tbuckley/cabot-search huggingface dataset:
Severe Community-acquired Pneumonia
Authors: MAURICIO RUIZ, SANTIAGO EWIG, ANTONI TORRES, FRANCISCO ARANCIBIA, FRANCESC MARCO, JOSEP MENSA, MIGUEL SANCHEZ, JOSE ANTONIO MARTINEZ
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The aim of the study was to determine risk factors for severe community-acquired pneumonia (CAP) as well as to compare microbial patterns of severe CAP to a previous study from our respiratory intensive care unit (ICU) originating from 1984 to 1987. Patients admitted to the ICU according to clinical judgment were defined as having severe CAP. For the study of risk factors, a hospital-based case-control design was used, matching each patient with severe CAP to a patient hospitalized with CAP but not requiring ICU admission. Microbial investigation included noninvasive and invasive techniques. Overall, 89 patients with severe CAP were successfully matched to a control patient. The presence of an alcohol ingestion of ⩾ 80 g/d (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.4 to 10.6, p = 0.008) was found to be an independent risk factor for severe CAP and prior ambulatory antimicrobial treatment (OR 0.37, 95% CI 0.17 to 0.79, p = 0.009) to be protective. Streptococcus pneumoniae (24%) continued to be the most frequent pathogen; however, 48% of strains were drug-resistant. “Atypical” bacterial pathogens were significantly more common (17% versus 6%, p = 0.006) and Legionella spp. less common (2% versus 14%, p = 0.004) than in our previous study, whereas gram-negative enteric bacilli (GNEB) and Pseudomonas aeruginosa continued to represent important pathogens (6% and 5%, respectively). Our findings provide additional evidence for the importance of the initiation of early empiric antimicrobial treatment for a favorable outcome of CAP. Variations of microbial patterns are only in part due to different epidemiological settings. Therefore, initial empiric antimicrobial treatment will also have to take into account local trends of changing microbial patterns.
Delivery of radiofrequency energy to the lower oesophageal sphincter and gastric cardia inhibits transient lower oesophageal sphincter relaxations and gastro-oesophageal reflux in patients with reflux disease
Authors: W C E Tam
Journal: Gut (2003)

<b>Background and aims:</b> Radiofrequency energy (RFe) treatment to the lower oesophageal sphincter (LOS) and gastric cardia is a new luminally delivered therapy proposed as an alternative treatment for gastro-oesophageal reflux disease (GORD). However, it is unclear how RFe achieves its antireflux effect. This study investigated the effects of RFe on mechanisms of spontaneous reflux in patients with GORD. <b>Methods:</b> Twenty patients with GORD underwent endoscopy, symptom evaluation, and combined postprandial oesophageal manometry and pH monitoring before and six months after RFe, and 24 hour ambulatory pH monitoring before and at six and 12 months after treatment. <b>Results:</b> RFe reduced the rate of postprandial transient LOS relaxations from 6.8 (5.7–8.1) (median (interquartile range) per hour to 5.2 (4.2–5.8) per hour (p&lt;0.01), and increased mean basal LOS pressure from 5.2 (SEM 0.3) mm Hg to 8.0 (SEM 0.4) mm Hg (p&lt;0.01). The number of reflux events was reduced from 10 (2–15.3)/3 hours to 5 (3.5–8.5)/3 hours (p&lt;0.05) and there was an associated significant reduction in acid exposure time from 5.4% (0.4–14.7) to 3.9% (0.4–6.6) (p&lt;0.05). RFe significantly reduced ambulatory oesophageal acid exposure from 10.6% (7.8–13.0) to 6.8% (3.1–9.1) (p&lt;0.01) at six months and 6.3% (4.7–10.9) (p&lt;0.05) at 12 months. All patients required acid suppressant medication for symptom control before RFe. Six months after treatment, 15 patients (75%) were in symptomatic remission and 13 (65%) at 12 months. <b>Conclusions:</b> RFe has significant effects on LOS function that are associated with improvement in the antireflux barrier. Uncontrolled clinical data also suggest a beneficial effect in the control of reflux symptoms in these patients.
Effects of diuretics on inner medullary hemodynamics in the dog.
Authors: S Spitalewitz, S Y Chou, P F Faubert, J G Porush
Journal: Circulation Research (1982)

Although the hemodynamic effects of diuretics have been studied extensively, their effects on inner medullary blood flow remain unknown. In the present study, renal hemodynamics, including papillary plasma flow measured by the albumin accumulation technique, and associated alterations in papillary tissue solute content were determined in anesthetized, hydropenic dogs and during euvolemic diuresis induced by furosemide (3 mg/kg plus 2 mg/kg per hr, iv), ethacrynic acid (3 mg/kg plus 2 mg/kg per hr, iv) or chlorothiazide (10 mg/kg plus 10 mg/kg per hr, iv). Renal blood flow increased significantly after furosemide and ethacrynic acid and decreased significantly after chlorothiazide. Sixty minutes after diuretic administration, papillary plasma flow was 10.8 +/- 1.0 (mean +/- SE) in six furosemide- and 11.3 +/- 2.6 ml/min per 100 g in six ethacrynic acid-treated dogs, both significantly lower than in eight normal or eight chlorothiazide-treated dogs [26.4 +/- 2.6 and 26.7 +/- 2.7 ml/min per 100 g, respectively (P less than 0.01)]. A similarly low papillary plasma flow was also noted 10 minutes after diuretic administration in five furosemide and four ethacrynic acid dogs (13.6 +/- 2.3 and 13.4 +/- 1.8 ml/min per 100 g, respectively). In furosemide and ethacrynic acid dogs, papillary osmolality and sodium content were significantly lower than those in normal or chlorothiazide dogs. In normal and chlorothiazide dogs, papillary sodium content was similar, with a significantly reduced papillary osmolality in the latter. At the time papillary plasma flow was measured, extracellular fluid volume was similar among the four groups of dogs; however, plasma renin activity increased significantly in furosemide and ethacrynic acid dogs (P less than 0.01) and remained unchanged in normal and chlorothiazide dogs. Furthermore, papillary plasma flow was restored to normal (25.3 +/- 3.9 ml/min per 100 g) in five dogs in which furosemide was infused during angiotensin II blockage with saralasin, despite a similar diuresis and natriuresis as the other furosemide group. These data demonstrate that after administration of furosemide, ethacrynic acid and chlorothiazide, regulation of papillary plasma flow is independent of renal blood flow, and suggest that angiotensin II may play a role in the reduced papillary plasma flow in furosemide and ethacrynic acid dogs.
Gastro-oesophageal reflux symptoms, oesophagitis and Barrett's oesophagus in the general population: the Loiano-Monghidoro study
Authors: R M Zagari, L Fuccio, M-A Wallander, S Johansson, R Fiocca, S Casanova, B Y Farahmand, C C Winchester, E Roda, F Bazzoli
Journal: Gut (2008)

<h3>Objective:</h3> Existing endoscopy-based data on gastro-oesophageal reflux disease (GORD) in the general population are scarce. This study aimed to evaluate typical symptoms and complications of GORD, and their associated risk factors, in a representative sample of the Italian population. <h3>Methods:</h3> 1533 adults from two Italian villages were approached to undergo symptom assessment using a validated questionnaire and upper gastrointestinal endoscopy. Data were obtained from 1033 individuals (67.4% response rate). <h3>Results:</h3> The prevalence of reflux symptoms was 44.3%; 23.7% of the population experienced such symptoms on at least 2 days per week (frequent symptoms). The prevalence rates of oesophagitis and Barrett’s oesophagus in the population were 11.8% and 1.3%, respectively. Both frequent (relative risk (RR) 2.6; 95% confidence interval (CI) 1.7 to 3.9) and infrequent (RR 1.9; 95% CI 1.2 to 3.0) reflux symptoms were associated with the presence of oesophagitis. No reflux symptoms were reported by 32.8% of individuals with oesophagitis and 46.2% of those with Barrett’s oesophagus. Hiatus hernia was associated with frequent reflux symptoms and oesophagitis, and was present in 76.9% of those with Barrett’s oesophagus. We found no association between body mass index and reflux symptoms or oesophagitis. <h3>Conclusions:</h3> GORD is common in Italy, but the prevalence of Barrett’s oesophagus in the community is lower than has been reported in selected populations. Both frequent and infrequent reflux symptoms are associated with an increased risk of oesophagitis. Individuals with oesophagitis and Barrett’s oesophagus often have no reflux symptoms.
The Long-Term Effect of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia
Authors: John D. McConnell, Claus G. Roehrborn, Oliver M. Bautista, Gerald L. Andriole, Christopher M. Dixon, John W. Kusek, Herbert Lepor, Kevin T. McVary, Leroy M. Nyberg, Harry S. Clarke, E. David Crawford, Ananias Diokno, John P. Foley, Harris E. Foster, Stephen C. Jacobs, Steven A. Kaplan, Karl J. Kreder, Michael M. Lieber, M. Scott Lucia, Gary J. Miller, Mani Menon, Douglas F. Milam, Joe W. Ramsdell, Noah S. Schenkman, Kevin M. Slawin, Joseph A. Smith
Journal: New England Journal of Medicine (2003)

Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown.We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia.The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone.Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.
Recommendations for standardization of clinical trials with Allergen Specific Immunotherapy for respiratory allergy. A statement of a World Allergy Organization (WAO) taskforce
Authors: G. W. Canonica, C. E. Baena‐Cagnani, J. Bousquet, P. J. Bousquet, R. F. Lockey, H.‐J. Malling, G. Passalacqua, P. Potter, E. Valovirta
Journal: Allergy (2007)

Specific Immunotherapy for respiratory allergy is used since about one century and there is now solid documentation of its efficacy. Nevertheless, the methods and experimental designs used in clinical trials are quite heterogeneous and there is no unanimously accepted methodological standard. Many studies are planned with study designs that may not confirm the clinical value of SIT as an effective treatment to reduce disease severity. To ensure that patients are treated based on sound scientific evidence and to minimize the risk of misusing limited financial resources for scientific studies, the World Allergy Organization (WAO) convened a group of experts to provide guidelines for the methodology of future immunotherapy studies. This document summarizes the recommendations for study design, patients’ selection, appropriate outcomes and statistical treatment to be used in planning and performing clinical trials with specific immunotherapy.
Neoadjuvant Chemotherapy for Disseminated Colorectal Cancer: Changing the Paradigm
Authors: Lawrence Leichman
Journal: Journal of Clinical Oncology (2006)

Theoretical arguments for neoadjuvant systemic therapy before definitive surgery or radiation are well known and frequently articulated.The most compelling of these include treating undetected distant microscopic metastases as early as possible and downstaging tumors to allow for less radical, even organ-sparing, surgery without sacrificing overall survival (OS) or cure.Proofs of efficacy for neoadjuvant therapy include hard end points such as improved OS and increased cure rates.Because determination of cure rates and OS may take years, surrogate end points have been sought.In the clinic, the first measurement of efficacy is usually radiographic response.However, radiographic responses of solid tumors are poor surrogates for prognosis, whereas pathologic response, especially pathologic complete response (pCR), has been far more valuable in determining OS and cure after neoadjuvant therapy. 1 To date, most neoadjuvant solid tumor therapy has concentrated on the response of the primary tumor in relation to longterm outcome for patients with breast, esophageal, head and neck, gastric, and rectal cancers.The impact of systemic neoadjuvant chemotherapy on metastatic disease before surgery has received far less investigative attention.Nevertheless, as more effective systemic therapy in disseminated colorectal cancer 2 has been married to improved techniques in liver surgery, 3 many clinicians and investigators consider neoadjuvant systemic therapy to be appropriate for patients with metastases to the liver. 4,5The popularity of this practice, in the absence of class I clinical evidence, apparently triggered a recent cautionary note by experts in this field. 6 In this issue, Benoist et al 7 report a prospective clinical trial designed to "determine the significance" (their words) of increasingly important surgical and biologic questions after "seemingly effective" (my words) neoadjuvant chemotherapy in colorectal cancer patients with isolated liver metastases.They used radiographic response of specific liver lesions to define which patients were included in this study.Their questions included what percentage of predetermined surgically resectable liver metastases with complete radiographic response (cRR) actually have no cancer in the resected specimen (pCR), were these patients cured, and can a cRR in a surgically inaccessible lesion convert an inoperable patient to one who may be operable for cure if the cRR lesion remains in the liver. 7 From 1998 to 2004, Benoist et al 7 prospectively evaluated 586 consecutive patients treated at their institution for liver metastases from colorectal cancer and identified a cohort of 38 patients (6%) with liver-only metastatic colorectal cancer who also had no pre-
The Future of Polycystic Kidney Disease Research—As Seen By the 12 Kaplan Awardees
Authors: Corinne Antignac, James P. Calvet, Gregory G. Germino, Jared J. Grantham, Lisa M. Guay-Woodford, Peter C. Harris, Friedhelm Hildebrandt, Dorien J.M. Peters, Stefan Somlo, Vicente E. Torres, Gerd Walz, Jing Zhou, Alan S.L. Yu
Journal: Journal of the American Society of Nephrology (2015)

Polycystic kidney disease (PKD) is one of the most common life-threatening genetic diseases. Jared J. Grantham, M.D., has done more than any other individual to promote PKD research around the world. However, despite decades of investigation there is still no approved therapy for PKD in the United States. In May 2014, the University of Kansas Medical Center hosted a symposium in Kansas City honoring the occasion of Dr. Grantham's retirement and invited all the awardees of the Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease to participate in a forward-thinking and interactive forum focused on future directions and innovations in PKD research. This article summarizes the contributions of the 12 Kaplan awardees and their vision for the future of PKD research.
A phase I–II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer
Authors: C. Aschele, M.L. Friso, S. Pucciarelli, S. Lonardi, L. Sartor, G. Fabris, E.D.L. Urso, P. Del Bianco, G. Sotti, M. Lise, S. Monfardini
Journal: Annals of Oncology (2005)
Gene expression of the cardiac Na(+)-Ca2+ exchanger in end-stage human heart failure.
Authors: R Studer, H Reinecke, J Bilger, T Eschenhagen, M Böhm, G Hasenfuss, H Just, J Holtz, H Drexler
Journal: Circulation Research (1994)

The regulation of cytosolic Ca2+ concentration during excitation-contraction coupling is altered in the failing human heart. Previous studies have focused on disturbances in Ca2+ release and reuptake from the sarcoplasmic reticulum (SR), whereas functional studies of the cardiac Na(+)-Ca2+ exchanger, another important determinant of myocyte homeostasis, are lacking for the failing human heart. Using a cardiac Na(+)-Ca2+ exchanger cDNA recently cloned from a guinea pig cDNA library, we investigated the gene expression of the cardiac Na(+)-Ca2+ exchanger in relation to the SR Ca(2+)-ATPase. Expression of both genes was quantified in left ventricular myocardium from 24 failing human cardiac explants and 7 control heart samples in relation to beta-myosin heavy chain mRNA by slot blot analysis. Compared with patients with nonfailing hearts, patients with dilated cardiomyopathy (DCM, n = 13) showed a 55% increase in Na(+)-Ca2+ exchanger mRNA levels (P < .05 versus control value) and a 41% increase in patients with coronary artery disease (CAD, n = 11). In the same hearts, SR Ca(2+)-ATPase mRNA levels were decreased by 50% in DCM and by 45% in CAD (P < .05 for both versus control value). There was a positive correlation between Na(+)-Ca2+ exchanger and SR Ca(2+)-ATPase mRNA levels both in normal and failing human hearts, albeit with different slopes and intercepts of the regression line. The Na(+)-Ca2+ exchanger protein levels as assessed by Western blot analysis and normalized to beta-myosin heavy chain protein were increased in DCM and CAD (P < .05 and P < .01 versus control value, respectively), whereas SR Ca(2+)-ATPase protein levels were reduced (P < .05 for both groups versus control values). Thus, the Na(+)-Ca2+ exchanger gene expression is enhanced in failing human hearts and may, in part, compensate for the depressed SR function with regard to diastolic Ca2+ removal.
Form and function in religious signaling under pathogen stress
Authors: Paul Swartwout, Benjamin Grant Purzycki, Richard Sosis
Journal: Behavioral and Brain Sciences (2012)

Abstract The evolution of religious traditions may be partially explained by out-group avoidance due to pathogen stress. However, many religious rituals may increase rather than decrease performers' susceptibility to infection. Moreover, religions often spread through proselytizing, which requires out-group interaction; and in other cases, the benefits of economic exchange increase religious pluralism and social interactions with out-groups.
The cultural parameters of lead poisoning: a medical anthropologist's view of intervention in environmental lead exposure.
Authors: R T Trotter
Journal: Environmental Health Perspectives (1990)

This article identifies four culturally shaped sources of lead exposure in human societies: modern and historic technological sources: food habits; culturally defined health beliefs; and beauty practices. Examples of these potential sources of lead poisoning are presented from current cultures. They include the use of lead-glazed cooking pottery in Mexican-American households; folk medical use of lead in Hispanic, Arabic, South Asian, Chinese, and Hmong communities; as well as the use of lead as a cosmetic in the Near East, Southeast Asia, and South Asia. Four interacting cultural conditions that create barriers to the reduction of lead exposure and lead poisoning are identified and discussed. These are knowledge deficiencies, communication resistance, cultural reinterpretations, and incongruity of explanatory models.
Accuracy of Family History of Hemochromatosis or Iron Overload: The Hemochromatosis and Iron Overload Screening Study
Authors: R ACTON, J BARTON, L PASSMORE, P ADAMS, G MCLAREN, C LEIENDECKERFOSTER, M SPEECHLEY, E HARRIS, O CASTRO, J REISS
Journal: Clinical Gastroenterology and Hepatology (2008)
Intermittent administration of iron and sulfadoxine-pyrimethamine to control anaemia in Kenyan children: a randomised controlled trial
Authors: Hans Verhoef, Clive E West, Silas M Nzyuko, Stefan de Vogel, Rikkert van der Valk, Mike A Wanga, Anneleen Kuijsten, Jacobien Veenemans, Frans J Kok
Journal: The Lancet (2002)
Heme oxygenase–carbon monoxide signalling pathway in atherosclerosis: anti-atherogenic actions of bilirubin and carbon monoxide?
Authors: R Siow
Journal: Cardiovascular Research (1999)

Atherosclerosis is a major contributor to cardiovascular disease, and genetic disorders of lipoprotein metabolism are recognized risk factors in atherogenesis. The gaseous monoxides nitric oxide (NO) and carbon monoxide (CO), generated within the blood vessel wall, have been identified as important cellular messengers involved in the regulation of vascular smooth muscle tone. Microsomal heme oxygenases degrade heme to biliverdin and CO, and the cytosolic enzyme biliverdin reductase then catalyzes reduction of biliverdin to bilirubin, both powerful chain-breaking antioxidants. Two principal isozymes of heme oxygenase have been identified, a constitutive isoform HO-2 (Mr∼34 000) and an inducible isoform HO-1 (Mr∼32 000), which is expressed at a low basal level in vascular endothelial and smooth muscle cells and is induced by heavy metals, oxidative stress, inflammatory mediators and oxidized low density lipoproteins. Although NO and CO modulate intracellular cGMP levels, platelet aggregation and smooth muscle relaxation, CO has a much lower affinity for soluble guanylyl cyclase than NO. Decreased production or sensitivity to NO in atherosclerosis may be compensated for by an induction of HO-1, with bilirubin acting as a cellular antioxidant and CO as a vasodilator. This review examines the evidence that oxidized low density lipoproteins (LDL), hypoxia and pro-inflammatory cytokines induce HO-1 expression and activity in vascular endothelial and smooth muscle cells, and evaluates the anti-atherogenic potential of the heme oxygenase signalling pathway.