tbuckley/cabot-search huggingface dataset:
Diabetes and the Risk of Lung Cancer
Authors: Gillian C. Hall, C. Michael Roberts, Magdy Boulis, Jingping Mo, Kenneth D. MacRae
Journal: Diabetes Care (2005)

OBJECTIVE—The incidence of some cancers has been reported to be higher in diabetic patients than in the general population. We estimated the incidence of lung cancer in diabetic patients and investigated the hypothesis that the rate of lung cancer is different in diabetic compared with nondiabetic patients. RESEARCH DESIGN AND METHODS—Diabetic patients and age-, sex-, and general practice-matched nondiabetic control subjects were identified from U.K. computerized general practice records (General Practice Research Database), and these records searched for any incident lung cancer, demographic details, and smoking status. Primary lung cancer incidence was calculated and rates compared between diabetic patients and nondiabetic control subjects using multivariate Cox regression, adjusting for age, sex, and smoking. The comparison was repeated for incident diabetic patients followed from diagnosis and after stratifying by diabetic treatment. RESULTS—The incidence of primary lung cancer in all 66,848 diabetic patients was 1.63 per 1,000 patient-years (95% CI 1.48–1.79) and 2.05 per 1,000 patient-years (1.76–2.38) among diabetic patients followed from diagnosis. When compared with nondiabetic control subjects, the hazard ratio was 0.88 (0.79–0.97) for all diabetic patients and 1.12 (0.95–1.34) for those followed from diagnosis. When observation was truncated to allow for shorter life expectancy, the hazard ratio for the total cohort was 0.98 (0.84–1.13), and no association was found with any treatment group. CONCLUSIONS—No increased risk of lung cancer in diabetes was found. We hypothesize that the lower incidence may be partly due to shorter life expectancy.
Prevention is better than cure: time to change the focus of community-acquired pneumonia management
Authors: Tobias Welte
Journal: European Respiratory Journal (2015)

Community-acquired pneumonia is the leading cause of hospital admission for infectious disease in Europe, and a major cause of morbidity and mortality. According to the results of Global Burden of Disease study, in the World Health Organization European region, community-acquired pneumonia accounted for 230 000 (2.3%) deaths and 2.2 million (1.5%) disability-adjusted life-years in 2010, and was ranked the fifth most common cause of death in the continent [1]. The incidence of community-acquired pneumonia increases with age and the burden is therefore set to become greater and more costly with the ageing worldwide population. Increased awareness of the role of adult vaccination is needed to reduce pneumococcal pneumonia rates <http://ow.ly/M3pqj>
THE EFFECT OF A POLYSACCHARIDE-SPLITTING ENZYME ON STREPTOCOCCAL INFECTION
Authors: George K. Hirst
Journal: The Journal of Experimental Medicine (1941)

1. Confirming the observations of other experimenters, it has been found that group A hemolytic streptococci produce a capsule containing a polysaccharide which is similar to, if not identical with, certain high molecular weight sugars found in the mammalian body. 2. Leech extract possesses a powerful enzyme capable of splitting one of the linkages in this polysaccharide and of decapsulating group A and group C hemolytic streptococci in vitro and in vivo. 3. Mice and guinea pigs can be protected from intraperitoneal infection with a virulent group C streptococcus by the intraperitoneal administration of leech extract. In contrast there is little protective action of leech extract in mice infected with group A hemolytic streptococci. 4. The protective effect of leech extract against streptococcal group C infection is probably due to the removal of the capsule in vivo. 5. The capsule of mouse virulent group C streptococci plays a major rôle in the virulence of that microorganism, while the capsule of certain mouse virulent group A streptococci plays little, if any, rôle in virulence, at least when the infection is intraperitoneal in the mouse.
Vascular Targeting Agents as Cancer Therapeutics
Authors: Philip E. Thorpe
Journal: Clinical Cancer Research (2004)

Abstract Vascular targeting agents (VTAs) for the treatment of cancer are designed to cause a rapid and selective shutdown of the blood vessels of tumors. Unlike antiangiogenic drugs that inhibit the formation of new vessels, VTAs occlude the pre-existing blood vessels of tumors to cause tumor cell death from ischemia and extensive hemorrhagic necrosis. Tumor selectivity is conferred by differences in the pathophysiology of tumor versus normal tissue vessels (e.g., increased proliferation and fragility, and up-regulated proteins). VTAs can kill indirectly the tumor cells that are resistant to conventional antiproliferative cancer therapies, i.e., cells in areas distant from blood vessels where drug penetration is poor, and hypoxia can lead to radiation and drug resistance. VTAs are expected to show the greatest therapeutic benefit as part of combined modality regimens. Preclinical studies have shown VTA-induced enhancement of the effects of conventional chemotherapeutic agents, radiation, hyperthermia, radioimmunotherapy, and antiangiogenic agents. There are broadly two types of VTAs, small molecules and ligand-based, which are grouped together, because they both cause acute vascular shutdown in tumors leading to massive necrosis. The small molecules include the microtubulin destabilizing drugs, combretastatin A-4 disodium phosphate, ZD6126, AVE8062, and Oxi 4503, and the flavonoid, DMXAA. Ligand-based VTAs use antibodies, peptides, or growth factors that bind selectively to tumor versus normal vessels to target tumors with agents that occlude blood vessels. The ligand-based VTAs include fusion proteins (e.g., vascular endothelial growth factor linked to the plant toxin gelonin), immunotoxins (e.g., monoclonal antibodies to endoglin conjugated to ricin A), antibodies linked to cytokines, liposomally encapsulated drugs, and gene therapy approaches. Combretastatin A-4 disodium phosphate, ZD6126, AVE8062, and DMXAA are undergoing clinical evaluation. Phase I monotherapy studies have shown that the agents are tolerated with some demonstration of single agent efficacy. Because efficacy is expected when the agents are used with conventional chemotherapeutic drugs or radiation, the results of Phase II combination studies are eagerly awaited.
Long-Term Survival Advantage and Prognostic Factors Associated With Intraperitoneal Chemotherapy Treatment in Advanced Ovarian Cancer: A Gynecologic Oncology Group Study
Authors: Devansu Tewari, James J. Java, Ritu Salani, Deborah K. Armstrong, Maurie Markman, Thomas Herzog, Bradley J. Monk, John K. Chan
Journal: Journal of Clinical Oncology (2015)

Purpose To determine long-term survival and associated prognostic factors after intraperitoneal (IP) chemotherapy in patients with advanced ovarian cancer. Patients and Methods Data from Gynecologic Oncology Group protocols 114 and 172 were retrospectively analyzed. Cox proportional hazards regression models were used for statistical analyses. Results In 876 patients, median follow-up was 10.7 years. Median survival with IP therapy was 61.8 months (95% CI, 55.5 to 69.5), compared with 51.4 months (95% CI, 46.0 to 58.2) for intravenous therapy. IP therapy was associated with a 23% decreased risk of death (adjusted hazard ratio [AHR], 0.77; 95% CI, 0.65 to 0.90; P = .002). IP therapy improved survival of those with gross residual (≤ 1 cm) disease (AHR, 0.75; 95% CI, 0.62 to 0.92; P = .006). Risk of death decreased by 12% for each cycle of IP chemotherapy completed (AHR, 0.88; 95% CI, 0.83 to 0.94; P &lt; .001). Factors associated with poorer survival included: clear/mucinous versus serous histology (AHR, 2.79; 95% CI, 1.83 to 4.24; P &lt; .001), gross residual versus no visible disease (AHR, 1.89; 95% CI, 1.48 to 2.43; P &lt; .001), and fewer versus more cycles of IP chemotherapy (AHR, 0.88; 95% CI, 0.83 to 0.94; P &lt; .001). Younger patients were more likely to complete the IP regimen, with a 5% decrease in probability of completion with each year of age (odds ratio, 0.95; 95% CI, 0.93 to 0.96; P &lt; .001). Conclusion The advantage of IP over intravenous chemotherapy extends beyond 10 years. IP therapy enhanced survival of those with gross residual disease. Survival improved with increasing number of IP cycles.
Diastolic dysfunction in patients with overlap syndrome - An early sign of a high cardiovascular risk?
Authors: Annette Moll, Simone Rack, Albert Moeller, Claudius Teupe
Journal: European Respiratory Journal (2013)

Introduction: COPD and obstructive sleep apnea (OSA) are independent cardiovascular risk factors. Recent data showed an increased cardiovascular mortality in patients with both disorders (overlap syndrome (OS)).

The aim of the study was to determine whether left ventricular diastolic dysfunction (DD) could be detected in patients with OS as a first sign of a high cardiovascular risk.

Methods: We performed a retrospective study in 66 patients with OS and 35 patients with OSA, who underwent a polysomnography and were treated with nasal continuous positive airway pressure in our sleep center from 01/2010 to 04/2012. DD was assessed in the echocardiography by ratio of peak early (E) to peak atrial (A) Doppler mitral valve flow velocity and tissue Doppler evaluation of the early diastolic (e') lengthening velocity.

Results: Apnea-hypopnea-index (/h) (OS: 34,5±22,5 vs OSA: 42,7±22,0), age (years) (61,2±10,0 vs 59,0±6,9) and body mass index (kg/m²) (34,8±6,9 vs 33,9±5,2) showed no differences. Cardiovascular risk factors as arterial hypertension (78,4% vs 62,1%; p=0,177), diabetes mellitus (35,1% vs. 27,6%; p=0,599) and coronary artery disease (21,6% vs. 20,7%; p=1,000) were equally distribute in both groups. We found a significantly increased incidence of diastolic dysfunction (56,2% vs. 20,7%; p=0,008) in patients with OS. This was also observed in both groups with normal pulmonary artery pressure (50,0% vs. 28,5%; p=0,0473).

Conclusions: The early detection of a diastolic dysfunction in patients with OS could alert the clinician to focus on a more intensive therapy. An increased right ventricular afterload seems not to be obligatory for the development of a diastolic dysfunction.
Use of probiotic <i>Lactobacillus</i> preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial
Authors: Mary Hickson, Aloysius L D'Souza, Nirmala Muthu, Thomas R Rogers, Susan Want, Chakravarthi Rajkumar, Christopher J Bulpitt
Journal: BMJ (2007)

To determine the efficacy of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use and that caused by Clostridium difficile.Randomised double blind placebo controlled study.135 hospital patients (mean age 74) taking antibiotics. Exclusions included diarrhoea on admission, bowel pathology that could result in diarrhoea, antibiotic use in the previous four weeks, severe illness, immunosuppression, bowel surgery, artificial heart valves, and history of rheumatic heart disease or infective endocarditis.Consumption of a 100 g (97 ml) drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus twice a day during a course of antibiotics and for one week after the course finished. The placebo group received a longlife sterile milkshake.occurrence of antibiotic associated diarrhoea. Secondary outcome: presence of C difficile toxin and diarrhoea.7/57 (12%) of the probiotic group developed diarrhoea associated with antibiotic use compared with 19/56 (34%) in the placebo group (P=0.007). Logistic regression to control for other factors gave an odds ratio 0.25 (95% confidence interval 0.07 to 0.85) for use of the probiotic, with low albumin and sodium also increasing the risk of diarrhoea. The absolute risk reduction was 21.6% (6.6% to 36.6%), and the number needed to treat was 5 (3 to 15). No one in the probiotic group and 9/53 (17%) in the placebo group had diarrhoea caused by C difficile (P=0.001). The absolute risk reduction was 17% (7% to 27%), and the number needed to treat was 6 (4 to 14).Consumption of a probiotic drink containing L casei, L bulgaricus, and S thermophilus can reduce the incidence of antibiotic associated diarrhoea and C difficile associated diarrhoea. This has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50.National Research Register N0016106821.
The Relationship between GRACE Risk Score and Epicardial Fat Thickness in Patients with Acute Coronary Syndrome
Authors: İlker Gül, Ahmet Çağrı Aykan, Tayyar Gökdeniz, Faruk Boyacı, Ezgi Kalaycıoğlu, Murat Bilgin, Bekir Serhat Yıldız, Mustafa Zungur, Ahmet Taştan, Necdet Batuhan Tamcı, Talat Tavlı, Şükrü Çelik
Journal: Journal of the American College of Cardiology (2013)
Regulation of glutamine metabolism in vitro by bicarbonate ion and pH
Authors: David P. Simpson, Donald J. Sherrard
Journal: Journal of Clinical Investigation (1969)

The effect of variations of medium pH and bicarbonate concentration on glutamine oxidation was studied in slices and mitochondria from dog renal cortex. Decreasing pH and bicarbonate concentration increased the rate of oxidation of glutamine-U-14C to 14CO2 in both slices and mitochondria, an effect comparable to the acute stimulation of glutamine utilization produced by metabolic acidosis. Decreases in the concentration of glutamate and α-ketoglutarate, which accompany metabolic acidosis in the intact animal, also occurred in tissue slices when pH and [HCO3-] were lowered; decrease in α-ketoglutarate but not in glutamate content occurred in mitochondria under these conditions. Study of independent variations of medium pH and [HCO3-] showed that simultaneous changes in both pH and [HCO3-] produced a greater effect on glutamine metabolism than did change in either of these parameters alone.
Vaccination with Ep-CAM Protein or Anti-Idiotypic Antibody Induces Th1-Biased Response against MHC Class I- and II-Restricted Ep-CAM Epitopes in Colorectal Carcinoma Patients
Authors: Szilvia Mosolits, Katja Markovic, Jan-Erik Frödin, Lena Virving, Carl G. M. Magnusson, Michael Steinitz, Jan Fagerberg, Håkan Mellstedt
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The tumor-associated antigen Ep-CAM (epithelial cell adhesion molecule) is overexpressed in colorectal carcinoma (CRC). The aim of the present study was to evaluate and compare the safety and immunogenicity of a recombinant Ep-CAM protein and a human anti-idiotypic antibody (anti-Id) mimicking Ep-CAM. Experimental Design: Patients with resected American Joint Committee on Cancer stages II–IV CRC without remaining macroscopic disease received intradermal/subcutaneous injections of Ep-CAM (400 μg/dose; n = 7) or anti-Id (500 μg/dose; n = 6) at weeks 0, 2, and 6 in combination with granulocyte macrophage colony-stimulating factor (75 μg/day, for 4 consecutive days). Results: Adverse reactions were mild (grade I–II). All patients immunized with the Ep-CAM protein produced Ep-CAM–specific IgG antibodies, predominantly IgG1 and IgG3 subclasses, whereas no humoral response was induced by the anti-Id vaccine. All patients, with one exception in each group, mounted an Ep-CAM–specific proliferative T-cell response. The immune response was more rapid, potent, and protracted after Ep-CAM in comparison with anti-Id vaccination. Interferon-γ-secreting cells (ELISPOT) were detected in both immunization groups against the Ep-CAM protein as well as various Ep-CAM–derived MHC class I- and II-restricted peptides. Flow cytometry analysis showed that Ep-CAM–specific interferon-γ- and perforin-producing cells predominantly resided within CD8+CD56− and CD8dimCD56+ T cells. Conclusions: Ep-CAM protein in combination with granulocyte macrophage colony-stimulating factor induced a long-lasting, Th1-biased humoral and cellular immune response compared with anti-Id. Ep-CAM–specific T cells and natural killer-like T cells responding in a MHC class I- and II-restricted manner were also induced. Vaccination with Ep-CAM protein may warrant further investigation as a novel therapeutic approach to CRC.
Theory of mind in schizophrenia: Damaged module or deficit in cognitive coordination?
Authors: David Leiser, Udi Bonshtein
Journal: Behavioral and Brain Sciences (2003)

Abstract Schizophrenics exhibit a deficit in theory of mind (ToM), but an intact theory of biology (ToB). One explanation is that ToM relies on an independent module that is selectively damaged. Phillips &amp; Silverstein's analyses suggest an alternative: ToM requires the type of coordination that is impaired in schizophrenia, whereas ToB is spared because this type of coordination is not involved.
Phase II study of everolimus in children and adults with neurofibromatosis type 2 and progressive vestibular schwannomas
Authors: Matthias A. Karajannis, Geneviève Legault, Mari Hagiwara, Filippo G. Giancotti, Alexander Filatov, Anna Derman, Tsivia Hochman, Judith D. Goldberg, Emilio Vega, Jeffrey H. Wisoff, John G. Golfinos, Amanda Merkelson, J. Thomas Roland, Jeffrey C. Allen
Journal: Neuro-Oncology (2013)

Activation of the mammalian target of rapamycin (mTOR) signaling pathway is thought to be a key driver of tumor growth in Merlin (NF2)-deficient tumors. Everolimus is an oral inhibitor of mTOR complex 1 (mTORC1) with antitumor activity in a variety of cancers.We conducted a single-institution, prospective, 2-stage, open-label phase II study to estimate the response rate to everolimus in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannoma (VS). Ten eligible patients were enrolled, including 2 pediatric patients. Everolimus was administered at a daily dose of 10 mg (adults) or 5 mg/m(2)/day (children <18 y) orally in continuous 28-day courses, for up to 12 courses. Response was assessed every 3 months with MRI, using 3-dimensional volumetric tumor analysis, and audiograms. Nine patients were evaluable for the primary response, defined as ≥15% decrease in VS volume. Hearing response was evaluable as a secondary endpoint in 8 patients.None of the 9 patients with evaluable disease experienced a clinical or MRI response. No objective imaging or hearing responses were observed in stage 1 of the trial, and the study was closed according to predefined stopping rules.Everolimus is ineffective for the treatment of progressive VS in NF2 patients. We are currently conducting a pharmacokinetic/pharmacodynamic ("phase 0") study of everolimus in presurgical VS patients to elucidate the biological basis for apparent treatment resistance to mTORC1 inhibition in these tumors.
Application of in-situ hybridization techniques to study human preimplantation embryos: a review
Authors: E Coonen
Journal: Human Reproduction Update (1998)

Although the first in-situ hybridization (ISH) experiments were performed more than two decades ago, it was not until 1987 that the technique was implemented in the study of preimplantation. Since then, several groups have explored the feasibility of using the ISH technique as a diagnostic tool to study the genomic constitution of human preimplantation embryos. Though a fair number of such ISH studies have been published and unravelling of the embryos' genomic secrets proceeds with great strides, there are still many challenges in this area of research. The scope of this review is to outline the research and diagnostic applications of single and multicolour (fluorescence) ISH to study the chromosomal content of human preimplantation embryos and to discuss the implications for human preimplantation genetic diagnosis. Current hybridization techniques are being discussed, including the capabilities and pitfalls of this approach when applied to human preimplantation embryos. Finally, future perspectives for the ISH technique in studying the genomic constitution of preimplantation embryos are reviewed.
A biomechanical perspective: do foot orthoses work?
Authors: B Heiderscheit, J Hamill, D Tiberio
Journal: British Journal of Sports Medicine (2001)

Foot orthoses have become an integral part of the treatment of injuries of the foot, ankle, and lower extremity. From a biomechanical perspective, they offer a means of resolving symptoms by placing the foot and the lower extremity in a more advantageous position thus altering applied tissue stresses. Ample evidence exists, based on subjective pain relief and symptom resolution, to support the continued use of these devices. However, scientific evidence to confirm these observations is equivocal.

If there is a biomechanical basis for patient improvement, one of many possible kinematic or kinetic parameters should be altered by foot orthoses. Increased magnitude of the pronation angle and increased pronation velocity have been postulated as risk factors for lower extremity injury. A number of investigations have shown the potential of an orthosis with an external medial post to decrease the magnitude of pronation.1 Not unexpectedly, a decrease in tibial internal rotation has also been shown with medially posted orthoses.2 However, Johanson et al 1 observed that a non-posted orthotic shell reduced the maximum pronation angle as much as either a forefoot or a rearfoot post, as well as a combination of a forefoot and …
Evolving Paradigms in the Treatment of Newly Diagnosed Multiple Myeloma
Authors: Alessandra Larocca, Antonio Palumbo
Journal: Journal of the National Comprehensive Cancer Network (2011)

The treatment of multiple myeloma has undergone significant changes in the past few years. The introduction of novel agents, such as the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, has dramatically improved the outcome of this disease and considerably increased the treatment options available. Several trials have shown the advantages linked to the use of novel agents both in young patients, who are considered eligible for transplantation, and elderly patients, for whom a conventional therapy should be considered. These novel agents may increase the efficacy of autologous stem cell transplantation with deeper and long-lasting response. In the transplant setting, different novel agent combinations have proved to be superior to the traditional vincristine-doxorubicin-dexamethasone. Similarly, novel agents have also changed the treatment paradigm of patients not eligible for transplantation, thus replacing the traditional melphalan-prednisone approach. Preliminary data also support the role of consolidation and maintenance therapy to further improve outcomes. This article provides an overview of the latest strategies, including novel agents used to treat patients with multiple myeloma, both in the transplant and nontransplant settings.