by three observers. <h3>RESULTS</h3> Average scores for regions designated severe (8.64) and moderate (5.83) OA were less than the expected (10–14 and 6–9, respectively) according to the HHGS, whereas average scores for the region designated mild (5.29) OA and central and peripheral regions (2.19) of normal cartilage were higher than expected (2–5 and 0–1, respectively). The HHGS was capable of differentiating between articular cartilage from macroscopically normal and OA joints and between the region designated severe OA and other regions. However, the HHGS did not adequately differentiate between regions designated mild and moderate OA. Values for sensitivity, specificity, and efficiency for all regions varied considerably. <h3>CONCLUSION</h3> The HHGS is valid for normal and severe OA cartilage, but does not permit distinction between mild and moderate OA changes in articular cartilage.
Ødegaard’s Selection Hypothesis Revisited: Schizophrenia in Surinamese Immigrants to the Netherlands
Authors: Jean-Paul Selten, Elizabeth Cantor-Graae, Joris Slaets, René S. Kahn
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The incidence of schizophrenia among Surinamese immigrants to the Netherlands is high. The authors tested Ødegaard's hypothesis that this phenomenon is explained by selective migration. METHOD: The authors imagined that migration from Surinam to the Netherlands subsumed the entire population of Surinam and not solely individuals at risk for schizophrenia. They compared the risk of a first admission to a Dutch mental hospital for schizophrenia from 1983 to 1992 for Surinamese-born immigrants to the risk for Dutch-born individuals, using the Surinamese-born population in the Netherlands and the population of Surinam combined as the denominator for the immigrants. RESULTS: The age- and sex-adjusted relative risk of schizophrenia for the Surinamese-born immigrants was 1.46. CONCLUSIONS: Selective migration cannot solely explain the higher incidence of schizophrenia in Surinamese immigrants to the Netherlands.
Variability in Assessing Treatment Response: Metastatic Colorectal Cancer as a Paradigm
Authors: Binsheng Zhao, Shing M. Lee, Hyun-Ju Lee, Yongqiang Tan, Jing Qi, Thorsten Persigehl, David P. Mozley, Lawrence H. Schwartz
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The cutoff values currently used to categorize tumor response to therapy are neither biologically based nor tailored for measurement reproducibility with contemporary imaging modalities. Sources and magnitudes of discordance in response assessment in metastatic colorectal cancer (mCRC) are unknown. Experimental Design: A subset of patients' CT images of chest, abdomen, and pelvis were randomly chosen from a multicenter clinical trial evaluating insulin-like growth factor receptor type 1–targeted therapy in mCRC. Using Response Evaluation Criteria in Solid Tumors (RECIST), three radiologists selected target lesions and measured “uni” (maximal diameter), “bi” (product of maximal diameter and maximal perpendicular diameter), and “vol” (volume) on baseline and 6-week posttherapy scans in the following ways: (i) each radiologist independently selected and measured target lesions and (ii) one radiologist's target lesions were blindly remeasured by the others. Variability in relative change of tumor measurements was analyzed using linear mixed effects models. Results: Three radiologists independently selected 138, 101, and 146 metastatic target lesions in the liver, lungs, lymph nodes, and other organs (e.g., peritoneal cavity) in 29 patients. Of 198 target lesions total, 33% were selected by all three, 28% by two, and 39% by one radiologist. With independent selection, the variability in relative change of tumor measurements was 11% (uni), 19% (bi), and 22% (vol), respectively. When measuring the same lesions, the corresponding numbers were 8%, 14%, and 12%. Conclusions: The relatively low variability in change of mCRC measurements suggests that response criteria could be modified to allow more accurate and sensitive CT assessment of anticancer therapy efficacy. Clin Cancer Res; 20(13); 3560–8. ©2014 AACR.
Prevalence of Diabetes in Care Home Residents
Authors: Alan J. Sinclair, Roger Gadsby, Sue Penfold, Simon C.M. Croxson, Antony J. Bayer
Journal: Diabetes Care (2001)

To determine the prevalence of known and undetected diabetes diagnosed either by an elevated fasting baseline sample or by a 2-h post-glucose load sample in a group of residents of care homes in an urban-district setting.We completed individual interviews with patients and caregivers in 30 care homes (both residential and nursing homes) in two metropolitan districts of Birmingham, West Midlands, U.K. All care homes were under the supervision of primary care physicians (general practitioners). We carried out 75-g oral glucose tolerance tests (OGTTs) in consenting residents without previous known diabetes. Criteria for diagnosis of diabetes were obtained from the World Health Organization (1998) and the American Diabetes Association (1997).Of 636 residents available for study, 76 residents (12.0%) were known to have diabetes; of the 560 remaining residents, 286 either refused to participate or were deemed too ill or unavailable to undergo testing. Complete data on 274 OGTTs were obtained (median age 83 years, range 45-101). A total of 46 subjects were diagnosed as having diabetes and 94 as having impaired glucose tolerance. Allowing for subjects who refused or were unable to participate, the calculated total prevalence (which includes known and newly detected diabetes) was 26.7% (95% CI 21.9-32.0). The calculated overall prevalence of impaired glucose tolerance was 30.2% (25.2-35.6).In a group of care home residents not known to have diabetes and able to undergo testing, a substantial proportion have undetected diabetes based on a 2-h postglucose load. These residents warrant further study as they may be at higher cardiovascular risk and require an intervention.
A pilot study of subcutaneous decitabine in β-thalassemia intermedia
Authors: Nancy F. Olivieri, Yogen Saunthararajah, Vivek Thayalasuthan, Janet Kwiatkowski, Russell E. Ware, Frans A. Kuypers, Hae-Young Kim, Felicia L. Trachtenberg, Elliott P. Vichinsky
Journal: Blood (2011)
Will 1 April mark the beginning of the end of England's NHS? No
Authors: J. Le Grand
Journal: BMJ (2013)

The government's changes to the NHS in England come into force on 1 April. <b>David Hunter</b> argues that they will result in creeping privatisation and destroy the public service ethos but <b>Julian Le Grand</b> (doi:10.1136/bmj.f1951) thinks that more competition will improve the quality of care
Survival and long-term health and cognitive outcomes after low-grade glioma
Authors: Gregory T. Armstrong, Heather M. Conklin, Sujuan Huang, Deokumar Srivastava, Robert Sanford, David W. Ellison, Thomas E. Merchant, Melissa M. Hudson, Mary Ellen Hoehn, Leslie L. Robison, Amar Gajjar, E. Brannon Morris
Journal: Neuro-Oncology (2010)

Long-term morbidity for children with low-grade glioma (LGG) requires exposure-specific characterization. Overall survival (OS) and progression-free survival (PFS) were estimated for 361 children diagnosed with LGG between 1985 and 2007 at a single institution. Five-year survivors (n = 240) received risk-based clinical assessment. Cumulative incidence of late effects 15 years from diagnosis were estimated. Risk factors for adverse health were identified using Fine and Gray's approach to Cox's proportional hazards model, accounting for death as a competing risk. OS at 15 years was 86% (95% confidence interval [CI] 82%-90%), and PFS was 55% (95% CI 51%-58%). Among the 240 5-year survivors, the 5-, 10-, and 15-year cumulative incidence of adverse outcomes included blindness: 10%, 13%, and 18%, respectively; hearing loss: 8%, 14%, and 22%; obesity/overweight: 18%, 35%, and 53%; hyperinsulinism: 1%, 5%, and 24%; growth hormone deficiency: 13%, 27%, and 29%;thyroid hormone deficiency: 16%, 28%, and 33%; and adrenocorticotropic hormone (ACTH) deficiency: 12%, 22%, and 26%. Multivariable models demonstrated radiation therapy to be a significant independent predictor of hearing loss, growth hormone deficiency, abnormal thyroid function, and ACTH deficiency. Diencephalic location was a statistically significant independent risk factor for blindness, growth hormone deficiency, abnormal thyroid function, and ACTH deficiency. Among the 182 5-year survivors assessed for intellectual function, 34% had an intelligence quotient (IQ) below average (<85), associated with younger age at diagnosis, epilepsy, and shunt placement. Survivors of childhood LGG experience substantial long-term adverse effects that continue to increase well beyond the 5-year survival time point.
Anticardiolipin Antibodies and Recurrent Coronary Events
Authors: Androniki Bili, Arthur J. Moss, Charles W. Francis, Wojciech Zareba, Luc F. Miller Watelet, Ignacio Sanz, for the Thrombogenic Factors, Recurrent Coronary Events Investigators
Journal: Circulation (2000)

Background —The association of anticardiolipin (aCL) antibodies with coronary artery disease has been shown in several studies but remains controversial. We evaluated the association of aCL and anti–β 2 -glycoprotein I (aβ 2 GPI) antibodies with the risk of recurrent cardiac events in postinfarction patients. Methods and Results —The study population consisted of 1150 patients with acute myocardial infarction. Levels of IgG and IgM aCL and aβ 2 GPI antibodies were determined on sera collected before hospital discharge. There were 131 recurrent cardiac events (nonfatal myocardial infarctions or cardiac deaths) over a mean follow-up period of 24.6 months. Patients with elevated IgG aCL antibodies had a higher event rate than patients with low levels ( P =0.05). Multivariate Cox analysis after adjustment for relevant clinical covariates showed that elevated levels of IgG aCL (hazard ratio=1.63; P =0.01) and low levels of IgM aCL (hazard ratio of 1.76; P =0.02) antibodies contribute independent risks for recurrent cardiac events. Patients with elevated IgG aCL and low IgM aCL antibody levels had a 3-fold higher risk of recurrent cardiac events than patients with low IgG aCL and elevated IgM aCL antibody levels ( P &lt;0.001). There was no significant association of the aβ 2 GPI antibodies with recurrent cardiac events. Conclusions —In postinfarction patients, elevated IgG aCL and low IgM aCL antibodies are independent risk factors for recurrent cardiac events. Patients with both elevated IgG aCL and low IgM aCL antibodies have the highest risk. These findings shed additional light on the mechanistic role of aCL antibodies in coronary artery disease in patients without autoimmune diseases.
A Multisite Assessment of the Quantitative Capabilities of the Xpert MTB/RIF Assay
Authors: Robert Blakemore, Pamela Nabeta, Amy L. Davidow, Viral Vadwai, Rasim Tahirli, Vanisha Munsamy, Mark Nicol, Martin Jones, David H. Persing, Doris Hillemann, Sabine Ruesch-Gerdes, Felicity Leisegang, Carlos Zamudio, Camilla Rodrigues, Catharina C. Boehme, Mark D. Perkins, David Alland
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: The Xpert MTB/RIF is an automated molecular test for Mycobacterium tuberculosis that estimates bacterial burden by measuring the threshold-cycle (Ct) of its M. tuberculosis–specific real-time polymerase chain reaction. Bacterial burden is an important biomarker for disease severity, infection control risk, and response to therapy.Objectives: Evaluate bacterial load quantitation by Xpert MTB/RIF compared with conventional quantitative methods.Methods: Xpert MTB/RIF results were compared with smear-microscopy, semiquantiative solid culture, and time-to-detection in liquid culture for 741 patients and 2,008 samples tested in a multisite clinical trial. An internal control real-time polymerase chain reaction was evaluated for its ability to identify inaccurate quantitative Xpert MTB/RIF results.Measurements and Main Results: Assays with an internal control Ct greater than 34 were likely to be inaccurately quantitated; this represented 15% of M. tuberculosis–positive tests. Excluding these, decreasing M. tuberculosis Ct was associated with increasing smear microscopy grade for smears of concentrated sputum pellets (rs = −0.77) and directly from sputum (rs = −0.71). A Ct cutoff of approximately 27.7 best predicted smear-positive status. The association between M. tuberculosis Ct and time-to-detection in liquid culture (rs = 0.68) and semiquantitative colony counts (rs = −0.56) was weaker than smear. Tests of paired same-patient sputum showed that high-viscosity sputum samples contained ×32 more M. tuberculosis than nonviscous samples. Comparisons between the grade of the acid-fast bacilli smear and Xpert MTB/RIF quantitative data across study sites enabled us to identify a site outlier in microscopy.Conclusions: Xpert MTB/RIF quantitation offers a new, standardized approach to measuring bacterial burden in the sputum of patients with tuberculosis.
Familial hyperkeratosis lenticularis perstans associated with tumours of the skin
Authors: G. W. BEVERIDGE, A. O. LANGLANDS
Journal: British Journal of Dermatology (1973)

A pedigree from a family with hyperkeratosis lenticularis perstans which shows a pattern of dominant inheritance is presented. This would appear to be the second occasion in which this condition has been shown to have a genetic basis. This family in addition shows a high incidence of cutaneous carcinomata, not arising in the keratosis. The possible significance of the association is discussed.
Interactions between insulin-like growth factor-I (IGF-I) and the renin-angiotensin system in follicular growth and ovulation.
Authors: Y Yoshimura, N Aoki, K Sueoka, T Miyazaki, N Kuji, M Tanaka, T Kobayashi
Journal: Journal of Clinical Investigation (1996)

The interactions between insulin-like growth factor-I (IGF-I) and the renin-angiotensin system (RAS) in follicular growth and ovulation were studied with the use of an isolated perfused rabbit ovary preparation. Ovulation failed to occur in either control ovaries or the experimental ovaries perfused with IGF-I in a concentration of 1, 10, or 100 ng/ml in the absence of gonadotropin. Exposure to IGF-I stimulated the secretion rate of angiotensin II-like immunoreactivity (Ang II-IR) in perfused rabbit ovaries in a dose-dependent manner. The percent increase in follicle diameter in ovaries perfused with IGF-I for 12 h was significantly correlated with the secretion rate of Ang II-IR at 12 h after exposure to IGF-I. The addition of IGFBP-3 to the perfusate did not induce ovulation in the absence of gonadotropin, but exposure to IGFBP-3 inhibited hCG-induced ovulation in a dose-dependent manner. In addition, IGFBP-3 significantly reduced the ovarian secretion rate of Ang II-IR and prostaglandins stimulated by hCG administration. Intrafollicular plasminogen activator (PA) activity significantly increased within 4 h after exposure to 100 ng/ml of IGF-I, compared with that in control ovaries perfused with medium alone. The concomitant addition of IGFBP-3 to the perfusate significantly reduced the IGF-I-stimulated PA activity in the preovulatory follicles at 4, 6, and 8 h after exposure to IGF-I. However, IGFBP-3 alone affected neither the ovarian secretion rate of Ang II-IR nor intrafollicular PA activity. Exposure to streptokinase, an exogenous PA, in vitro stimulated both follicular growth and the intrafollicular Ang II-IR content. In conclusion, IGF-I enhances both ovarian Ang II production and follicular development by stimulating intrafollicular PA activity.
Endothelin B Receptor Blockade Inhibits Dynamics of Cell Interactions and Communications in Melanoma Cell Progression
Authors: Anna Bagnato, Laura Rosanò, Francesca Spinella, Valeriana Di Castro, Raffaele Tecce, Pier Giorgio Natali
Journal: Cancer Research (2004)

Phenotypic and genotypic analyses of cutaneous melanoma have identified the endothelin B receptor (ET(B)R) as tumor progression marker, thus representing a potential therapeutic target. Here, we demonstrate that activation of ET(B)R by endothelin-1 (ET-1) and ET-3 leads to loss of expression of the cell adhesion molecule E-cadherin and associated catenin proteins and gain of N-cadherin expression. Exposure of melanoma cells to ET-1 leads to a 60% inhibition in intercellular communication by inducing phosphorylation of gap junctional protein connexin 43. Additionally, activation of the ET(B)R pathway increases alpha(v)beta(3) and alpha(2)beta(1) integrin expression and matrix metalloproteinase (MMP)-2 and MMP-9, membrane type-1-MMP activation, and tissue inhibitor MMP-2 secretion. The ET(B)R pathway results into the downstream activation of focal adhesion kinase and extracellular signal-regulated kinase 1/2 signaling pathways, which lead to enhanced cell proliferation, adhesion, migration, and MMP-dependent invasion. The small molecule A-192621, an orally bioavailable nonpeptide ET(B)R antagonist, significantly inhibits melanoma growth in nude mice. These findings demonstrate that ET-1 and ET-3 through ET(B)R activation trigger signaling pathways involved in events associated with disruption of normal host-tumor interactions and progression of cutaneous melanoma. Pharmacological interruption of ET(B)R signaling may represent a novel therapeutic strategy in the treatment of this malignancy.
Proliferating cell nuclear antigen in developing and adult rat cardiac muscle cells.
Authors: T A Marino, S Haldar, E C Williamson, K Beaverson, R A Walter, D R Marino, C Beatty, K E Lipson
Journal: Circulation Research (1991)

During early development, rat cardiac muscle cells actively proliferate. Shortly after birth, division of cardiac muscle cells ceases, whereas DNA synthesis continues for approximately 2 weeks at a progressively diminishing rate. Little DNA synthesis or cell division occurs in adult cardiocytes. Thus, developing cardiac muscle cells are an ideal system in which to examine the expression of cell cycle-regulated genes during development. We chose to examine proliferating cell nuclear antigen (PCNA), a gene expressed at the G1/S phase boundary of the cell cycle. Northern blots of RNA from cardiac muscle cells from 18-day-old rat fetuses and from day 0, 5, and 14 neonatal as well as adult rat hearts revealed that the PCNA mRNA was found in cardiac muscle cells from all ages. However, because it was possible that this was a result of fibroblast PCNA gene expression, we used reverse transcription followed by polymerase chain reaction to see if it was possible to detect the message for PCNA in cardiac muscle cells from all ages. Because of the great sensitivity of this technique, RNA was recovered from 25 isolated adult cardiac muscle cells. Polymerase chain reaction amplification products for PCNA produced from the RNA isolated from these cells conclusively demonstrated that mRNA for this gene, which normally is associated with proliferating cells, is expressed in adult cardiac muscle cells that no longer divide. Furthermore, Western blot analysis demonstrated that the PCNA protein was found only in embryonic and neonatal cells and not in adult rat cardiac muscle cells. Therefore, it might be inferred from these data that PCNA might be regulated at the posttranscriptional level in adult cardiac muscle cells.