tbuckley/cabot-search huggingface dataset:
To feed or not to feed?
Authors: Amy Davis, Lauren Ramsay
Journal: BMJ (2015)

Is it safe to use this nasogastric tube for enteral nutrition (fig 1⇓)?



No. Although the tip of the nasogastric tube is below the left hemidiaphragm, it follows the course of the left main bronchus and does not bisect the carina. The tip of the nasogastric tube is in …
Carcinoma of the Prostate: The Therapeutic Dilemma
Authors: D F Paulson
Journal: Annual Review of Medicine (1984)

The management of prostatic carcinoma remains confusing; however, recent studies indicate that treatment selection should be based upon the anatomic extent of disease. Disease that is confined within the anatomic limits of the prostate is best treated by surgically removing the gland. Disease that extends outside of the anatomic confines of the prostate is managed with difficulty and the optimum treatment is as yet undetermined. Disease that is symptomatic and involves distant sites is apparently best treated initially by androgen deprivation and then by multiagent chemotherapy if this fails.
Chlormezanone in Anxiety : A Drug Rediscovered?
Authors: KARL RICKELS, JORGE A. PEREIRA-OGAN, W. GEORGE CASE, IRMA CSANALOSI, MERRILL J. MIRMAN, JULIET E. NATHANSON, LAWRENCE C. PARISH
Journal: American Journal of Psychiatry (1974)

The efficacy of chlormezanone, an infrequently prescribed minor tranquilizer, was tested in a six-week double-blind trial involving 154 anxious outpatients. The results showed that chlormezanone (800 mg./day) was significantly more effective than placebo and was equal in effectiveness to chlordiazepoxide (40 mg./day). Chlormezanone produced significantly more sedation and more side effects, but no more attrition, than chlordiazepoxide. Furtherstudies confirming these results could establish chlormezanone as a useful antianxiety agent.
The effect of compliance with treatment on survival among patients with hematologic malignancies.
Authors: J L Richardson, D R Shelton, M Krailo, A M Levine
Journal: Journal of Clinical Oncology (1990)

Ninety-four newly diagnosed patients with hematologic malignancies were monitored for compliance with oral medication and scheduled clinic appointments over a 6-month treatment period. They were assigned at entry either to a control condition or an intervention condition designed to improve compliance. Compliance with medication was assessed objectively with serial serum drug and metabolite levels, as well as with self-report indices obtained on a monthly basis. Medical records were abstracted to obtain data on the number of appointments kept, treatment given, disease characteristics, and survival. On univariate analyses using the log-rank test, five variables were found to be significantly related to survival. These included compliance with allopurinol (probably acting as a surrogate for self-medication with other chemotherapeutic agents) (P = .007), control versus educational program cohort (P less than .001), disease severity (P = .009), Karnofsky at diagnosis (P = .011), sex (P = .084), and clinic appointments kept (P = .043). In hierarchical proportional hazards models, the following variables were associated with decreased risk of death: disease severity (P less than .025), keeping over 60% of appointments (P less than .05), allopurinol/oxipurinol compliance (P less than .01), and educational program cohort (P less than .05). After controlling for all other variables, three variables were associated with increased survival: high disease severity (relative risk [RR] = 2.48), high compliance with allopurinol (RR = .45), and educational program cohort (RR = .39). We conclude that compliance with oral medication has a significant effect on patient survival. In addition, the use of special educational and supportive programs designed to improve patient compliance are associated with significant prolongation of patient survival due to, as well as independent of their effects on compliance.
Long-Term Prognosis of Early Repolarization With J-Wave and QRS Slur Patterns on the Resting Electrocardiogram
Authors: Vedant S. Pargaonkar, Marco V. Perez, Akash Jindal, Maya B. Mathur, Jonathan Myers, Victor F. Froelicher
Journal: Annals of Internal Medicine (2015)

The prognostic value of early repolarization with J waves and QRS slurs remains controversial. Although these findings are more prevalent in patients with idiopathic ventricular fibrillation, their ability to predict cardiovascular death has varied across studies.To test the hypothesis that J waves and QRS slurs on electrocardiograms (ECGs) are associated with increased risk for cardiovascular death.Retrospective cohort.Veterans Affairs Palo Alto Health Care System.Veterans younger than 56 years who had resting 12-lead electrocardiography, 90.5% of whom were men.Electrocardiograms were manually measured and visually coded using criteria of 0.1 mV or greater in at least 2 contiguous leads. J waves were measured at the peak of an upward deflection or notch at the end of QRS, and QRS slurs were measured at the top of conduction delay on the QRS downstroke. Absolute risk differences at 10 years were calculated to study the associations between J waves or QRS slurs and the primary outcome of cardiovascular death.Over a median follow-up of 17.5 years, 859 cardiovascular deaths occurred. Of 20 661 ECGs, 4219 (20%) had J waves or QRS slurs in the inferior and/or lateral territories; of these, 3318 (78.6%) had J waves or QRS slurs in inferior leads and 1701 (40.3%) in lateral leads. The upper bound of differences in risk for cardiovascular death from any of the J-wave or QRS slur patterns suggests that an increased risk can be safely ruled out (inferior, -0.77% [95% CI, -1.27% to -0.27%]; lateral, -1.07% [CI, -1.72% to -0.43%]).The study consisted of predominantly men, and deaths could be classified as cardiovascular but not arrhythmic.J waves and QRS slurs did not exhibit a clinically meaningful increased risk for cardiovascular death in long-term follow-up.None.
In Vivo Diagnostic and Therapeutic Uses of Monoclonal Antibodies in Cardiology
Authors: E Haber
Journal: Annual Review of Medicine (1986)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
A Prognostic Index for Locoregional Recurrence (Lrr) After Neoadjuvant Chemotherapy (Nac)
Authors: C. Herrero-Vicent, A. Guerrero, J. Gavila, F. Gozalbo, J. Giménez, J.L. Guinot, M.R. Chilet, M. Serrano, A. Hernández, M.Á. Climent, V. Guillem Porta, A. Ruiz
Journal: Annals of Oncology (2014)
Hepatocyte Nuclear Factor 1β–Associated Kidney Disease
Authors: Jacobien C. Verhave, Anneke P. Bech, Jack F.M. Wetzels, Tom Nijenhuis
Journal: Journal of the American Society of Nephrology (2015)

Hepatocyte nuclear factor 1β (HNF1β)–associated disease is a recently recognized clinical entity with a variable multisystem phenotype. Early reports described an association between HNF1B mutations and maturity-onset diabetes of the young. These patients often presented with renal cysts and renal function decline that preceded the diabetes, hence it was initially referred to as renal cysts and diabetes syndrome. However, it is now evident that many more symptoms occur, and diabetes and renal cysts are not always present. The multisystem phenotype is probably attributable to functional promiscuity of the HNF1β transcription factor, involved in the development of the kidney, urogenital tract, pancreas, liver, brain, and parathyroid gland. Nephrologists might diagnose HNF1β-associated kidney disease in patients referred with a suspected diagnosis of autosomal dominant polycystic kidney disease, medullary cystic kidney disease, diabetic nephropathy, or CKD of unknown cause. Associated renal or extrarenal symptoms should alert the nephrologist to HNF1β-associated kidney disease. A considerable proportion of these patients display hypomagnesemia, which sometimes mimics Gitelman syndrome. Other signs include early onset diabetes, gout and hyperparathyroidism, elevated liver enzymes, and congenital anomalies of the urogenital tract. Because many cases of this disease are probably undiagnosed, this review emphasizes the clinical manifestations of HNF1β-associated disease for the nephrologist.
Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses
Authors: Yu Sawada, Tetsuya Honda, Sho Hanakawa, Satoshi Nakamizo, Teruasa Murata, Yuri Ueharaguchi-Tanada, Sachiko Ono, Wataru Amano, Saeko Nakajima, Gyohei Egawa, Hideaki Tanizaki, Atsushi Otsuka, Akihiko Kitoh, Teruki Dainichi, Narihito Ogawa, Yuichi Kobayashi, Takehiko Yokomizo, Makoto Arita, Motonobu Nakamura, Yoshiki Miyachi, Kenji Kabashima
Journal: The Journal of Experimental Medicine (2015)

Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade.
Withdrawn: Budesonide-loaded enzyme- and pH-sensitive polymeric nanoparticles for the treatment of colitis
Authors: Muhammad Naeem, Jin-Wook Yoo
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice
Authors: Anne K McGavigan, Darline Garibay, Zachariah M Henseler, Jack Chen, Ahmed Bettaieb, Fawaz G Haj, Ruth E Ley, Michael L Chouinard, Bethany P Cummings
Journal: Gut (2015)

Vertical sleeve gastrectomy (VSG) produces high rates of type 2 diabetes remission; however, the mechanisms responsible remain incompletely defined. VSG increases circulating bile acid concentrations and bile acid signalling through TGR5 improves glucose homeostasis. Therefore, we investigated the role of TGR5 signalling in mediating the glucoregulatory benefits of VSG.VSG or sham surgery was performed in high-fat-fed male Tgr5+/+ (wild type) and Tgr5-/- (knockout) littermates. Sham-operated mice were fed ad libitum or food restricted to match their body weight to VSG-operated mice. Body weight, food intake, energy expenditure, insulin signalling and circulating bile acid profiles were measured and oral glucose tolerance testing, islet immunohistochemistry and gut microbial profiling were performed.VSG decreased food intake and body weight, increased energy expenditure and circulating bile acid concentrations, improved fasting glycaemia, glucose tolerance and glucose-stimulated insulin secretion, enhanced nutrient-stimulated glucagon-like peptide 1 secretion and produced favourable shifts in gut microbial populations in both genotypes. However, the body weight-independent improvements in fasting glycaemia, glucose tolerance, hepatic insulin signalling, hepatic inflammation and islet morphology after VSG were attenuated in Tgr5-/- relative to Tgr5+/+ mice. Furthermore, VSG produced metabolically favourable alterations in circulating bile acid profiles that were blunted in Tgr5-/- relative to Tgr5+/+ mice. TGR5-dependent regulation of hepatic Cyp8b1 expression may have contributed to TGR5-mediated shifts in the circulating bile acid pool after VSG.These results suggest that TGR5 contributes to the glucoregulatory benefits of VSG surgery by promoting metabolically favourable shifts in the circulating bile acid pool.
Summative assessment will protect patients from incompetent GPs
Authors: J. Hayden
Journal: BMJ (1995)

EDITOR,--There seems to be some misunderstanding by the general practitioner registrars' subcommittee of the General Medical Services Committee in relation to summative assessment.1

Firstly, the registrars express concerns about the validity of summative assessment. The work that has been done by the United Kingdom conference of postgraduate advisers in general practice has ensured that the assessment has a high validity; indeed, general practice …
Agonist anti-4-1BB plus neutralizing anti-CTLA-4 or -PD-L1 synergize to promote tumor regression by rescuing dying dysfunctional CD8+ T cells within the tumor microenvironment
Authors: Brendan Horton, Jason B Williams, Stefani Spranger, Thomas F Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Tumors can be broadly placed into two categories: those that are T cell-inflamed and those that are not, with T cell-inflamed tumors having specific chemokine and type I interferon gene expression signatures as well as CD8+ tumor-infiltrating T cells (TIL). The fact that these T
P32 Gut sterilisation with norfloxacin modulates cerebral inflammation in cirrhosis and prevents deterioration in brain oedema and delays coma in cirrhotic rats
Authors: N Shah, D Dhar, R P Mookerjee, N A Davies, R Jalan
Journal: Gut (2010)

Introduction  In a bile duct ligated (BDL) rodent model of cirrhosis, superimposed infection/inflammation leads to multiorgan failure including cerebral inflammation, worsening oedema and coma. The mechanism of why cirrhotic animals are predisposed to the effect of LPS is not clear. Toll like receptors, the ubiquitous receptors for bacteria trigger an inflammatory cascade through NFkB. We hypothesised that endotoxemia in cirrhosis primes the brain leading to an activation of TLR4 pathway which can be modulated by selective gut decontamination.  Aim  The aims of the study were to determine whether (1) cirrhosis is associated with altered expression of TLR4 (endotoxin receptor), NFkB and cytokines in the brain and whether (2) selective decontamination of gut with norfloxacin would attenuate TLR4 expression and therefore protect against the development of accelerated brain oedema following LPS administration.  Method  Six groups of Sprague–Dawley rats were studied (n=6 each). Animals underwent sham operation or bile-duct ligation (BDL) and were studied 4 weeks later. The animals were studied at coma stages after administration of LPS (1 mg/Kg) or vehicle. Study groups: Sham operated, Sham-operated+LPS; BDL (4 weeks), BDL+LPS; BDL+norfloxacin and BDL+LPS (norfloxacin 20 mg/kg daily for 10 days; PO). Ammonia (measured spectrophotometrically), brain cytokines (ELISA) were measured. Protein expression of Brain TLR4 and NFkBp65 was assessed with Western blot and the frontal cortex for brain water (dry weight method).  Results  TLR4 and NFkBp65 protein expression was significantly higher in BDL rats (p=0.04 and p=0.03), this increased further on administration of LPS (p=0.02 and p=0.01) respectively. Norfloxacin reduced the expression of TLR4 and NFkBp65 to sham levels (p=0.03, p=0.02) respectively. Selective decontamination of gut with norfloxacin led to a reduction in ammonia (p=0.04, p=0.01), brain water (p=0.04, p=0.04) and brain TNF (p=0.02, p=0.02) in BDL and BDL rats treated with LPS respectively. Pre-treatment of the BDL animals with norfloxacin prior to administration of LPS significantly delayed occurrence of coma and improved survival (p  Conclusion  Our data provide strong evidence indicating an important pathogenic role of TLR4 in mediating susceptibility of cirrhotics to worsening coma following an infection/inflammation. Selective gut decontamination with norfloxacin attenuates the TLR4 expression thereby modulating the inflammatory milieu in the brain, delays coma and improves survival in cirrhotic animals administered LPS. Selective inhibition of TLR4 and/or selective gut decontamination may be therapeutic targets in hepatic encephalopathy.
Abstract 1370: Activin receptor-like kinase 1 ligand trap reduces microvascular density and improves chemotherapy efficiency to various solid tumors
Authors: Lukas JAC Hawinkels, Amaya Garcia de Vinuesa, Madelon Paauwe, Marianna Kruithof-de Julio, Renier Heijkants, Marie-Jose Goumans, Timo ten Hagen, Peter ten Dijke
Journal: Cancer Research (2015)

Abstract Anti-angiogenic therapy, mostly targeting vascular endothelial growth factor (VEGF), has been clinical applied in cancer patients for the last decade. However, often resistance to anti-VEGF therapy and/or no significant benefit as monotherapeutic agent is often observed. Therefore, new anti-angiogenic strategies are needed. In this study we analyzed the potential anti-angiogenic effects of activin-receptor-like kinase (ALK)1-Fc protein. ALK1-Fc sequesters bone morphogenetic protein (BMP)-9 and -10 and prevents binding of these ligands to endothelial ALK1, which controls angiogenesis. Treatment of mice with breast cancer, head and neck cancer, or melanomas strongly decreased the tumors’ microvascular density, but this effect was not accompanied by a reduction in tumor volume. In contrast to anti-VEGF therapy, we observed decreased hypoxia, and increased staining for pericytes, consistent with the notion that ALK1-Fc may have induced a normalization of the remaining tumor vessels. Next we found that combined regimen of ALK1-Fc with chemotherapy inhibited tumor growth in the breast- and head and neck cancer models more efficiently than chemotherapy alone. Our results provide strong rational to explore combined targeting of ALK1 with chemotherapy in a clinical setting, especially in the ongoing phase-II clinical trials with ALK1-Fc. Citation Format: Lukas JAC Hawinkels, Amaya Garcia de Vinuesa, Madelon Paauwe, Marianna Kruithof-de Julio, Renier Heijkants, Marie-Jose Goumans, Timo ten Hagen, Peter ten Dijke. Activin receptor-like kinase 1 ligand trap reduces microvascular density and improves chemotherapy efficiency to various solid tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1370. doi:10.1158/1538-7445.AM2015-1370
Germline Findings in Tumor-Only Sequencing: Points to Consider for Clinicians and Laboratories: Table 1.
Authors: Victoria M. Raymond, Stacy W. Gray, Sameek Roychowdhury, Steve Joffe, Arul M. Chinnaiyan, D. Williams Parsons, Sharon E. Plon
Journal: JNCI Journal of the National Cancer Institute (2015)

Precision oncology holds great potential to improve patient therapies and outcomes. Tumor sequencing is rapidly moving into clinical care as our understanding of the cancer genome and the availability of targeted therapies increase. Analysis of the cancer genome is most informative when paired with germline genomic DNA to delineate inherited and somatic variants. Although tumor-only analysis remains the most common methodology for numerous reasons, it holds the potential to identify clinically significant germline variants. Here, we provide anticipatory guidance and points to consider for laboratories and clinicians regarding the potential for germline findings in tumor sequencing.
Thiazolidinedione Use, Fluid Retention, and Congestive Heart Failure
Authors: Richard W. Nesto, David Bell, Robert O. Bonow, Vivian Fonseca, Scott M. Grundy, Edward S. Horton, Martin Le Winter, Daniel Porte, Clay F. Semenkovich, Sidney Smith, Lawrence H. Young, Richard Kahn
Journal: Diabetes Care (2004)

Diabetes is a chronic, progressively worsening disease associated with a variety of microvascular and macrovascular complications. Cardiovascular disease (CVD) is the main cause of death in these patients (1,2). During the past decade, numerous drugs have been introduced for the treatment of type 2 diabetes that, used in monotherapy or in combination therapy, are effective in lowering blood glucose to achieve glycemic goals and in reducing diabetes-related end-organ disease.

Two such drugs, rosiglitazone and pioglitazone, belong to the class called thiazolidinediones (TZDs) (3). Troglitazone, the first agent of this class to be approved, was effective in controlling glycemia but was removed from the market because of serious liver toxicity. Both rosiglitazone and pioglitazone are indicated either as monotherapy or in combination with a sulfonylurea, metformin, or insulin when diet, exercise, and a single agent do not result in adequate glycemic control (4) (package insert Avandia [rosiglitazone maleate; GlaxoSmithKline] and Actos (5) [pioglitazone hydrochloride; Takeda Pharmaceuticals]). In addition to lowering blood glucose, both drugs may benefit cardiovascular parameters, such as lipids, blood pressure, inflammatory biomarkers, endothelial function, and fibrinolytic status (6,7).

These beneficial effects of TZDs on glycemia and cardiovascular risk factors have made them attractive agents in patients with type 2 diabetes who are at high risk for CVD. There is a growing recognition, however, that edema can occur in patients treated with either drug. Because people with diabetes are at increased risk for CVD and many have preexisting heart disease, the edema that sometimes accompanies the use of a TZD can be cause for concern, as it may be a harbinger or sign of congestive heart failure (CHF). An analysis of Medicare beneficiaries hospitalized with the diagnosis of diabetes and CHF indicated that the number of these patients discharged on TZDs had increased from …