tbuckley/cabot-search huggingface dataset:
MicroRNAs in Vascular and Metabolic Disease
Authors: Anna Zampetaki, Manuel Mayr
Journal: Circulation Research (2012)

Recent findings demonstrated the importance of microRNAs (miRNAs) in the vasculature and the orchestration of lipid metabolism and glucose homeostasis. MiRNA networks represent an additional layer of regulation for gene expression that absorbs perturbations and ensures the robustness of biological systems. This function is very elegantly demonstrated in cholesterol metabolism where miRNAs reducing cellular cholesterol export are embedded in the very same genes that increase cholesterol synthesis. Often their alteration does not affect normal development but changes under stress conditions and in disease. A detailed understanding of the molecular and cellular mechanisms of miRNA-mediated effects on metabolism and vascular pathophysiology could pave the way for the development of novel diagnostic markers and therapeutic approaches. In the first part of this review, we summarize the role of miRNAs in vascular and metabolic diseases and explore potential confounding effects by platelet miRNAs in preclinical models of cardiovascular disease. In the second part, we discuss experimental strategies for miRNA target identification and the challenges in attributing miRNA effects to specific cell types and single targets.
Impact of familial amyloid associated polyneuropathy on duodenal endocrine cells.
Authors: M el-Salhy, O Suhr, R Stenling, E Wilander, L Grimelius
Journal: Gut (1994)

Duodenal endocrine cells in 11 patients with familial amyloid associated polyneuropathy (FAP) were compared with those in 12 healthy volunteers by means of immunohistochemistry and morphometry. The total endocrine cell content, determined by the argyrophilic reaction and chromogranin A immunoreactivity, was significantly reduced in FAP patients compared with controls. There was a significant reduction in the serotonin, cholecystokinin/gastrin, and secretin immunoreactive cell content. A decreased cell content was also noted for somatostatin and gastric inhibitory polypeptide immunoreactive cells but this was not statistically significant. Amyloid deposits were noted in seven of the 11 biopsy specimens from FAP patients, but otherwise the duodenum was histologically normal in both groups. The reduction in endocrine cell content was not correlated with the degree of amyloid deposit in the duodenum. These findings indicate that patients with FAP have reduced intestinal endocrine cells. This does not seem to be related to amyloid deposits in the mucosa or to villous or crypt abnormalities. The observed changes in endocrine cells may contribute to the development of intestinal motility dysfunction and maldigestion in these patients.
Wnt-5aoccludes Aβ oligomer-induced depression of glutamatergic transmission in hippocampal neurons
Authors: Waldo Cerpa, Ginny G Farías, Juan A Godoy, Marco Fuenzalida, Christian Bonansco, Nibaldo C Inestrosa
Journal: Molecular Neurodegeneration (2010)

Soluble amyloid-beta (Abeta;) oligomers have been recognized to be early and key intermediates in Alzheimer's disease (AD)-related synaptic dysfunction. Abeta oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. Wnt signaling plays an important role in neural development, including synaptic differentiation.We report here that the Wnt signaling activation prevents the synaptic damage triggered by Abeta oligomers. Electrophysiological analysis of Schaffer collaterals-CA1 glutamatergic synaptic transmission in hippocampal slices indicates that Wnt-5a increases the amplitude of field excitatory postsynaptic potentials (fEPSP) and both AMPA and NMDA components of the excitatory postsynaptic currents (EPSCs), without modifying the paired pulse facilitation (PPF). Conversely, in the presence of Abeta oligomers the fEPSP and EPSCs amplitude decreased without modification of the PPF, while the postsynaptic scaffold protein (PSD-95) decreased as well. Co-perfusion of hippocampal slices with Wnt-5a and Abeta oligomers occludes against the synaptic depression of EPSCs as well as the reduction of PSD-95 clusters induced by Abeta oligomers in neuronal cultures. Taken together these results indicate that Wnt-5a and Abeta oligomers inversely modulate postsynaptic components.These results indicate that post-synaptic damage induced by Abeta oligomers in hippocampal neurons is prevented by non-canonical Wnt pathway activation.
Traumatic occlusion of the external iliac artery in a racing cyclist: a cause of ill defined leg pain.
Authors: A J Taylor, W G Tennant, M E Batt, W A Wallace
Journal: British Journal of Sports Medicine (1997)

Stenosis of the external iliac artery in healthy athletes, although uncommon, has been reported in competition cyclists. A case of a racing cyclist whose chronic vague leg symptoms were incorrectly attributed to L4/5 nerve root irritation is reported. This highlights the importance of clinical vascular testing when assessing ill defined leg pain. The role of trauma as a causative factor in this condition has not been previously documented.
Genetic risk for colitis-associated colorectal cancer
Authors: E. H Warren
Journal: Gut (2009)

The development of colorectal cancer (CRC) is arguably the most feared complication of ulcerative colitis. Clinical variables correlated with the development of CRC in patients with ulcerative colitis include age at onset, duration and geographical extent of disease, and concomitant primary sclerosing cholangitis (PSC). Patients with ulcerative colitis and with extensive duration of disease or pancolitis have a cumulative lifetime risk of CRC that exceeds 30%.1 Although the pathogenesis of CRC that develops in patients with ulcerative colitis is poorly understood, several studies have identified molecular features that distinguish CRC associated with ulcerative colitis from sporadic CRC.2 3 4 5 CRC that develops in patients with ulcerative colitis is most common in the rectum and sigmoid colon, almost always occurs in areas involved by chronic inflammation, and is more frequently characterised by multiple synchronous tumours than is sporadic CRC.6 It is generally preceded by dysplasia, which therefore provides cogent rationale for colonoscopic surveillance for CRC in patients with ulcerative colitis, particularly those with pancolitis and extended duration of disease.

Although a large number of germline and somatic genetic lesions have been associated with a predisposition to the development of CRC, little is known about the extent to which genetic factors may influence the risk for development of CRC in patients with ulcerative colitis. In this issue of Gut , Garrity-Park and colleagues7 ( see page 1226 ) now report that risk for the development of CRC in patients with ulcerative colitis is associated with specific HLA-DR and HLA-DQ alleles encoded at loci within the class II region of the major histocompatibility complex (MHC) on chromosome 6p. The HLA-DR and HLA-DQ molecules are heterodimeric cell surface proteins that present polypeptide antigens derived primarily from extracellular sources to CD4 + T lymphocytes, and play multiple critical roles in adaptive immunity. …
Malignant atrophic papulosis
Authors: R. DEGOS
Journal: British Journal of Dermatology (1979)

The lethal intestino-cutaneous syndrome which we described in 1942 as malignant atrophic papulosis (MAP) has gained various other visceral sites. However, the cutaneous eruption remains the constant and pathognomonic symptom, which, despite its benign appearance harbours a serious prognosis because of the frequently very severe lesions in the small intestine, and sometimes of the nervous system. The very special histological structure shows zones of necrosis (dermal in the skin) due to vasculitis with a tendency to thrombosis, affecting the small vessels below the lesion, and with little or no inflammatory reaction, which differentiates it from other angiitis. The aetiology remains uncertain (?viral) and the treatment is disappointing although heparin appears to have been helpful occasionally.
Role of apoptosis induced by <i>Helicobacter pylori </i>infection in the development of duodenal ulcer
Authors: K Kohda, K Tanaka, Y Aiba, M Yasuda, T Miwa, Y Koga
Journal: Gut (1999)

BACKGROUND Helicobacter pylori affects gastric epithelium integrity by acceleration of apoptosis. However, it remains unclear what product of the bacteria causes apoptosis, or whether or not the apoptosis is involved in the development of ulcers. AIMS To elucidate the factor from H pylori that causes acceleration of apoptosis and the role of apoptosis in the development of duodenal ulcer in H pylori infection. PATIENTS Five H pylori negative healthy volunteers, 47 H pylori positive patients with duodenal ulcer, and 35 H pylori positive patients with gastric ulcer. METHODS An endoscopic examination was carried out to diagnose ulcers and determine their clinical stage. To analyse apoptosis, a cell cycle analysis was performed using biopsy specimens. RESULTS There was a significant correlation between the urease activity of the H pylori strain and the level of apoptosis induced by this bacterial strain. Moreover, in duodenal ulcer patients infected with H pylori , the patients with an active ulcer exhibited a significantly higher level of apoptosis than those with ulcers at both the healing and scarring stages. CONCLUSION These findings suggest that acceleration of apoptosis in the antral mucosa caused by the urease of H pylori plays a crucial role in the development of ulcers in the duodenum.
Improved Clinical Outcome in Recent Years for Men With Metastatic Nonseminomatous Germ Cell Tumors
Authors: Brett S. Carver, Angel M. Serio, Dean Bajorin, Robert J. Motzer, Jason Stasi, George J. Bosl, Andrew J. Vickers, Joel Sheinfeld
Journal: Journal of Clinical Oncology (2007)

The integration of chemotherapy and surgery for metastatic nonseminomatous germ cell tumors (NSGCT) results in survival rates of greater than 80% overall. We evaluated men undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for NSGCT to determine associations between year of treatment and clinical outcome.We evaluated 504 men who underwent PC-RPLND from 1989 to 2002 for NSGCT at our center. Data were obtained from our prospective surgical database and a multivariable logistic regression model was constructed to evaluate variables associated with 15-month relapse in 392 patients with complete data.From 1989 to 1997, clinical stage IIa, IIb, IIc, and III NSGCT was seen in 4%, 20%, 23%, and 47% of patients, respectively, compared with 18%, 26%, 11%, and 38%, respectively, from 1998 to 2002 (P < .001). The median prechemotherapy nodal size for 1989 to 1997 and 1998 to 2002 was 5.0 and 3.5 cm, respectively (P < .001). On multivariable analysis, prechemotherapy retroperitoneal nodal size (odds ratio [OR], 1.12; 95% CI, 1.03 to 1.21; P = .005) and presence of visceral metastasis (OR, 2.10; 95% CI, 1.02 to 4.33; P = .04) were significantly associated with 15-month relapse. Men who received a complete RPLND were significantly less likely to experience relapse (OR, 0.22; 95% CI, 0.09 to 0.50; P < .0005).In more recent years, men are presenting with less advanced metastatic NSGCT. This stage migration together with effective therapy has resulted in an improved relapse-free survival.
Pulmonary rehabilitation in patients with MRC Dyspnoea Scale 2
Authors: W. D.-C. Man, A. Grant, L. Hogg, J. Moore, R. D. Barker, J. Moxham
Journal: Thorax (2010)

but must be openly discussed, communicated and documented.A predicted moderate to high risk of death from community-acquired pneumonia is a highly relevant piece of information required to mount an ethically valid treatment recommendation and decision, particularly in those patients with pneumonia regarded to be a terminal event.Nevertheless, we recalculated the predictions of the CRB-65 score excluding all those who died without having received any ventilator support during hospitalisation.The results are: overall death rate 8618, 2.5%, CRB-65 risk class 1: 0.5%, risk class 2: 1.7% and risk class 3: 12.2%.These numbers support the following conclusions: (1) the CRB-65 score remains useful in predicting deaths in a three class pattern; (2) obviously, virtually no previous study on community-acquired pneumonia truly excluded all patients with treatment limitations.
Evaluating computerised health information systems: hard lessons still to be learnt
Authors: Peter Littlejohns, Jeremy C Wyatt, Linda Garvican
Journal: BMJ (2003)

Enormous investment has gone into computerised hospital information systems worldwide.The estimated costs for each large hospital are about $50m (£33m), yet the overall benefits and costs of hospital information systems have rarely been assessed. 1When systems are evaluated, about three quarters are considered to have failed, 2 and there is no evidence that they improve the productivity of health professionals. 3o generate information that is useful to decision makers, evaluations of hospital information systems need to be multidimensional, covering many aspects beyond technical functionality. 4A major new information and communication technology initiative in South Africa 5 gave us the opportunity to evaluate the introduction of computerisation into a new environment.We describe how the project and its evaluation were set up and examine where the project went wrong.The lessons learnt are applicable to the installation of all hospital information systems. Development of the projectThe project to install a computerised integrated hospital information system in Limpopo (Northern) Province (figure) was the biggest medical informatics project in Africa.The project was initiated in response to a national strategy to restructure health care after the 1994 elections.Changes included shifting resources from tertiary and secondary care to primary care, devolution of management to district level, and redistribution of resources in response to perceived geographical and sectoral need.The success of these initiatives required managerial, administrative, and clinical processes that were efficient, effective, and equitable.Adequate information was considered essential, not only to facilitate the tasks but also for short and long term monitoring.Limpopo Province has 42 hospitals, comprising two mental health institutions, eight regional hospitals (two acting as a tertiary complex with teaching responsibilities), and 32 district hospitals.The area is one of the poorest in South Africa.IBM was awarded the contract for implementation at a cost of 134m Rand (nearly £14m), which represented 2.5% of the province's health and welfare annual budget.
Human CD3 Transgenic Mice: Preclinical Testing of Antibodies Promoting Immune Tolerance
Authors: Chantal Kuhn, Sylvaine You, Fabrice Valette, Geoff Hale, Peter van Endert, Jean-François Bach, Herman Waldmann, Lucienne Chatenoud
Journal: Science Translational Medicine (2011)

Monoclonal antibodies have proven to be potent agents to promote immunological tolerance in animal models of autoimmune disease and transplantation. However, optimal clinical application and pharmaceutical development have been limited by the species specificity of therapeutic antibodies, as well exemplified in the case of anti-CD3 antibodies. Compelling evidence in the nonobese diabetic (NOD) mouse, recently translated to clinical autoimmune insulin-dependent diabetes, demonstrates that a short CD3 antibody treatment effectively and durably controls disease progression. We established transgenic mice expressing the human ε chain of the CD3 complex bred onto the NOD background. These mice developed a high incidence of spontaneous autoimmune diabetes and harbored T cells sensitive both in vitro and in vivo to anti-human CD3 antibodies. Treatment of diabetic transgenic mice with otelixizumab, an anti-human CD3 antibody that has proven effective in the clinic, resulted in durable disease remission dependent on transferable T cell-mediated tolerance. This model should enable the evaluation of anti-human CD3 antibodies to determine their potential clinical utility.
Risk of venous and arterial thrombotic events in patients diagnosed with superficial vein thrombosis: a nationwide cohort study
Authors: Suzanne C. Cannegieter, Erzsébet Horváth-Puhó, Morten Schmidt, Olaf M. Dekkers, Lars Pedersen, Jan P. Vandenbroucke, Henrik T. Sørensen
Journal: Blood (2014)
The Incidence of Microbial Keratitis among Wearers of a 30-Day Silicone Hydrogel Extended-Wear Contact Lens
Authors: Oliver D. Schein, John J. McNally, Joanne Katz, Robin L. Chalmers, James M. Tielsch, Eduardo Alfonso, Mark Bullimore, Denis O’Day, Joseph Shovlin
Journal: Ophthalmology (2005)
Randomized Phase II Study of Multiple Dose Levels of CCI-779, a Novel Mammalian Target of Rapamycin Kinase Inhibitor, in Patients With Advanced Refractory Renal Cell Carcinoma
Authors: Michael B. Atkins, Manuel Hidalgo, Walter M. Stadler, Theodore F. Logan, Janice P. Dutcher, Gary R. Hudes, Young Park, Song-Heng Liou, Bonnie Marshall, Joseph P. Boni, Gary Dukart, Matthew L. Sherman
Journal: Journal of Clinical Oncology (2004)

Purpose To evaluate the efficacy, safety, and pharmacokinetics of multiple doses of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma (RCC). Patients and Methods Patients (n = 111) were randomly assigned to receive 25, 75, or 250 mg CCI-779 weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, survival, and adverse events. Blood samples were collected to determine CCI-779 pharmacokinetics. Results CCI-779 produced an objective response rate of 7% (one complete response and seven partial responses) and minor responses in 26% of these advanced RCC patients. Median time to tumor progression was 5.8 months and median survival was 15.0 months. The most frequently occurring CCI-779–related adverse events of all grades were maculopapular rash (76%), mucositis (70%), asthenia (50%), and nausea (43%). The most frequently occurring grade 3 or 4 adverse events were hyperglycemia (17%), hypophosphatemia (13%), anemia (9%), and hypertriglyceridemia (6%). Neither toxicity nor efficacy was significantly influenced by CCI-779 dose level. Patients were retrospectively classified into good-, intermediate-, or poor-risk groups on the basis of criteria used by Motzer et al for a first-line metastatic RCC population treated with interferon alfa. Within each risk group, the median survivals of patients at each dose level were similar. Conclusion In patients with advanced RCC, CCI-779 showed antitumor activity and encouraging survival and was generally well tolerated over the three dose levels tested.
Monocarboxylate Transporter 1 Deficiency and Ketone Utilization
Authors: Peter M. van Hasselt, Sacha Ferdinandusse, Glen R. Monroe, Jos P.N. Ruiter, Marjolein Turkenburg, Maartje J. Geerlings, Karen Duran, Magdalena Harakalova, Bert van der Zwaag, Ardeshir A. Monavari, Ilyas Okur, Mark J. Sharrard, Maureen Cleary, Nuala O’Connell, Valerie Walker, M. Estela Rubio-Gozalbo, Maaike C. de Vries, Gepke Visser, Roderick H.J. Houwen, Jasper J. van der Smagt, Nanda M. Verhoeven-Duif, Ronald J.A. Wanders, Gijs van Haaften
Journal: New England Journal of Medicine (2014)

Ketoacidosis is a potentially lethal condition caused by the imbalance between hepatic production and extrahepatic utilization of ketone bodies. We performed exome sequencing in a patient with recurrent, severe ketoacidosis and identified a homozygous frameshift mutation in the gene encoding monocarboxylate transporter 1 (SLC16A1, also called MCT1). Genetic analysis in 96 patients suspected of having ketolytic defects yielded seven additional inactivating mutations in MCT1, both homozygous and heterozygous. Mutational status was found to be correlated with ketoacidosis severity, MCT1 protein levels, and transport capacity. Thus, MCT1 deficiency is a novel cause of profound ketoacidosis; the present work suggests that MCT1-mediated ketone-body transport is needed to maintain acid-base balance.
Is Self-Efficacy Associated With Diabetes Self-Management Across Race/Ethnicity and Health Literacy?
Authors: Urmimala Sarkar, Lawrence Fisher, Dean Schillinger
Journal: Diabetes Care (2006)

OBJECTIVE—Although prior research demonstrated that improving diabetes self-efficacy can improve self-management behavior, little is known about the applicability of this research across race/ethnicity and health literacy levels. We examined the relationship between diabetes self-efficacy and self-management behavior in an urban, diverse, low-income population with a high prevalence of limited health literacy. RESEARCH DESIGN AND METHODS—We administered an oral questionnaire in Spanish and English to patients with type 2 diabetes at two primary care clinics at a public hospital. We measured self-efficacy, health literacy, and self-management behaviors using established instruments. We performed multivariate regressions to explore the associations between self-efficacy and self-management, adjusting for clinical and demographic factors. We tested for interactions between self-efficacy, race/ethnicity, and health literacy on self-management. RESULTS—The study participants were ethnically diverse (18% Asian/Pacific Islander, 25% African American, 42% Latino/a, and 15% white), and 52% had limited health literacy (short version of the Test of Functional Health Literacy in Adults score &amp;lt;23). Diabetes self-efficacy was associated with four of the five self-management domains (P &amp;lt; 0.01). After adjustment, with each 10% increase in self-efficacy score, patients were more likely to report optimal diet (0.14 day more per week), exercise (0.09 day more per week), self-monitoring of blood glucose (odds ratio 1.16), and foot care (1.22), but not medication adherence (1.10, P = 0.40). The associations between self-efficacy and self-management were consistent across race/ethnicity and health literacy levels. CONCLUSIONS—Self-efficacy was associated with self-management behaviors in this vulnerable population, across both race/ethnicity and health literacy levels. However, the magnitude of the associations suggests that, among diverse populations, further study of the determinants of and barriers to self-management is warranted. Policy efforts should be focused on expanding the reach of self-management interventions to include ethnically diverse populations across the spectrum of health literacy.
From CME to CPD: getting better at getting better?
Authors: C. du Boulay
Journal: BMJ (2000)

See also p 432 

Continuing medical education is part of the process of lifelong learning that all doctors undertake from medical school until retirement and has traditionally been viewed by the medical profession in terms of updating their knowledge. However, all career grade doctors need skills that extend beyond updating their medical knowledge in order to practise effectively in the modern NHS. Such skills include management, education and training, information technology, audit, communication, and team building. These broader skills are embraced by continuing professional development, which, in a welcome move last year, was endorsed by the Academy of Royal Colleges. Thus the colleges have now accepted responsibility for both continuing medical education and professional development of hospital doctors (with parallel arrangements for general practitioners1). The task is now to establish schemes and develop methods that both achieve the desired outcomes and are seen to do so.

The royal colleges are responsible for providing a framework for continuing professional development; setting educational standards; and monitoring, facilitating, and evaluating activities for their members. Their …