tbuckley/cabot-search huggingface dataset:
Work of the Heart Under the Effect of Induced Arterial Pressure Oscillations Studied in Intact Anesthetized Dogs
Authors: HEINZ P. PIEPER
Journal: Circulation Research (1962)

The arterial system of intact anesthetized dogs and a physical model, which consisted of a "heart," an elastic "arterial" reservoir, and a "peripheral resistance," have both been studied in comparison. In both systems, the volume contained in the arterial reservoir was rhythmically altered by means of a slow sinusoidal piston pump which resulted in slow oscillations of the mean arterial pressure with the arterial pressure pulsations superimposed. It was found that in the physical model, the systolic pressure pulse was larger during the phase of rising pressure (increasing volume) than during the phase of falling pressure (decreasing volume), while in the animal the systolic pressure pulses were equal in either phase. The aortic pressure pulse of the animal was a linear function of the presystolic aortic pressure during pressure oscillation and independent of the induced volume alteration. Recordings of the stroke output of the heart revealed that the heart of the animal adjusted its output in such a manner that the induced systolic changes of the arterial contents were quantitatively compensated. The mechanism by which this is accomplished is of particular interest, since it would also enable the heart to compensate instantaneously for physiological alterations of the volume in the arterial system as caused by changes in peripheral runoff. This mechanism of instantaneous adjustment of the stroke output can be explained on the basis of Starling's Law of the Heart if the procedure of the calculation of the external work is modified.
Plasma Separation in Patients with Bronchial Asthma, Atopic Dermatitis and Hyperimmunoglobulinaemia E
Authors: H. Nielsen, B. Thomsen, R. Djurup, I. Søndergaard, E. Kappelgaard, A. Berkowicz, H. Kjersem, J. I. Dahlager, W. Szpirt, S. Ullman, N. H. Valerius, B. Weeke
Journal: Allergy (1984)

The effect of intensive plasma separation performed eight times within 5 weeks in four patients with atopic dermatitis, bronchial asthma and hyperimmunoglobulinaemia E was followed as regards clinical symptoms and changes in the concentrations of serum (S) IgE, S IgG, S IgA, S IgM, plasma complement C3 split products, S transferrin, blood eosinophils, chemotaxis of neutrophil cells and histamine metabolites in urine in samples obtained consecutively during the period of observation. The occurrence of circulating immune complexes (IC) was analysed by a polyclonal rheumatoid factor (pRF) agglutination inhibition assay and an IgE IC specific technique. IgE 1C were demonstrated in three of the patients prior to plasma separation, complexed IgE was 2–3 % of the total concentration of S IgE. In one patient complexes were detected by the pRF agglutination inhibition assay, also. In the three patients with IgE 1C, the complexes disappeared during treatment, but recurred in two of the patients shortly after the last plasma separation. Shortly after eight separations the S IgE was reduced in all patients to a mean level of 46% of the pre‐exchange concentrations. During the following 3 weeks the relative increase of S IgE in three of the patients was similar to the values obtained for S IgG. Serum IgG was subnormal in all patients during the period of treatment. Increasing numbers of eosinophils were observed in three of the patients after the fifth separation procedure. The histamine metabolite 1,4‐methylimidazoleacetic (1,4‐MIAA) in urine was increased in all patients, but no significant changes were observed during the treatment. The increase of complement C3c split product in two of the patients during the separation procedure indicated that complement activation took place. Questionable clinial improvement of dermatitis and asthma was observed during the period of plasma separation, and the effect was short lasting. For the time being plasma separation in patients with combined hyperimmunoglobulinaemia E, asthma and atopic dermatitis cannot be recommended as a tool in the management of the disease.
Peers vote to put mental health on equal footing with physical health in the NHS
Authors: Z. Kmietowicz
Journal: BMJ (2012)

The effects of MCI-154 (6-[4-(49-pyridyl)aminophenyl]-4,5-dihydro-3(2H)- pyridazinone hydrochloride.3H2O), a cardiotonic agent with calcium sensitizing actions, on regional contractile function and myocardial oxygen consumption (MVO2) were studied in the dog hearts with and without partial occlusion of the left anterior descending coronary artery and compared with those of dobutamine. Segment shortening by sonomicrometry, regional myocardial blood flow by microspheres and the oxygen content of coronary venous blood drawn from the ischemic left anterior descending coronary artery area were simultaneously measured. The ischemic zone segment shortening and left ventricular (LV) dP/dtmax were decreased after partial occlusion. The infusion of MCI-154 starting 20 min after ischemia improved the depressed segment shortening and LV dP/dtmax without increasing the ischemic zone MVO2 and regional myocardial blood flow. In the nonischemic hearts, MCI-154 did not increase MVO2 and coronary blood flow despite the augmentation of myocardial contractility. MCI-154 decreased LV end-diastolic pressure and systemic blood pressure. On the other hand, dobutamine failed to increase the ischemic zone segment shortening, but the drug increased MVO2, coronary blood flow and LV dP/dtmax in both ischemic and nonischemic hearts. These results indicate that MCI-154 alleviates the ischemic contractile failure without increasing myocardial oxygen demand. Thus, MCI-154 may be useful in the management of heart failure with reduced coronary reserve.
Bevacizumab Preconditioning Followed by Etoposide and Cisplatin Is Highly Effective in Treating Brain Metastases of Breast Cancer Progressing from Whole-Brain Radiotherapy
Authors: Yen-Shen Lu, Tom Wei-Wu Chen, Ching-Hung Lin, Dah-Cherng Yeh, Ling-Ming Tseng, Pei-Fang Wu, Kun-Ming Rau, Bang-Bin Chen, Ta-Chung Chao, Shu-Min Huang, Chiun-Sheng Huang, Tiffany Ting-Fang Shih, Ann-Lii Cheng
Journal: Clinical Cancer Research (2015)

Abstract Purpose: We hypothesized that a window period between bevacizumab and cytotoxic agents may enhance drug delivery into tumor tissue through bevacizumab-induced vascular normalization in patients with brain metastases of breast cancer (BMBC). Experimental Design: A single-arm phase II study was conducted in which BMBC patients refractory to whole-brain radiotherapy (WBRT) were enrolled. In a 21-day cycle, patients received bevacizumab (15 mg/kg) on day 1, which, with a 1-day window period, was followed by etoposide (70 mg/m2/day; days 2–4) and cisplatin (70 mg/m2; day 2; BEEP regimen). The BEEP regimen was administered for a maximum of 6 cycles. The primary endpoint was the central nervous system (CNS)–objective response rate according to volumetric response criteria. Results: A total of 35 patients were enrolled between January 2011 and January 2013. The median age was 54.3 years (range, 33–75); 19 patients (54.3%) had an Eastern Cooperative Oncology Group performance status of 2 or 3. Twenty-seven patients [77.1%; 95% confidence interval (CI), 59.9–89.6] achieved a CNS-objective response, including 13 patients (37.1%) with a ≥80% volumetric reduction of CNS lesions. With a median follow-up of 16.1 months, the median CNS progression-free survival and overall survival times were 7.3 months (95% CI, 6.5–8.1) and 10.5 months (95% CI, 7.8–13.2), respectively. Common grade 3 or 4 toxicities included neutropenia (30.8%) and infection (21.3%). Conclusions: By administering bevacizumab 1 day before etoposide and cisplatin, the BEEP regimen appeared highly effective in BMBC refractory to WBRT. Further study of vascular normalization window concept is warranted. Clin Cancer Res; 21(8); 1851–8. ©2015 AACR.
Hypopyon in Patients with Uveitis
Authors: Ali A. Zaidi, Gui-Shuang Ying, Ebenezer Daniel, Sapna Gangaputra, James T. Rosenbaum, Eric B. Suhler, Jennifer E. Thorne, C. Stephen Foster, Douglas A. Jabs, Grace A. Levy-Clarke, Robert B. Nussenblatt, John H. Kempen
Journal: Ophthalmology (2009)
Effects of Digoxin on Morbidity and Mortality in Diastolic Heart Failure
Authors: Ali Ahmed, Michael W. Rich, Jerome L. Fleg, Michael R. Zile, James B. Young, Dalane W. Kitzman, Thomas E. Love, Wilbert S. Aronow, Kirkwood F. Adams, Mihai Gheorghiade
Journal: Circulation (2006)

Background— About half of the 5 million heart failure patients in the United States have diastolic heart failure (clinical heart failure with normal or near-normal ejection fraction). Except for candesartan, no drugs have been tested in randomized clinical trials in these patients. Although digoxin was tested in an appreciable number of diastolic heart failure patients in the Digitalis Investigation Group ancillary trial, detailed findings from this important study have not previously been published. Methods and Results— Ambulatory chronic heart failure patients (n=988) with normal sinus rhythm and ejection fraction &gt;45% (median, 53%) from the United States and Canada (1991 to 1993) were randomly assigned to digoxin (n=492) or placebo (n=496). During follow-up with a mean length of 37 months, 102 patients (21%) in the digoxin group and 119 patients (24%) in the placebo group (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.63 to 1.07; P =0.136) experienced the primary combined outcome of heart failure hospitalization or heart failure mortality. Digoxin had no effect on all-cause or cause-specific mortality or on all-cause or cardiovascular hospitalization. Use of digoxin was associated with a trend toward a reduction in hospitalizations resulting from worsening heart failure (HR, 0.79; 95% CI, 0.59 to 1.04; P =0.094) but also a trend toward an increase in hospitalizations for unstable angina (HR, 1.37; 95% CI, 0.99 to 1.91; P =0.061). Conclusions— In ambulatory patients with chronic mild to moderate diastolic heart failure and normal sinus rhythm receiving angiotensin-converting enzyme inhibitor and diuretics, digoxin had no effect on natural history end points such as mortality and all-cause or cardiovascular hospitalizations.
Impact of Farnesylation Inhibitors on Survival in Hutchinson-Gilford Progeria Syndrome
Authors: Leslie B. Gordon, Joe Massaro, Ralph B. D’Agostino, Susan E. Campbell, Joan Brazier, W. Ted Brown, Monica E. Kleinman, Mark W. Kieran
Journal: Circulation (2014)

Background— Hutchinson-Gilford progeria syndrome is an ultrarare segmental premature aging disease resulting in early death from heart attack or stroke. There is no approved treatment, but starting in 2007, several recent single-arm clinical trials administered inhibitors of protein farnesylation aimed at reducing toxicity of the disease-producing protein progerin. No study assessed whether treatments influence patient survival. The key elements necessary for this analysis are a robust natural history of survival and comparison with a sufficiently large patient population that has been treated for a sufficient time period with disease-targeting medications. Methods and Results— We generated Kaplan–Meier survival analyses for the largest untreated Hutchinson-Gilford progeria syndrome cohort to date. Mean survival was 14.6 years. Comparing survival for treated versus age- and sex-matched untreated cohorts, hazard ratio was 0.13 (95% confidence interval, 0.04–0.37; P &lt;0.001) with median follow-up of 5.3 years from time of treatment initiation. There were 21 of 43 deaths in untreated versus 5 of 43 deaths among treated subjects. Treatment increased mean survival by 1.6 years. Conclusions— This study provides a robust untreated disease survival profile that can be used for comparisons now and in the future to assess changes in survival with treatments for Hutchinson-Gilford progeria syndrome. The current comparisons estimating increased survival with protein farnesylation inhibitors provide the first evidence of treatments influencing survival for this fatal disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique Indentifiers: NCT00425607, NCT00879034, and NCT00916747.
Drug Use in Psychiatric Disorders of Children
Authors: BARBARA FISH
Journal: American Journal of Psychiatry (1968)

Drugs are equally important in the treatment of disturbed children as in the treatment of adults. Drug therapy modifies appropriate target symptoms and facilitates the other aspects of treatment. Specific indications and limitations are discussed, as well as the ways in which children's responses to major and minor tranquilizers and stimulanis differ from responses of adults.
A model for British medical education.
Authors: S Lowry
Journal: BMJ (1993)

tion of the avoidable factor to the death; at best they can suggest that it was an associated factor.Nevertheless the inquiry by Payne and colleagues managed to uncover a number of deaths that might have been prevented given competent practice.It should return to the problem after a year or two to determine whether the number ofthese sentinel events has fallen.Inquiry into such events in young people should certainly be encouraged, and mechanisms should be developed to allow the incorporation of audit methods into the contracting process.
Interleukin 5 Is Protective during Sepsis in an Eosinophil-Independent Manner
Authors: Stefanie N. Linch, Erin T. Danielson, Ann M. Kelly, Raina A. Tamakawa, James J. Lee, Jeffrey A. Gold
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The immune response in sepsis is characterized by overt immune dysfunction. Studies indicate immunostimulation represents a viable therapy for patients. One study suggests a potentially protective role for interleukin 5 (IL-5) in sepsis; however, the loss of eosinophils in this disease presents a paradox.To assess the protective and eosinophil-independent effects of IL-5 in sepsis.We assessed the effects of IL-5 administration on survival, bacterial burden, and cytokine production after polymicrobial sepsis. In addition, we examined the effects on macrophage phagocytosis and survival using fluorescence microscopy and flow cytometry.Loss of IL-5 increased mortality and tissue damage in the lung, IL-6 and IL-10 production, and bacterial burden during sepsis. Therapeutic administration of IL-5 improved mortality in sepsis. Interestingly, IL-5 administration resulted in neutrophil recruitment in vivo. IL-5 overexpression in the absence of eosinophils resulted in decreased mortality from sepsis and increased circulating neutrophils and monocytes, suggesting their importance in the protective effects of IL-5. Furthermore, novel data demonstrate IL-5 receptor expression on neutrophils and monocytes in sepsis. IL-5 augmented cytokine secretion, activation, phagocytosis, and survival of macrophages. Importantly, macrophage depletion before the onset of sepsis eliminated IL-5-mediated protection. The protective effects of IL-5 were confirmed in humans, where IL-5 levels were elevated in patients with sepsis. Moreover, neutrophils and monocytes from patients expressed the IL-5 receptor.Taken together, these data support a novel role for IL-5 on noneosinophilic myeloid populations, and suggest treatment with IL-5 may be a viable therapy for sepsis.
Coagulation abnormalities in patients with Gaucher's disease: Effect of therapy
Authors: H.H. Billett, S. Rizvi, A. Sawitsky
Journal: American Journal of Hematology (1996)

Various coagulation defects have been associated with Gaucher's disease, including factor IX deficiency and acquired von Willebrand's disease (VWD). We performed repeated coagulation assays in 9 patients with Gaucher's disease over a period of 2 years. The prothrombin time (PT) and fibrinogen levels were normal in 8 of 9 patients, while the partial thromboplastin time (PTT) was abnormal in 5 of 9; all mixing PTT tests showed correction. Factor IX was normal repeatedly in the 7 of 7 patients tested. In contrast, factor XI was decreased in 3 of 9 patients assayed. Anticardiolipin (ACL) IgM was normal in all patients. ACL IgG was highly variable; levels were abnormal at least once in 6 of 8 patients, but were also normal at least once in 7 of 8 patients. Factor VIII was also quite variable: levels were decreased at least once in 4 of 9 patients, and normal at least once in 8 of 9 patients. Von Willebrand factor antigen (VWF Ag) studies were normal in 7 of 8 patients, but VWF activity was decreased at least once in 4 of 8 patients. In some patients, these problems could be overcome by specimen dilution. In only 1 patient was VWF Ag decreased; this patient had a factor VIIIC level of 13%, and VWF activity of 18.7%. Coagulation assays performed before and after alglucerase administration failed to demonstrate any significant improvement in these assays, and neither was there a consistent improvement over the duration of therapy. We suggest that previously reported decreases in factor IX and VWF may be secondary to the interfering presence of increased cerebroside levels. Caution must be used in the interpretation of clotting assays in the patient with Gaucher's disease. © 1996 Wiley-Liss, Inc.
On Measuring “Quality” Health Care: Beyond the Hospital
Authors: R.H. Egdahl, Cynthia H. Taft
Journal: New England Journal of Medicine (1976)

Although the term "quality" is increasingly being used as an adjective in relation to health care, no adequate definition of quality is agreed upon: the definition chosen varies according to the perspective of the viewer, whether patient, physician or administrator. Nevertheless, in the name of "quality" two general types of procedures are being developed and widely applied to health-care systems. Despite some overlap, these procedures are intrinsically driven by quite different motives.One set of procedures — called "concurrent review" — has the clear-cut goal of cost containment and centers around controlling the utilization of hospital beds. Admission certification, continued . . .
Abstract 402: Plasticity of tumor associated macrophages in a metastatic melanoma model in the mouse
Authors: Annamaria Gal, Thomas T. Tapmeier, Ruth J. Muschel
Journal: Cancer Research (2012)

Abstract Macrophages acquire different functional traits, with the pro-inflammatory, classically activated M1 and the tissue-repair, alternatively activated M2 phenotypes the best characterized to date. Tumor-associated macrophages (TAMs) have been described as alternatively activated and exert pro-tumoral activity. We investigated TAMs isolated from subcutaneous tumors and experimental lung metastases at an early (72 h) and late (3 wk) stage within a B16F10 mouse melanoma model. The macrophages were characterized according to their expression of genes, surface markers and secreted factors. Interestingly, the mRNA profile revealed both M1- and M2-associated gene expression in macrophages derived from s.c. melanoma, including Cxcl9, Cxcl11, Il-1a, Nos2, and Retnla (FIZZ-1), Arg-1 and Fn1, respectively. In early pulmonary metastases, we found that macrophages also expressed both pro-inflammatory (Il1b, Il12b, Ccl2), and anti-inflammatory (Ccl17 and Ccl22) cytokines and chemokines and other M1- and M2-associated genes, such as Cd40, Cd86, and Il27ra and Itgax (Cdd11c), respectively. Macrophages from late stage lung metastases displayed predominantly alternatively activated characteristics with Arg1, Retnla and Fn1 expression, but pro-inflammatory genes, such as Ccl2, Il1b and Cxcl10 were also induced/upregulated. We therefore suggest an intermediate phenotype of TAMs which does not fit the orthodox M1/M2 paradigm. To describe the mechanism by which macrophages are recruited to pulmonary metastases, we investigated chemokine receptor expression of macrophages infiltrating the lung. While Ccr2 was expressed at high level in macrophages associated with both the control and B16F10 metastases bearing lung, we found that Ccr1 and Ccr5 expression was induced after tumor cell challenge. The secretion profile of B16F10 cells revealed CCL5 (RANTES), a ligand for these receptors, secreted at high level, which suggests that CCL5 attracts macrophages to lung metastases via CCR1 and CCR5. The effect of anti-CCL5 antibody treatment, and s.c melanoma growth and pulmonary metastasis development in CCR1-/- and CCR5-/- mice will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 402. doi:1538-7445.AM2012-402
Mechanisms of tissue inhibitor of metalloproteinase 1 augmentation by IL-13 on TGF-β1–stimulated primary human fibroblasts
Authors: Xiuxia Zhou, Haizhen Hu, Mai-Lan N. Huynh, Chakradhar Kotaru, Silvana Balzar, John B. Trudeau, Sally E. Wenzel
Journal: Journal of Allergy and Clinical Immunology (2007)
A National Study of Medical and Surgical Specialties
Authors: Robert C. Mendenhall
Journal: JAMA (1978)

The University of Southern California is conducting a national survey of physicians involving the collection and analysis of detailed data on the activities and practice characteristics of generalists, medical specialists, and surgical specialists of different types. This is the first of a series of reports on the survey and provides an overview of the survey's background, purposes, and general research methods. Basic features of the research methods include the development of a survey instrument capable of obtaining different types of practice data from physicians in most specialties and practice arrangements, the sampling of physician population to ensure that sufficient data are obtained from physicians in most specialties and practice arrangements, and the creation and application of a scheme for classifying patient-care services provided by physicians along dimensions related to primary care.
Challenges in managing dyspepsia in general practice
Authors: L. Agreus, N. Talley
Journal: BMJ (1997)

Although dyspepsia has many possible causes, the primary causes are peptic ulcer disease, gastro-oesophageal reflux disease, and functional (non-ulcer dyspepsia). General practitioners managing dyspepsia face several dilemmas.

#### Summary points

Subgrouping of symptoms should not guide empirical treatment of dyspepsia

Symptoms of underlying serious disease and use of non-steroidal anti-inflammatory drugs are indications for prompt endoscopy

A breath test is superior to a blood test in documenting H pylori infection and guiding the management of dyspepsia in general practice

Empirical treatment with acid reducing or prokinetic drugs for all patients with dyspepsia is inappropriate as peptic ulcer disease will be inadequately treated

Empirical eradication treatment of H pylori in patients with dyspepsia who are positive for the organism is preferable to other empirical treatment if prompt endoscopy is not an option

### Dyspepsia subgroups: an irrelevant concept

Broad (and vague) definitions of dyspepsia have been proposed,1 but a current internationally accepted definition of dyspepsia is chronic or recurrent pain or discomfort centred on the upper abdomen.2 People with heartburn or acid regurgitation alone and those in whom reflux symptoms are dominant and epigastric pain or discomfort is minor should probably not be classed as having dyspepsia but as having symptomatic gastro-oesophageal reflux disease. The same applies to patients who have a disturbed bowel habit and dyspeptic symptoms, which should be classed as the irritable bowel syndrome.2

### Dyspepsia subgroups

During the past decade dyspepsia has been divided into clinical subgroups based on medical history: ulcer-like (typical ulcer symptoms), dysmotility-like (symptoms suggestive of gastric stasis), reflux-like (retrosternal and concomitant upper abdominal symptoms), and unspecified (symptoms cannot be classified) (box). …