tbuckley/cabot-search huggingface dataset:
C-reactive protein: a predictive factor and marker of inflammation in inflammatory bowel disease. Results from a prospective population-based study
Authors: M Henriksen, J Jahnsen, I Lygren, N Stray, J Sauar, M H Vatn, B Moum
Journal: Gut (2008)

<h3>Background and aims:</h3> C-reactive protein (CRP) levels are often used in the follow-up of patients with inflammatory bowel disease (IBD). The aims of this study were to establish the relationship of CRP levels to disease extent in patients with ulcerative colitis and to phenotype in patients with Crohn's disease, and to investigate the predictive value of CRP levels for disease outcome. <h3>Methods:</h3> CRP was measured at diagnosis and after 1 and 5 years in patients diagnosed with IBD in south-eastern Norway. After 5 years, 454 patients with ulcerative colitis and 200 with Crohn's disease were alive and provided sufficient data for analysis. <h3>Results:</h3> Patients with Crohn's disease had a stronger CRP response than did those with ulcerative colitis. In patients with ulcerative colitis, CRP levels at diagnosis increased with increasing extent of disease. No differences in CRP levels at diagnosis were found between subgroups of patients with Crohn's disease as defined according to the Vienna classification. In patients with ulcerative colitis with extensive colitis, CRP levels above 23 mg/l at diagnosis predicted an increased risk of surgery (odds ratio (OR) 4.8, 95% confidence interval (CI) 1.5 to 15.1, p = 0.02). In patients with ulcerative colitis, CRP levels above 10 mg/l after 1 year predicted an increased risk of surgery during the subsequent 4 years (OR 3.0, 95% CI 1.1 to 7.8, p = 0.02). A significant association between CRP levels at diagnosis and risk of surgery was found in patients with Crohn's disease and terminal ileitis (L1), and the risk increased when CRP levels were above 53 mg/l in this subgroup (OR 6.0, 95% CI 1.1 to 31.9, p = 0.03). <h3>Conclusions:</h3> CRP levels at diagnosis were related to the extent of disease in patients with ulcerative colitis. Phenotype had no influence on CRP levels in patients with Crohn's disease. CRP is a predictor of surgery in subgroups of patients with either ulcerative colitis or Crohn's disease.
Anemia of Chronic Disease
Authors: Guenter Weiss, Lawrence T. Goodnough
Journal: New England Journal of Medicine (2005)

New therapeutic strategies have emerged along with our understanding that disturbances of iron homeostasis, impaired proliferation of erythroid progenitor cells, and blunted erythropoietin response occur in anemia of chronic disease. This review discusses advances in our knowledge of the causes and management of the condition.
Impact of Modafinil on Prefrontal Executive Function in Schizophrenia
Authors: Michael Hunter
Journal: American Journal of Psychiatry (2006)

Objective: The purpose of this study was to investigate the acute effects of modafinil on prefrontal activation and cognitive control of motor activity in people with schizophrenia and prominent negative symptoms. Method: In a crossover design, 12 subjects with schizophrenia were studied twice, receiving either modafinil or placebo prior to functional magnetic resonance imaging (fMRI). Inside the scanner, they performed a task probing cognitive control that required deliberate variation of motor activity in time. Results: Modafinil administration was associated with significantly greater activation of the dorsolateral prefrontal cortex during fMRI. Its physiological and behavioral effects were correlated. This was most evident in individuals with worse baseline executive function. Focal response to modafinil in the left dorsolateral prefrontal cortex and baseline letter fluency scores predicted most of the variance in the drug's effect on cognitive control. Conclusions: Modafinil did not improve cognitive control in all schizophrenia patients. Increased activation in the dorsolateral prefrontal cortex and in neuropsychological performance were observed in patients with suboptimal baseline function.
Association of 1800 cGy cranial irradiation with intellectual function in children with acute lymphoblastic leukaemia
Authors: M Jankovic, G Masera, P Brouwers, M.G Valsecchi, A.V Veldhuizen, A Kingma, J Huisman, R Kamphuis, A Kingma, W Mor, J.V Dongen-Melman, L Ferronato, A Mancini, W Mor, Jj Spinetta, None Giuseppe Masera for ISPACC
Journal: The Lancet (1994)
Test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours
Authors: H. A. Pattenden, M. Leung, E. Beddow, M. Dusmet, A. G. Nicholson, M. Shackcloth, S. Mohamed, A. Darr, B. Naidu, S. Iyer, A. Marchbank, A. Greenwood, D. West, F. Granato, A. Kirk, P. Ariyaratnam, M. Loubani, E. Lim
Journal: Thorax (2014)

Positron emission tomography-CT (PET-CT) is one of the initial mediastinal staging modality for non-small cell lung cancer; however, the clinical utility in carcinoid tumours is uncertain. We sought to determine the test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours. We collated data from seven institutions, performing a retrospective search on pathological databases for a consecutive series of patients who underwent thoracic surgery (with lymph nodal dissection) for carcinoid tumours with preoperative PET-CT staging. PET-CT results were compared with the reference standard of pathologic results obtained from lymph node dissection and test performance reported using sensitivity and specificity. From November 1999 to January 2013, 247 patients from seven institutions underwent surgery for carcinoid tumours with a corresponding preoperative PET-CT scan. The mean age of the patients was 61 (SD 15, range 73) and 84 were male patients (34%). The pathologic subtype was typical carcinoid in 217 patients (88%) and atypical carcinoid in 30 patients (12%). Results from lymph node dissection were obtained in 207 patients. The calculated sensitivity and specificity of PET-CT to identify mediastinal lymph node disease was 33% (95% CI 4% to 78%) and 94% (95% CI 89% to 97%), respectively. Our results indicate that PET-CT has a poor sensitivity but good specificity to detect the presence of mediastinal lymph node metastases in pulmonary carcinoid tumours. Mediastinal lymph node metastases cannot be ruled out with negative PET-CT uptake, and if the absence of mediastinal lymph node disease is a prerequisite for directing management, tissue sampling should be undertaken.
Deficits in Sialylation Impair Podocyte Maturation
Authors: Birgit Weinhold, Melanie Sellmeier, Wiebke Schaper, Linda Blume, Brigitte Philippens, Elina Kats, Ulrike Bernard, Sebastian P. Galuska, Hildegard Geyer, Rudolf Geyer, Kirstin Worthmann, Mario Schiffer, Stephanie Groos, Rita Gerardy-Schahn, Anja K. Münster-Kühnel
Journal: Journal of the American Society of Nephrology (2012)

The role of sialylation in kidney biology is not fully understood. The synthesis of sialoglycoconjugates, which form the outermost structures of animal cells, requires CMP-sialic acid, which is a product of the nuclear enzyme CMAS. We used a knock-in strategy to create a mouse with point mutations in the canonical nuclear localization signal of CMAS, which relocated the enzyme to the cytoplasm of transfected cells without affecting its activity. Although insufficient to prevent nuclear entry in mice, the mutation led to a drastically reduced concentration of nuclear-expressed enzyme. Mice homozygous for the mutation died from kidney failure within 72 hours after birth. The Cmasnls mouse exhibited podocyte foot process effacement, absence of slit diaphragms, and massive proteinuria, recapitulating features of nephrin-knockout mice and of patients with Finnish-type congenital nephrotic syndrome. Although the Cmasnls mouse displayed normal sialylation in all organs including kidney, a critical shortage of CMP-sialic acid prevented sialylation of nephrin and podocalyxin in the maturing podocyte where it is required during the formation of foot processes. Accordingly, the sialylation defects progressed with time and paralleled the morphologic changes. In summary, sialylation is critical during the development of the glomerular filtration barrier and required for the proper function of nephrin. Whether altered sialylation impairs nephrin function in human disease requires further study.
Risk Factors for Pulmonary Tuberculosis in Bone Marrow Transplant Recipients
Authors: MARY S. M. IP, K. Y. YUEN, PATRICK C. Y. WOO, W. K. LUK, KENNETH W. T. TSANG, W. K. LAM, RAYMOND H. S. LIANG
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Little is known about the profile of infection with Mycobacterium tuberculosis in bone marrow transplant (BMT) recipients. Of five BMT series with a total of more than 5,000 patients, only 10 cases of M. tuberculosis infection were described, with an overall incidence of 0.19%. We have conducted a prospective evaluation of 183 consecutive BMT recipients, and 10 patients were found to develop pulmonary tuberculosis post-BMT, yielding an incidence of 5.5%. We described the clinical features of these 10 patients, and analyzed the risk factors for development of tuberculosis using age- and sex-matched case control subjects who did not develop the disease. The median age of the 10 patients who developed tuberculosis was 29 yr (range, 17 to 40 yr). The median time for onset of symptoms was 150 d (range, 23 to 550 d), mainly presenting with fever and cough, with infiltrates on chest radiograph. Respiratory tract specimens, mostly sputum, yielded positive smears for acid-fast bacilli in three and positive M. tuberculosis culture in eight, whereas lung tissue histology was the first diagnostic test in two patients. Treatment with standard antituberculosis drugs for a longer duration was highly effective, with no excessive side effects. Risk factors identified for development of tuberculosis included allogeneic BMT (p < 0.05, relative risk [RR] = 23.7), total body irradiation (p < 0.05, RR = 4.9), and chronic graft-versus-host disease (GVHD) (p < 0.05, RR = 3.6). It is postulated that chronic GVHD predisposed to development of tuberculosis mainly via disruption of host reconstitution of immune defenses against M. tuberculosis.
Use of Dr is perhaps even more confusing in Germany than UK
Authors: D. A Groneberg
Journal: BMJ (2001)

<h3>Abstract</h3> Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), became a pandemic in early 2020. Lateral flow immunoassays for antibody testing have been viewed as a cheap and rapidly deployable method for determining previous infection with SARS-CoV-2; however, these assays have shown unacceptably low sensitivity. We report on nine lateral flow immunoassays currently available and compare their titer sensitivity in serum to a best-practice enzyme-linked immunosorbent assay (ELISA) and viral neutralization assay. For a small group of PCR-positive, we found two lateral flow immunoassay devices with titer sensitivity roughly equal to the ELISA; these devices were positive for all PCR-positive patients harboring SARS-CoV-2 neutralizing antibodies. One of these devices was deployed in Northern Italy to test its sensitivity and specificity in a real-world clinical setting. Using the device with fingerstick blood on a cohort of 27 hospitalized PCR-positive patients and seven hospitalized controls, ROC curve analysis gave AUC values of 0.7646 for IgG. For comparison, this assay was also tested with saliva from the same patient population and showed reduced discrimination between cases and controls with AUC values of 0.6841 for IgG. Furthermore, during viral neutralization testing, one patient was discovered to harbor autoantibodies to ACE2, with implications for how immune responses are profiled. We show here through a proof-of-concept study that these lateral flow devices can be as analytically sensitive as ELISAs and adopted into hospital protocols; however, additional improvements to these devices remain necessary before their clinical deployment.
Long-term treatment of pulmonary hypertension with aerosolized iloprost
Authors: T. Saba, A.J. Peacock
Journal: European Respiratory Journal (2001)

To the Editor: 

We are concerned about the conclusions drawn by Macherndl et al. 1 which appear to contradict the findings of Hoeper et al. 2 last year. The authors report on the results of nebulized iloprost therapy in 12 subjects with a dose of 100–150 µg for 3–19 months, and conclude that “inhaled iloprost in addition to conventional therapy in the presently recommended dose of 100 µg·day−1 delivered in 8–10 two-hour portions is not an efficient vasodilator therapy in severe pulmonary hypertension.”

We agree with Galie 3 that uncontrolled trials can be misleading because of …
GPs should be freed up to make more endoscopy referrals, cancer charity says
Authors: A. O'Dowd
Journal: BMJ (2014)

General practitioners should be allowed more flexibility and freedom to refer patients for endoscopy investigations, a leading charity has said.

In a report published on 28 May Bowel Cancer UK called for existing national GP guidelines on referring urgent suspected bowel cancer cases to be “liberalised.”1

The current guidelines from the National Institute for Health and Care Excellence (NICE) are not working well enough, said the charity. It raised concerns about endoscopy services, such as patients having difficulty in qualifying for an urgent referral, having to wait too long, and experiencing varying quality in treatment.

Bowel cancer is diagnosed in more than 40 000 people every year …
Controversies in Treatment Deintensification of Human Papillomavirus–Associated Oropharyngeal Carcinomas: Should We, How Should We, and for Whom?
Authors: Harry Quon, Arlene A. Forastiere
Journal: Journal of Clinical Oncology (2013)

It has been little more than a decade since the recognition of the epidemiology, distinct molecular biology, and profile of risk factors, patient demographics, and tumor characteristics of human papillomavirus (HPV) ‐associated oropharyngeal squamous cell carcinoma (OPSCC). 1-3 From prospective and retrospective studies, we know that patients with locally advanced, stage III/IV, HPV-associated OPSCC who are treated with standard cisplatin-based concurrent chemoradiotherapy have significantly better overall survival and reduced risk of recurrence compared with patients with HPV-negative OPSCC. 4-6 More than 80% will likely be cured of their cancer. That said, it is also evident that a subset of patients demonstrate an aggressive phenotype with the development of distant spread and death as a result of their cancer. Given that the typical patient with HPV-associated OPSCC is younger (age 40 to 60 years) and without major comorbidities, increasing discussion has been focused on deintensification of treatmentinthehopesofminimizingtreatment-relatedmorbidity without compromising the current cure rates. In particular, attention has been focused on reducing the morbidity of severe late swallowing complications that result in the need for enteral nutritional support, because this has been shown to substantially affect patient quality of life. 7 Historically, typical rates of long-term gastrostomy-tube dependence were reported to be 15% to 20%. 8,9 However, with advances in radiationtechnology(suchasintensity-modulatedradiationtherapy), target delineation has become more complex, with steeper dose gradients and shifting of dose away from organs at risk, such that the current frequency of severe swallowing dysfunction needs to be reestablished. Nonetheless, maximizing quality of life by not overtreating patients is a uniformly supported goal. Deintensificationstrategieshavetodatebeenbasedonanunder
Lipid starvation and hypoxia synergistically activate ICAM1 and multiple genes in an Sp1-dependent manner to promote the growth of ovarian cancer
Authors: Shiro Koizume, Shin Ito, Yoshiyasu Nakamura, Mitsuyo Yoshihara, Mitsuko Furuya, Roppei Yamada, Etsuko Miyagi, Fumiki Hirahara, Yasuo Takano, Yohei Miyagi
Journal: Molecular Cancer (2015)

Elucidation of the molecular mechanisms by which cancer cells overcome hypoxia is potentially important for targeted therapy. Complexation of hypoxia-inducible factors (HIFs) with aryl hydrocarbon receptor nuclear translocators can enhance gene expression and initiate cellular responses to hypoxia. However, multiple molecular mechanisms may be required for cancer cells to adapt to diverse microenvironments. We previously demonstrated that a physical interaction between the ubiquitously expressed transcription factor Sp1 and HIF2 is a major cause of FVII gene activation in poor prognostic ovarian clear cell carcinoma (CCC) cells under hypoxia. Furthermore, it was found that FVII activation is synergistically enhanced when serum-starved cells are cultured under hypoxic conditions. In this study, we investigated whether HIFs and transcription factor Sp1 cooperate to activate multiple genes in CCC cells under conditions of serum starvation and hypoxia (SSH) and then contribute to malignant phenotypes.To identify genes activated under hypoxic conditions in an Sp1-dependent manner, we first performed cDNA microarray analyses. We further investigated the molecular mechanisms of synergistic gene activations including the associated serum factors by various experiments such as real-time RT-PCR, western blotting and chromatin immunoprecipitation. The study was further extended to animal experiments to investigate how it contributes to CCC progression in vivo.ICAM1 is one such gene dramatically induced by SSH and is highly induced by SSH and its synergistic activation involves both the mTOR and autonomously activated TNFα-NFκB axes. We identified long chain fatty acids (LCFA) as a major class of lipids that is associated with albumin, a serum factor responsible for synergistic gene activation under SSH. Furthermore, we found that ICAM1 can be induced in vivo to promote tumor growth.Sp1 and HIFs collaborate to activate genes required for the adaptation of CCC cells to severe microenvironments, such as LCFA starvation and hypoxia. This study highlights the importance of transcriptional regulation under lipid starvation and hypoxia in the promotion of CCC tumor growth.
Treating Central Sleep Apnea in Heart Failure
Authors: Lyle J. Olson, Virend K. Somers
Journal: Circulation (2007)

recent enhanced appreciation of sleep-cardiovascular interactions, particularly in patients with congestive heart failure (CHF), has prompted careful consideration of the relevance of sleep-disordered breathing to CHF pathophysiology, progression, and treatment. 1Sleepdisordered breathing may be broadly classified as either obstructive sleep apnea (OSA) or central sleep apnea (CSA). 1 The former is characterized by repetitive collapse of the upper airway, whereas in patients with CHF, the latter is most often due to periodic alternation of diminished ventilatory drive and compensatory hyperventilation typical of Cheyne-Stokes respiration (Figure 1).CSA is likely a consequence rather than a cause of CHF.Although the mechanisms that underlie CSA/Cheyne-Stokes respiration in patients with CHF are not well understood, pulmonary congestion with increased lung J-receptor stimulation and greater chemosensitivity may play a role in the genesis of the periodic breathing that characterizes this disorder. 1,2 Article p 3173Of 5 million North Americans with CHF, an estimated 50% may have coexistent sleep apnea.Although the prevalence of OSA is much higher than CSA in the general population, 3 it appears that this relationship may be reversed among patients with systolic heart failure.Case series have reported frequencies of CSA exceeding 40% for stable, ambulatory patients with CHF in a ratio Ͼ2:1 relative to the frequency of OSA.Indeed, the frequency of OSA in these same series was similar to that observed in the general population, whereas the frequency of CSA was strikingly higher. 4,5Furthermore, in patients with CHF, CSA has been associated with increased morbidity and mortality, [5][6][7] increased neurohormonal activation, 1 increased ventricular arrhythmia, 8 decreased exercise capacity, 5,9 and more advanced New York Heart Association class. 5However, whether these associations merely reflect more advanced CHF or whether repetitive apneas with hypoxia and sympathetic neural activation 10 independently promote disease progression and adverse outcomes remains unknown.
4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone from Cigarette Smoke Stimulates Colon Cancer Growth via β-Adrenoceptors
Authors: William K.K. Wu, Helen P.S. Wong, Shi W. Luo, Kevin Chan, Fung Y. Huang, Marco K.C. Hui, Emily K.Y. Lam, Vivian Y. Shin, Yi N. Ye, Ying H. Yang, Chi H. Cho
Journal: Cancer Research (2005)

Cigarette smoking is a risk factor for colorectal cancer. It is suggested that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific nitrosamine, mediates the carcinogenic action of cigarette smoking by promoting cancer growth. In the present study, the proliferative response of a cultured colon cancer cell line HT-29 to NNK was determined. It was found that NNK dose-dependently stimulated HT-29 cell proliferation. In this regard, the stimulatory action of NNK was abolished by atenolol and ICI 118,551, a beta1- and beta2-selective antagonist, respectively. In addition, cell growth was stimulated by the nonselective adrenergic agonist, noradrenaline, and more effectively by the beta-selective agonist, isoproterenol. The second message cyclic AMP level for beta-adrenoceptor activation was elevated by isoproterenol and NNK treatment. These agents also up-regulated cyclooxygenase-2 expression, cytosolic phospholipase A2 expression, and prostaglandin E2 release. Beta2-adrenoceptor blockade with ICI 118,551, in contrast, significantly decreased cyclooxygenase-2 expression, cytosolic phospholipase A2 expression and prostaglandin E2 release induced by NNK and isoproterenol. To conclude, it is proposed that NNK stimulates HT-29 cell proliferation through beta-adrenoceptors, preferentially beta2 receptors. Activation of the beta-adrenoceptors, and the consequent cyclic AMP elevation coupled with the downstream arachidonic acid pathway, is perhaps an important mechanistic cascade in the promotion of colon cancer growth. These findings partly elucidate the carcinogenic actions of cigarette smoke and shed new light on the novel modulatory role of beta-adrenoceptors in the development of colon cancer.
Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone marrow depression
Authors: E. R. Broun
Journal: JAMA (1990)

Two patients with sideroblastic anemia secondary to zinc-induced copper deficiency absorbed excess zinc secondary to oral ingestion. The source of excess zinc was a zinc supplement in one case; in the other, ingested coins. In each case, the sideroblastic anemia was corrected promptly after removal of the source of excess zinc. These two cases emphasize the importance of recognizing this clinical entity, since the myelodysplastic features are completely reversible.