tbuckley/cabot-search huggingface dataset:
State Payer Mandates to Cover Care in US Oncology Trials: Do Science and Ethics Matter?
Authors: P. L. Taylor
Journal: JNCI Journal of the National Cancer Institute (2010)

In the United States, Medicare-eligible participants’ costs for routine care and complications from cancer clinical trials are covered by Medicare, but other people depend on state insurance mandates to assure coverage. State mandates were reviewed for requirements to assure trials’ scientific and ethical soundness, whom they covered and omitted, scope, and coverage for participants’ research-related injuries in addition to routine care costs. Twenty-six states mandated coverage. Four states (15%) required scientific peer review for all studies. For 20 states (80%), an approved investigational new drug qualified as scientific review. In 10 states (38%), institutional review board (IRB) approval could replace scientific review. Twenty-four states (92%) permitted trials without academic medical connection. All states covered privately insured patients; seven (27%) included government and Medicaid patients. Fourteen states (54%) covered phase I to phase IV trials. Sixteen states (62%) covered treatment trials only; one (4%) covered prevention, detection, treatment, and palliation. Thirteen states (50%) covered research-related injuries. Only seven states (27%) required IRB approval. Three states (12%) required commensurate risks and benefits; 23 (88%) had no standard. Eight states (31%) required clinical equipoise with standard care; eight (31%) had no standard; and remaining states (46%) had unique standards. Two states (8%) addressed publication or registries. Most states did not demand independent scientific review, IRB review, or basic ethical features of high-quality trials; provided partial coverage; omitted prevention, detection, and palliation research; and omitted mandated coverage for research-related injuries. Few required evaluation, independence in publication, or posting trial results. Further research on the impact of diverse state choices would improve policy making.
A prospective randomized trial of fluorouracil versus fluorouracil plus cisplatin in the treatment of metastatic colorectal cancer: a Hoosier Oncology Group trial.
Authors: P J Loehrer, S Turner, P Kubilis, S Hui, J Correa, R Ansari, D Stephens, R Woodburn, S Meyer
Journal: Journal of Clinical Oncology (1988)

From May 1984 through December 1986, 141 patients with metastatic adenocarcinoma of the colon or rectum were entered on this Hoosier Oncology Group (HOG) trial evaluating the role of cisplatin in systemic therapy. Patients were stratified by the presence or absence of hepatic metastases and by performance status, and were subsequently randomized to receive fluorouracil (5-FU) (15 mg/kg/wk) alone or the same dose of 5-FU plus cisplatin (60 mg/m2 every 3 weeks). The total duration of treatment was six cycles (18 weeks). In 132 fully evaluable patients the objective response rates were 19% for 5-FU and 22% for 5-FU plus cisplatin. Statistically, the median survival times of 40 and 39 weeks were not significantly different (P = .62). However, the median duration of remission (MDR) was superior (P = .05) for 5-FU alone. This study fails to confirm clinically significant synergy of 5-FU plus cisplatin in the treatment of metastatic colorectal cancer.
Cutaneous sarcoidosis successfully treated with topical tacrolimus
Authors: N. Katoh, H. Mihara, H. Yasuno
Journal: British Journal of Dermatology (2002)

Sarcoidosis is a disorder characterized by macrophage- and T-cell-mediated responses to as yet unidentified infectious antigens or autoantigens. We describe a 62-year-old woman with a 10-year history of orange–yellow plaques of sarcoidosis on her face. Her cutaneous lesions responded to topical tacrolimus ointment after unsuccessful treatment with topical and systemic corticosteroids. No adverse effects were noted with topical tacrolimus in this patient. We discuss the mode of action by which this immunosuppressive agent may act against sarcoidosis.
Lung Dendritic Cells in Respiratory Viral Infection and Asthma: From Protection to Immunopathology
Authors: Bart N. Lambrecht, Hamida Hammad
Journal: Annual Review of Immunology (2012)

Lung dendritic cells (DCs) bridge innate and adaptive immunity, and depending on context, they also induce a Th1, Th2, or Th17 response to optimally clear infectious threats. Conversely, lung DCs can also mount maladaptive Th2 immune responses to harmless allergens and, in this way, contribute to immunopathology. It is now clear that the various aspects of DC biology can be understood only if we take into account the functional specializations of different DC subsets that are present in the lung in homeostasis or are attracted to the lung as part of the inflammatory response to inhaled noxious stimuli. Lung DCs are heavily influenced by the nearby epithelial cells, and a model is emerging whereby direct communication between DCs and epithelial cells determines the outcome of the pulmonary immune response. Here, we have approached DC biology from the perspective of viral infection and allergy to illustrate these emerging concepts.
Sister Chromatid Exchange and Cell Cycle Progression in Cultured Lymphocytes From Patients With Chronic Lymphatic Leukemia&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M A McDonald, P H Fitzgerald
Journal: JNCI Journal of the National Cancer Institute (1979)

Sister chromatid exchange (SCE) was significantly increased in patients who had chronic lymphatic leukemia (CLL) and who had received therapy compared with untreated patients and normal controls. Elevated SCE appeared to be a function of the therapy and not the leukemia. Differential chromatid staining was used to identify successive cell reproduction cycles. In comparison to normal lymphocytes, the cells responding to phytohemagglutinin in CLL cultures showed no evidence of retarded progression through successive cell cycles.
Skeletal muscle microbiopsy: a validation study of a minimally invasive technique
Authors: M. Hayot, A. Michaud, C. Koechlin, M-A. Caron, P. LeBlanc, C. Préfaut, F. Maltais
Journal: European Respiratory Journal (2005)

The study of the peripheral skeletal muscle function in patients with chronic obstructive pulmonary disease (COPD) is of growing interest, but often requires biopsies, usually with the Bergström technique. The current study was designed to test the validity of a minimally invasive technique: the microbiopsy. In 17 patients with COPD and four normal subjects, two specimens of the vastus lateralis were taken percutaneously under local anaesthesia, one with a 16-gauge needle (microbiopsy) and the other with the Bergström needle. The enzymatic activity of citrate synthase (CS) and phosphofructokinase (PFK), and the myosin heavy chain (MyoHC) composition were measured for both techniques. The subjects reported no pain or much less with the microbiopsy compared with the Bergström biopsy. The microbiopsy sample weight reached 55±17 mg. The two techniques showed excellent agreement for CS activity and MyoHC composition. The PFK activity did not differ statistically between the techniques, but the agreement was moderate. The agreement between both biopsy techniques was stable over time. The median (range) fibre number within the microbiopsy specimens was 144 (38–286). In conclusion, the current study shows the feasibility and validity of a minimally invasive muscle biopsy technique that appears more comfortable for subjects, compared with the Bergström technique.
Clinical Outcomes and Cost-effectiveness of Continuous Positive Airway Pressure to Manage Obstructive Sleep Apnea in Patients With Type 2 Diabetes in the U.K.
Authors: Julian F. Guest, Monica Panca, Erikas Sladkevicius, Shahrad Taheri, John Stradling
Journal: Diabetes Care (2014)

To assess clinical outcomes and cost-effectiveness of using continuous positive airway pressure (CPAP) to manage obstructive sleep apnea (OSA) in patients with type 2 diabetes (T2D) from the perspective of the U.K.'s National Health Service (NHS).Using a case-control design, 150 CPAP-treated patients with OSA and T2D were randomly selected from The Health Improvement Network (THIN) database (a nationally representative database of patients registered with general practitioners in the U.K.) and matched with 150 OSA and T2D patients from the same database who were not treated with CPAP. The total NHS cost and outcomes of patient management in both groups over 5 years and the cost-effectiveness of CPAP compared with no CPAP treatment were estimated.Using CPAP was associated with significantly lower blood pressure at 5 years and increasingly lower HbA1c levels over 5 consecutive years compared with untreated OSA patients. At 5 years, the HbA1c level in the CPAP-treated group was 8.2% (66.0 mmol/mol) vs. 12.1% (108.4 mmol/mol) in the control group (P < 0.03). Use of CPAP significantly increased patients' health status by 0.27 quality-adjusted life years (QALYs) per patient over 5 years (P < 0.001) and NHS management costs by £4,141 per patient over 5 years; the cost per QALY gained with CPAP was £15,337.Initiating treatment with CPAP in OSA patients with T2D leads to significantly lower blood pressure and better controlled diabetes and affords a cost-effective use of NHS resources. These observations have the potential for treatment modification if confirmed in a prospective study.
Back pain in childhood.
Authors: P N Tyrrell, V N Cassar-Pullicino, S M Eisenstein, J F Monach, A J Darby, I W McCall
Journal: Annals of the Rheumatic Diseases (1996)

Case history A 9 year old girl was referred with a three month history of low back pain which was related to increased physical activity, radiating to both legs.Periodic weakness in both legs was associated with occasional paraesthesiae in both feet.There were no bladder, bowel, or other systemic symptoms.Before the onset of back pain the child had been well, with no his- tory of any trauma.On examination, she appeared to be of short stature for age, but of normal proportion.On standing there was a hyperlordosis of the thoracolumbar spine.Percussion over the lum- bar spine at the L2/L3 level elicited marked tenderness.There was a generalised reduction of all spinal movements.Straight leg raising was 40 degrees bilaterally, with limitation due to low back pain.Neurological examination of the lower limbs was normal.She was afebrile and general systemic examination was normal.Following initial radiographic examination, she
Associations between Active Travel to Work and Overweight, Hypertension, and Diabetes in India: A Cross-Sectional Study
Authors: Christopher Millett, Sutapa Agrawal, Ruth Sullivan, Mario Vaz, Anura Kurpad, A. V. Bharathi, Dorairaj Prabhakaran, Kolli Srinath Reddy, Sanjay Kinra, George Davey Smith, Shah Ebrahim
Journal: PLoS Medicine (2013)

Increasing active travel (walking, bicycling, and public transport) is promoted as a key strategy to increase physical activity and reduce the growing burden of noncommunicable diseases (NCDs) globally. Little is known about patterns of active travel or associated cardiovascular health benefits in low- and middle-income countries. This study examines mode and duration of travel to work in rural and urban India and associations between active travel and overweight, hypertension, and diabetes.Cross-sectional study of 3,902 participants (1,366 rural, 2,536 urban) in the Indian Migration Study. Associations between mode and duration of active travel and cardiovascular risk factors were assessed using random-effect logistic regression models adjusting for age, sex, caste, standard of living, occupation, factory location, leisure time physical activity, daily fat intake, smoking status, and alcohol use. Rural dwellers were significantly more likely to bicycle (68.3% versus 15.9%; p<0.001) to work than urban dwellers. The prevalence of overweight or obesity was 50.0%, 37.6%, 24.2%, 24.9%; hypertension was 17.7%, 11.8%, 6.5%, 9.8%; and diabetes was 10.8%, 7.4%, 3.8%, 7.3% in participants who travelled to work by private transport, public transport, bicycling, and walking, respectively. In the adjusted analysis, those walking (adjusted risk ratio [ARR] 0.72; 95% CI 0.58-0.88) or bicycling to work (ARR 0.66; 95% CI 0.55-0.77) were significantly less likely to be overweight or obese than those travelling by private transport. Those bicycling to work were significantly less likely to have hypertension (ARR 0.51; 95% CI 0.36-0.71) or diabetes (ARR 0.65; 95% CI 0.44-0.95). There was evidence of a dose-response relationship between duration of bicycling to work and being overweight, having hypertension or diabetes. The main limitation of the study is the cross-sectional design, which limits causal inference for the associations found.Walking and bicycling to work was associated with reduced cardiovascular risk in the Indian population. Efforts to increase active travel in urban areas and halt declines in rural areas should be integral to strategies to maintain healthy weight and prevent NCDs in India. Please see later in the article for the Editors' Summary.
A letter to the next secretary of state for health
Authors: G. Iacobucci, R. Coombes, F. Godlee
Journal: BMJ (2015)

<h3>Abstract</h3> Siamese fighting fish, commonly known as betta, are among the world’s most popular and morphologically diverse pet fish, but the genetic processes leading to their domestication and phenotypic diversification are largely unknown. We assembled de novo the genome of a wild <i>Betta splendens</i> and whole-genome sequenced multiple individuals across five species within the <i>B. splendens</i> species complex, including wild populations and domesticated ornamental betta. Given our estimate of the mutation rate from pedigrees, our analyses suggest that betta were domesticated at least 1,000 years ago, centuries earlier than previously thought. Ornamental betta individuals have variable contributions from other <i>Betta</i> species and have also introgressed into wild populations of those species. We identify <i>dmrt1</i> as the main sex determination gene in ornamental betta but not in wild <i>B. splendens</i>, and find evidence for recent directional selection at the X-allele of the locus. Furthermore, we find genes with signatures of recent, strong selection that have large effects on color in specific parts of the body, or the shape of individual fins, and are almost all unlinked. Our results demonstrate how simple genetic architectures paired with anatomical modularity can lead to vast phenotypic diversity generated during animal domestication, and set the stage for using betta as a modern system for evolutionary genetics. <h3>One-Sentence Summary</h3> Genomic analyses reveal betta fish were domesticated more than 1,000 years ago and the genes that changed in the process.
Prostate Cancer Radiosensitization through Poly(ADP-Ribose) Polymerase-1 Hyperactivation
Authors: Ying Dong, Erik A. Bey, Long-Shan Li, Wareef Kabbani, Jingsheng Yan, Xian-Jin Xie, Jer-Tsong Hsieh, Jinming Gao, David A. Boothman
Journal: Cancer Research (2010)

Abstract The clinical experimental agent, β-lapachone (β-lap; Arq 501), can act as a potent radiosensitizer in vitro through an unknown mechanism. In this study, we analyzed the mechanism to determine whether β-lap may warrant clinical evaluation as a radiosensitizer. β-Lap killed prostate cancer cells by NAD(P)H:quinone oxidoreductase 1 (NQO1) metabolic bioactivation, triggering a massive induction of reactive oxygen species, irreversible DNA single-strand breaks (SSB), poly(ADP-ribose) polymerase-1 (PARP-1) hyperactivation, NAD+/ATP depletion, and μ-calpain–induced programmed necrosis. In combination with ionizing radiation (IR), β-lap radiosensitized NQO1+ prostate cancer cells under conditions where nontoxic doses of either agent alone achieved threshold levels of SSBs required for hyperactivation of PARP-1. Combination therapy significantly elevated SSB level, γ-H2AX foci formation, and poly(ADP-ribosylation) of PARP-1, which were associated with ATP loss and induction of μ-calpain–induced programmed cell death. Radiosensitization by β-lap was blocked by the NQO1 inhibitor dicoumarol or the PARP-1 inhibitor DPQ. In a mouse xenograft model of prostate cancer, β-lap synergized with IR to promote antitumor efficacy. NQO1 levels were elevated in ∼60% of human prostate tumors evaluated relative to adjacent normal tissue, where β-lap might be efficacious alone or in combination with radiation. Our findings offer a rationale for the clinical utilization of β-lap (Arq 501) as a radiosensitizer in prostate cancers that overexpress NQO1, offering a potentially synergistic targeting strategy to exploit PARP-1 hyperactivation. Cancer Res; 70(20); 8088–96. ©2010 AACR.
Proliferation and differentiation of fetal rat pulmonary epithelium in the absence of mesenchyme.
Authors: R R Deterding, J M Shannon
Journal: Journal of Clinical Investigation (1995)

Previous studies have shown that pulmonary mesenchyme is required to maintain epithelial viability and to support branching morphogenesis and cytodifferentiation. We have examined whether pulmonary mesenchyme can be replaced by a medium containing a combination of soluble factors. Day 13-14 fetal rat distal lung epithelium was enzymatically separated from its mesenchyme, enrobed in EHS tumor matrix, and cultured for 5 d in medium containing concentrated bronchoalveolar lavage, EGF, acidic fibroblast growth factor, cholera toxin, insulin, and FBS (TGM), or in control medium containing only FBS. After 5 d in culture, marked growth and morphological changes occurred in epithelial rudiments cultured in TGM, whereas no changes were seen in controls. [3H]Thymidine incorporation and nuclear labeling indices during the last 24 h of culture confirmed that epithelial rudiments cultured in TGM had significant proliferative capacities. Evaluation of surfactant protein gene expression by Northern analysis, in situ hybridization, and immunocytochemistry demonstrated that distal lung epithelial differentiation progressed in TGM. Ultrastructural analysis demonstrated that fetal distal lung epithelium cultured in TGM contained lamellar bodies and deposited a basal lamina. These results are the first demonstration that sustained proliferation and differentiation of glandular stage distal pulmonary epithelium can proceed in the absence of mesenchyme.
Deficient natural killer cell cytotoxicity in patients with IKK-γ/NEMO mutations
Authors: Jordan S. Orange, Scott R. Brodeur, Ashish Jain, Francisco A. Bonilla, Lynda C. Schneider, Roberto Kretschmer, Samuel Nurko, Wendy L. Rasmussen, Julia R. Köhler, Stephen E. Gellis, Betsy M. Ferguson, Jack L. Strominger, Jonathan Zonana, Narayanaswamy Ramesh, Zuhair K. Ballas, Raif S. Geha
Journal: Journal of Clinical Investigation (2002)

NF-κB essential modifier (NEMO), also known as IKK-γ, is a member of the I-κB kinase complex responsible for phosphorylating I-κB, allowing the release and activation of NF-κB. Boys with an expressed NEMO mutation have an X-linked syndrome characterized by hypohidrotic ectodermal dysplasia with immune deficiency (HED-ID). The immunophenotype resulting from NEMO mutation is highly variable, with deficits in both T and B cell responses. We evaluated three patients with NEMO mutations (L153R, Q403X, and C417R) and HED-ID who had evidence of defective CD40 signaling. All three patients had normal percentages of peripheral blood NK cells, but impaired NK cell cytotoxic activity. This was not due to a generalized defect in cytotoxicity because antibody-dependent cellular cytotoxicity was intact. This abnormality was partially reversed by in vitro addition of IL-2, which was also able to induce NF-κB activation. In one patient with recurrent cytomegalovirus infections, administration of IL-2 partially corrected the NK cell killing deficit. These data suggest that NEMO participates in signaling pathways leading to NK cell cytotoxicity and that IL-2 can activate NF-κB and partially overcome the NK cell defect in patients with NEMO mutations.
Human recombinant interleukin 1 stimulates collagenase and prostaglandin E2 production by human synovial cells.
Authors: J M Dayer, B de Rochemonteix, B Burrus, S Demczuk, C A Dinarello
Journal: Journal of Clinical Investigation (1986)

The pathogenesis and progression of rheumatoid arthritis involves the production of biologically active lymphokines and monokines. Of these, interleukin 1 (IL-1) has been somewhat of a controversial molecule because it seems to evoke various biological responses in several different tissues. In these studies we demonstrate that three biological properties of human monocyte-derived IL-1 (T-lymphocyte activation and human synovial cell prostaglandin E2 and collagenase production) co-purify. The complementary DNA for the prominent pI 7 form of human IL-1 was expressed, purified, and tested. Any controversy now appears resolved since homogeneous recombinant human IL-1 stimulates prostaglandin E2 and collagenase from human synovial cells as well as activates T cells in vitro.
Clinical relevance of resistant strains of Helicobacter pylori: a review of current data
Authors: F Megraud, H P Doermann
Journal: Gut (1998)

Acquired resistance of Helicobacter pylori to metronidazole and clarithromycin has been reported, with metronidazole resistance being very common. This has an important clinical impact on dual therapies, as well as on the standard triple therapies. However, when antisecretory drug based triple therapies with amoxycillin or clarithromycin and metronidazole are used, the resistance can be overcome in up to 75% of the cases in most of the studies. Clarithromycin seems to be a better choice than amoxycillin to achieve this goal. Nevertheless, resistance to metronidazole remains a risk factor for treatment failure. The most precise information comes from studies in which minimum inhibitory concentrations (MICs) are reported as well as whether the strain is susceptible or resistant. Few data are available from clinical trials to measure the impact of clarithromycin resistance. However, such resistance seems to have a negative impact on the clinical outcome of treatment. It is of greater importance that H pylori resistance is closely monitored in the future.