tbuckley/cabot-search huggingface dataset:
Hemodynamic Effects of Volume Expansion in Patients With Cardiac Tamponade
Authors: Jaume Sagristà-Sauleda, Juan Angel, Antonia Sambola, G. Permanyer-Miralda
Journal: Circulation (2008)

Background— Volume expansion has been proposed as an alternative treatment for cardiac tamponade; however, the scientific evidence for this recommendation is very poor. Methods and Results— Forty-nine unselected patients (23 males; age 55±16 years) with large pericardial effusion and hemodynamic tamponade underwent fluid overload with intravenous administration of 500 mL of normal saline over 10 minutes. Cardiac index and intrapericardial, left ventricular end-diastolic, right atrial, and right ventricular end-diastolic pressures were measured during basal state (tamponade), after fluid overload, and after pericardiocentesis. Twenty-eight patients (57%) had physical signs of tamponade, and 10 (20%) were hypotensive. Size of pericardial effusion was 31±13 mm. Initial mean arterial pressure was 88±21 mm Hg, and cardiac index was 2.46±0.80 L · min −1 · m −2 . Intrapericardial pressure was 8.31±5.98 mm Hg. Volume expansion caused a significant increase in mean arterial pressure (from 88±21 to 94±23 mm Hg, P =0.003) and cardiac index (from 2.46±0.80 to 2.64±0.68 L · min −1 · m −2 , P =0.013), as well as in intrapericardial pressure (from 8.31±5.98 to 11.02±6.27 mm Hg, P =0.0001), right atrial pressure (from 9.76±5.91 to 12.82±6.34 mm Hg, P =0.0001), and left ventricular end-diastolic pressure (from 14.21±5.97 to 19.48±6.19 mm Hg, P =0.0001). Cardiac index increased by &gt;10% in 23 patients (47%), remained unchanged in 11 (22%), and decreased in 15 (31%). No patient developed clinical complications. Predictors of this favorable response were systolic blood pressure &lt;100 mm Hg and low cardiac index. Conclusions— Approximately one half of patients with cardiac tamponade develop a significant increase in cardiac output after volume overload. Low systolic blood pressure (&lt;100 mm Hg) at baseline was the simplest clinical finding that was predictive of this favorable response.
Early Discontinuation and Nonadherence to Adjuvant Hormonal Therapy in a Cohort of 8,769 Early-Stage Breast Cancer Patients
Authors: Dawn L. Hershman, Lawrence H. Kushi, Theresa Shao, Donna Buono, Aaron Kershenbaum, Wei-Yann Tsai, Louis Fehrenbacher, Scarlett Lin Gomez, Sunita Miles, Alfred I. Neugut
Journal: Journal of Clinical Oncology (2010)

Purpose While studies have found that adjuvant hormonal therapy for hormone-sensitive breast cancer (BC) dramatically reduces recurrence and mortality, adherence to medications is suboptimal. We investigated the rates and predictors of early discontinuation and nonadherence to hormonal therapy in patients enrolled in Kaiser Permanente of Northern California health system. Patients and Methods We identified women diagnosed with hormone-sensitive stage I-III BC from 1996 to 2007 and used automated pharmacy records to identify hormonal therapy prescriptions and dates of refill. We used Cox proportional hazards regression models to analyze factors associated with early discontinuation and nonadherence (medication possession ratio &lt; 80%) of hormonal therapy. Results We identified 8,769 patients with BC who met our eligibility criteria and who filled at least one prescription for tamoxifen (43%), aromatase inhibitors (26%), or both (30%) within 1 year of diagnosis. Younger or older age, lumpectomy (v mastectomy), and comorbidities were associated with earlier discontinuation, while Asian race, being married, earlier year at diagnosis, receipt of chemotherapy or radiotherapy, and longer prescription refill interval were associated with completion of 4.5 years of therapy. Of those who continued therapy, similar factors were associated with full adherence. Women age younger than 40 years had the highest risk of discontinuation (hazard ratio, 1.51; 95% CI, 1.23 to 1.85). By 4.5 years, 32% discontinued therapy, and of those who continued, 72% were fully adherent. Conclusion Only 49% of patients with BC took adjuvant hormonal therapy for the full duration at the optimal schedule. Younger women are at high risk of nonadherence. Interventions to improve adherence and continuation of hormonal therapy are needed, especially for younger women.
Gene Regulatory Networks in Cardiac Conduction System Development
Authors: Nikhil V. Munshi
Journal: Circulation Research (2012)

The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Given its critical role in coordinating cardiac performance, a detailed analysis of the molecular mechanisms underlying conduction system formation should inform our understanding of arrhythmia pathophysiology and affect the development of novel therapeutic strategies. Historically, the ability to distinguish cells of the conduction system from neighboring working myocytes presented a major technical challenge for performing comprehensive mechanistic studies. Early lineage tracing experiments suggested that conduction cells derive from cardiomyocyte precursors, and these claims have been substantiated by using more contemporary approaches. However, regional specialization of conduction cells adds an additional layer of complexity to this system, and it appears that different components of the conduction system utilize unique modes of developmental formation. The identification of numerous transcription factors and their downstream target genes involved in regional differentiation of the conduction system has provided insight into how lineage commitment is achieved. Furthermore, by adopting cutting-edge genetic techniques in combination with sophisticated phenotyping capabilities, investigators have made substantial progress in delineating the regulatory networks that orchestrate conduction system formation and their role in cardiac rhythm and physiology. This review describes the connectivity of these gene regulatory networks in cardiac conduction system development and discusses how they provide a foundation for understanding normal and pathological human cardiac rhythms.
Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough
Authors: Julie Marchant, Ian Brent Masters, Anita Champion, Helen Petsky, Anne B Chang
Journal: Thorax (2012)

<h3>Background</h3> Despite guideline recommendations, there are no published randomised controlled trial data on the efficacy of antibiotics for chronic wet cough in children. The majority of children with chronic wet cough have protracted bacterial bronchitis (PBB), a recognised condition in multiple national guidelines. The authors conducted a parallel 1:1 placebo randomised controlled trial to test the hypothesis that a 2-week course of amoxycillin clavulanate is efficacious in the treatment of children with chronic wet cough. <h3>Methods</h3> 50 children (median age 1.9 years, IQR 0.9–5.1) with chronic (&gt;3 weeks) wet cough were randomised to 2 weeks of twice daily oral amoxycillin clavulanate (22.5 mg/kg/dose) or placebo. The primary outcome was 'cough resolution' defined as a &gt;75% reduction in the validated verbal category descriptive cough score within 14 days of treatment compared with baseline scores, or cessation of cough for &gt;3 days. In selected children, flexible bronchoscopy and bronchoalveolar lavage (BAL) were undertaken at baseline. <h3>Results</h3> Cough resolution rates (48%) were significantly higher in children who received amoxycillin clavulanate compared with those who received placebo (16%), p=0.016. The observed difference between proportions was 0.32 (95% CI 0.08 to 0.56). Post treatment, median verbal category descriptive score in the amoxycillin clavulanate group of 0.5 (IQR 0.0–2.0) was significantly lower than in the placebo group, 2.25 (IQR 1.15–2.9) (p=0.02). Pre-treatment BAL data were consistent with PBB in the majority of children, with no significant difference between groups. <h3>Conclusion</h3> A 2-week course of amoxycillin clavulanate will achieve cough resolution in a significant number of children with chronic wet cough. BAL data support the diagnosis of PBB in the majority of these children. <h3>Clinical trial number</h3> ACTRN 12605000533695.
Alterations in rRNA–mRNA Interaction during Plastid Evolution
Authors: Kyungtaek Lim, Ichizo Kobayashi, Kenta Nakai
Journal: Molecular Biology and Evolution (2014)

Translation initiation depends on the recognition of mRNA by a ribosome. For this to occur, prokaryotes primarily use the Shine-Dalgarno (SD) interaction, where the 3'-tail of small subunit rRNA (core motif: 3'CCUCC) forms base pairs with a complementary signal sequence in the 5'-untranslated region of mRNA. Here, we examined what happened to SD interactions during the evolution of a cyanobacterial endosymbiont into modern plastids (including chloroplasts). Our analysis of available complete plastid genome sequences revealed that the majority of plastids retained SD interactions but with varying levels of usage. Parallel losses of SD interactions took place in plastids of Chlorophyta, Euglenophyta, and Chromerida/Apicomplexa lineages, presumably related to their extensive reductive evolution. Interestingly, we discovered that the classical SD interaction (3'CCUCC/5'GGAGG [rRNA/mRNA]) was replaced by an altered SD interaction (3'CCCU/5'GGGA or 3'CUUCC/5'GAAGG) through coordinated changes in the sequences of the core rRNA motif and its paired mRNA signal. These changes in plastids of Chlorophyta and Euglenophyta proceeded through intermediate stages that allowed both the classical and altered SD interactions. This coevolution between the rRNA motif and the mRNA signal demonstrates unexpected plasticity in the translation initiation machinery.
Twins and maternal smoking: ordeals for the fetal origins hypothesis? A cohort study
Authors: S. Williams, R. Poulton
Journal: BMJ (1999)

# Twins and maternal smoking: ordeals for the fetal origins hypothesis? A cohort study {#article-title-2} Objective: To assess the direct and indirect effects of being a twin, maternal smoking, birth weight, and mother's height on blood pressure at ages 9 and 18 years. Design: Longitudinal study. Subjects: Cohort born in 1972-3. Setting: Dunedin, New Zealand. Main outcome measure: Blood pressure at ages 9 and 18 years. Results: Compared with singletons, twins had a systolic blood pressure 4.55 (95% confidence interval 1.57 to 7.52) mm Hg lower at age 9 after adjustment for direct and indirect effects of sex, maternal smoking, mother's height, socioeconomic status, and birth weight, as well as concurrent height and body mass index. Blood pressure in children whose mothers had smoked during pregnancy was 1.54 (0.46 to 2.62) mm Hg higher than in those whose mothers did not. The total effect of birth weight on systolic blood pressure at age 9 was—0.78 —1.76 to 0.20) mm Hg and that for mother's height was 0.10 (0.06 to 0.14) mm Hg. Similar results were obtained for systolic blood pressure at age 18. The total effect of twins, maternal smoking, and birth weight on diastolic blood pressure was not significant at either age. Conclusions: Twins had lower birth weight and lower systolic blood pressure at ages 9 and 18 than singletons. This finding challenges the fetal origins hypothesis. The effect of maternal smoking was consistent with the fetal origin hypothesis in that the infants of smokers were smaller and had higher blood pressure at both ages. This may be explained by pharmacological rather than nutritional effects. The total effect of birth weight on systolic blood pressure, after its indirect effect working through concurrent measures of height and body mass index was taken into account, was small.
Depression Among Type 2 Diabetes Rural Appalachian Clinic Attendees
Authors: Mary de Groot, Todd Doyle, Erin Hockman, Charles Wheeler, Brenda Pinkerman, Jay Shubrook, Robert Gotfried, Frank Schwartz
Journal: Diabetes Care (2007)

The prevalence and impact of type 2 diabetes in Appalachia is understudied despite the presence of high-risk socioeconomic conditions (e.g., low levels of education and income). Appalachian counties experience greater burdens of poverty, income inequality, unemployment (1), and diabetes compared with non-Appalachian counties (2–5). Rates of comorbid depression have not been documented in this region.

Patients with type 2 diabetes are two times more likely to experience depressive symptoms than their peers without diabetes (6). Depression prevalence in studies using self-report depression inventories was found to be 32.9%, with lower rates (28.5%) observed in studies using diagnostic interview schedules (6,7). Depressive symptoms are associated with worsened blood glucose levels (8), diabetes complications (9), increased functional disability (10), worsened adherence to diabetes regimen (11), higher ambulatory care costs (12), and increased mortality (13).

The current study was conducted to identify rates of self-reported depression and to identify the socioeconomic and medical correlates of depression among type 2 diabetic patients attending family medicine and endocrinology appointments from rural Appalachian counties of southeastern Ohio and West Virginia. It was hypothesized that poverty would increase the risk of comorbid depression in this region.

Participants, recruited from family medicine and endocrinology practices, were diagnosed with type 2 diabetes for ≥1 year and aged ≥18 …
Airway proteins involved in bacterial clearance susceptible to cathepsin G proteolysis
Authors: M. M. Farberman, K. T. Akers, J. P. Malone, P. Erdman-Gilmore, R. R. Townsend, T. Ferkol
Journal: European Respiratory Journal (2009)

Serine proteases released from neutrophils are central to the pathogenesis of cystic fibrosis lung disease and are considered to be obvious therapeutic targets. Neutrophil elastase digests key opsonins present in the lung and disrupts phagocytosis, allowing bacteria to persist despite established pulmonary inflammation. We have found that cathepsin G, an abundant serine protease found in human and murine neutrophils, has other roles in the development of suppurative lung diseases. Murine models of endobronchial inflammation indicate that cathepsin G inhibits airway defences and interferes with the host's ability to clear Pseudomonas aeruginosa from the lung with effects distinct from neutrophil elastase. We hypothesise that differences in bacterial killing are due to defects in innate defences created by proteolysis. Protein profiles of bronchoalveolar lavage of infected wild-type and cathepsin G-deficient mice were compared using two-dimensional polyacrylamide gel electrophoresis and tandem mass spectrometry. Four proteins in bronchoalveolar lavage were cleaved by cathepsin G. Serum amyloid P component leaked into the lung during acute infection and was digested by cathepsin G. Its cleavage products had greater binding to lipopolysaccharide and interfered with phagocytosis. These results indicate that cleaved serum amyloid P component acts as an anti-opsonin and interferes with bacterial clearance from the lung.
Ras Mediates Effector Pathways Responsible for Pre-B Cell Survival, Which Is Essential for the Developmental Progression to the Late Pre-B Cell Stage
Authors: Hitoshi Nagaoka, Yoshimasa Takahashi, Reiko Hayashi, Tohru Nakamura, Kumiko Ishii, Junichiro Matsuda, Atsuo Ogura, Yumiko Shirakata, Hajime Karasuyama, Tetsuo Sudo, Shin-Ichi Nishikawa, Takeshi Tsubata, Tsuguo Mizuochi, Toshihiko Asano, Hitoshi Sakano, Toshitada Takemori
Journal: The Journal of Experimental Medicine (2000)

Ras is essential for the transition from early B cell precursors to the pro-B stage, and is considered to be involved in the signal cascade mediated by pre-B cell antigen receptors. To examine the role of p21(ras) in the late stage of B cell differentiation, we established transgenic mice (TG) expressing a dominant-inhibitory mutant of Ha-ras (Asn-17 Ha-ras) in B lineage cells at high levels after the early B cell precursor stage. Expression of p21(Asn-17) (Ha-ras) was associated with a prominent reduction in the number of late pre-B cells, but had little effect on proliferation of early pre-B cells. Inhibition of p21(ras) activity markedly reduced the life span of pre-B cells, due, at least in part, to downregulation of the expression of an antiapoptotic protein, Bcl-xL. Thus, the apparent role for p21(ras) activity in pre-B cell survival may explain the decreased numbers of late pre-B cells in Asn-17 Ha-ras TG. Consistent with this possibility, overexpression of Bcl-2 in Asn-17 Ha-ras TG reversed the reduction in the number of late pre-B cells undergoing immunoglobulin light chain gene (IgL) rearrangement and progressing to immature B cells. These results suggest that p21(ras) mediates effector pathways responsible for pre-B cell survival, which is essential for progression to the late pre-B and immature B stages.
Single Transmembrane Spanning Heterotrimeric G Protein-Coupled Receptors and Their Signaling Cascades
Authors: Tarun B. Patel
Journal: Pharmacological Reviews (2004)

Heptahelical of serpentine receptors such as the adrenergic receptors are well known to mediate their actions via heterotrimeric GTP-binding proteins. Likewise, receptors that traverse the cell membrane once have been shown to mediate their biological actions by activating several different mechanisms including stimulation of their intrinsic tyrosine kinase activities or the kinase activities of other proteins. Some of these single transmembrane receptors have an intrinsic guanylyl cyclase activity and can stimulate the cyclic GMP second messenger system; however, over the last few years, several studies have shown the involvement of heterotrimeric GTP-binding proteins in mediating signals that eventually culminate in the biological actions of single transmembrane spanning receptors and proteins. These receptors include the receptor tyrosine kinases that mediate the actions of growth factors such as epidermal growth factor, insulin, insulin-like growth factor as well as receptors for atrial natiuretic hormone or the zona pellucida protein (ZP3) and integrins. In this review, the significance of the coupling of the single transmembrane spanning receptors to G proteins has been highlighted by providing several examples of the concept that signaling via these receptors may involve the activation of multiple signaling cascades.
Optic Neuritis, A New Variant of Experimental Encephalomyelitis, A Durable Model for All Seasons, Now In Its Seventieth Year
Authors: Lawrence Steinman
Journal: The Journal of Experimental Medicine (2003)

One of the most enduring models of human disease now celebrates the seventieth anniversary of its publication in The Journal of Experimental Medicine . Thomas Rivers, working at the Hospital of the Rockefeller Institute for Medical Research, along with his colleagues D.H. Sprunt and G.P. Berry,
No impact of passive smoke on the somatic profile of lung cancers in never-smokers
Authors: Sébastien Couraud, Didier Debieuvre, Lionel Moreau, Patrick Dumont, Jacques Margery, Elisabeth Quoix, Bernard Duvert, Laurent Cellerin, Nathalie Baize, Bruno Taviot, Marie Coudurier, Jacques Cadranel, Pascale Missy, Franck Morin, Jean-François Mornex, Gérard Zalcman, Pierre-Jean Souquet
Journal: European Respiratory Journal (2015)

EGFR and HER2 mutations and ALK rearrangement are known to be related to lung cancer in never-smokers, while KRAS , BRAF and PIK3CA mutations are typically observed among smokers. There is still debate surrounding whether never-smokers exposed to passive smoke exhibit a “smoker-like” somatic profile compared with unexposed never-smokers. Passive smoke exposure was assessed in the French BioCAST/IFCT-1002 never-smoker lung cancer cohort and routine molecular profiles analyses were compiled. Of the 384 patients recruited into BioCAST, 319 were tested for at least one biomarker and provided data relating to passive smoking. Overall, 219 (66%) reported having been exposed to passive smoking. No significant difference was observed between mutation frequency and passive smoke exposure ( EGFR mutation: 46% in never exposed versus 41% in ever exposed; KRAS : 7% versus 7%; ALK : 13% versus 11%; HER2 : 4% versus 5%; BRAF : 6% versus 5%; PIK3CA : 4% versus 2%). We observed a nonsignificant trend for a negative association between EGFR mutation and cumulative duration of passive smoke exposure. No association was found for other biomarkers. There is no clear association between passive smoke exposure and somatic profile in lifelong, never-smoker lung cancer.
No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients.
Authors: J M Hansen, H Løkkegaard, C E Høy, N Fogh-Andersen, N V Olsen, S Strandgaard
Journal: Journal of the American Society of Nephrology (1995)

Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healthy volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium clearance, and urinary excretion of beta 2-microglobulin in any of the groups. The infusion of amino acids induced a comparable increase in GFR, lithium clearance, and the urinary excretion rate of beta 2-microglobulin in all three groups with no additional effect of fish oil. Thus, long-term renal transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.
Regulator spells out rules on disease awareness campaigns
Authors: T. Jackson
Journal: BMJ (2003)

What do drug companies do when the law prevents them from advertising prescription only medicines directly to the public? One answer might be that they instead advertise the disease, be it incontinence, impotence, or fungal nail infections.

While on the surface disease awareness campaigns (DACs), as they are known, appear to do no more than provide quality information to patients and public alike, concerns have been growing that the boundary between education and drug promotion has been getting increasingly blurred. Have DACs, which in themselves are not especially new, become one more step towards direct to consumer advertising of medicines?

Last month the Medicines and Health-care products Regulatory Agency (MHRA) issued guidelines on what drug companies can and cannot say …
A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians
Authors: Yoichiro Kamatani, Sukanya Wattanapokayakit, Hidenori Ochi, Takahisa Kawaguchi, Atsushi Takahashi, Naoya Hosono, Michiaki Kubo, Tatsuhiko Tsunoda, Naoyuki Kamatani, Hiromitsu Kumada, Aekkachai Puseenam, Thanyachai Sura, Yataro Daigo, Kazuaki Chayama, Wasun Chantratita, Yusuke Nakamura, Koichi Matsuda
Journal: Nature Genetics (2009)