tbuckley/cabot-search huggingface dataset:
TRANSFERENCE OF INGUINAL GLANDS IN HUMAN SYPHILIS
Authors: C. J. LUNSFORD
Journal: JAMA (1934)

During the last decade a great deal of work has been done in intratesticular inoculation of rabbits with material from human lymph nodes infected with Spirochaeta pallida. Brown and Pearce<sup>1</sup>and Eberson,<sup>2</sup>among others, in their work with experimental animals established the fact that Spirochaeta pallida has a predilection for lymphoid tissue and rapidly disseminates therein. Engman and Eberson<sup>3</sup>studied the problem of infectivity in fifteen cases of latent syphilis and demonstrated the presence of Spirochaeta pallida in 20 per cent of the inguinal glands transplanted. Chesney and Kemp,<sup>4</sup>in an attempt to utilize the method as a biologic criterion of cure in cases of three thoroughly treated patients with early syphilis, obtained completely negative results in all. The authors comment that negative results are interesting but do not solve the curability of syphilis. They further suggest that such "negative results must be controlled by a
Failure of Perchlorate to Inhibit Tc-99m Isonitrile Binding by the Thyroid during Myocardial Perfusion Studies
Authors: Bernardo Blum
Journal: Clinical Nuclear Medicine (1992)

The thyroid gland receives an average radiation dose of 3 rads during two Tc-99m isonitrile (MIBI) myocardial perfusion studies, if 20 mCi is administered both at rest and at peak exercise. In patients with coronary artery disease, multiple myocardial perfusion studies may be required, resulting in a high level of thyroid radiation. We attempted to reduce this radiation exposure by blocking thyroidal Tc-99m MIBI uptake with oral potassium perchlorate (KCIO4). Fourteen normal subjects received 0.6g to 0.8g KCIO4 20-25 minutes before tracer injection. Subjects who received KCIO4 at rest (n = 11) did not receive KCIO4 at their stress study, and vice versa (n = 3). Thyroid uptake values were obtained with a thyroid probe 20 minutes after injection for both rest and stress studies and were corrected for saturation effects. There was no difference between fractional thyroid uptake values with and without preceding perchlorate administration: 1.9 +/- 0.5% and 1.8 +/- 0.3% (mean +/- SD), respectively. Failure to block Tc-99m MIBI uptake after intravenous (IV) injection is probably due to high thyroidal blood flow and nonspecific tracer accumulation. The concentration of this radioisotope in adjacent muscles also contributes to the high thyroid radiation dose. In summary, administration of KCIO4 before Tc-99m MIBI studies does not reduce the thyroidal radiation dose or uptake of this tracer, suggesting that thyroidal uptake of this tracer is not mediated by the iodine trapping mechanism.
Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation
Authors: Paulette L. Wright, Jun Yu, Y.P. Peter Di, Robert J. Homer, Geoffrey Chupp, Jack A. Elias, Lauren Cohn, William C. Sessa
Journal: The Journal of Experimental Medicine (2010)

Nogo-B is a member of the reticulon family of proteins (RTN-4B) that is highly expressed in lung tissue; however, its function remains unknown. We show that mice with Th2-driven lung inflammation results in a loss of Nogo expression in airway epithelium and smooth muscle compared with nonallergic mice, a finding which is replicated in severe human asthma. Mice lacking Nogo-A/B (Nogo-KO) display an exaggerated asthma-like phenotype, and epithelial reconstitution of Nogo-B in transgenic mice blunts Th2-mediated lung inflammation. Microarray analysis of lungs from Nogo-KO mice reveals a marked reduction in palate lung and nasal clone (PLUNC) gene expression, and the levels of PLUNC are enhanced in epithelial Nogo-B transgenic mice. Finally, transgenic expression of PLUNC into Nogo-KO mice rescues the enhanced asthmatic-like responsiveness in these KO mice. These data identify Nogo-B as a novel protective gene expressed in lung epithelia, and its expression regulates the levels of the antibacterial antiinflammatory protein PLUNC.
Abstract 801: Clinical application of genomic signature including <i>ALK</i> mutation to the new tumor risk classification for neuroblastoma
Authors: Miki Ohira (-Ichikawa), Toshio Kojima, Takafumi Niwa, Shigeyuki Oba, Shin Ishii, Junko Takita, Motohiro Kato, Seishi Ogawa, Yohko Nakamura, Takehiko Kamijo, Akira Nakagawara
Journal: Cancer Research (2010)

Abstract Neuroblastoma (NBL) is one of the most common pediatric tumor arising from developing sympathetic nervous system. Its clinical and biological behavior is markedly heterogenous ranging from aggressive progression despite of intensive therapy to spontanous regression. NBL DNA shows complex patterns of genomic aberrations including MYCN amplification, deletion of chromosome 1p or 11q, and gain of chromosome 17q. We previously constructed the genomic subgrouping system of NBL based on the array CGH analysis for new tumor risk classification of NBL (Tomioka et al, Oncogene 2008). Analysis of 234 tumors by using 2,464 clones-BAC arrays demonstrated there exist three genomic groups (GG) of chromosomal aberrations in NBL: silent (S), partial gains and/or losses (P) and whole gains and/or losses (W). Each GG was further segregated into subgroups with different clinical outcomes clearly defined by MYCN amplification (MYCN-amp), 1p loss, 11q loss and 17q gain. Importantly, high-resolution array CGH analysis also led us to identify a novel genomic alteration in NBL, the activating mutation and amplification of anaplastic lymphoma kinase (ALK) oncogene on chromosome 2p23. In this study, to conduct the clinical validation of our GG risk classification system, array CGH and mutation analysis of ALK gene of 343 sporadic NBLs (stage 1: 48; stage2: 29; stage 4s: 27; stage 3: 60; stage 4: 179; median follow-up period is 78 months) were performed and the clinical impact of the genomic signatures was assessed. The results were fairly reproducible with our previous data, showing that GG-S or GG-W without MYCN-amp exhibited good prognosis (Ss and Ws, 8-year survival rates: &amp;gt;80%), while GG-P or GG-S accompanying MYCN-amp were very poor (Pa and Sa, 8-year survival rates: &amp;lt;35%). ALK gene abnormalities including mutations and amplification were found in 21 tumors in our dataset (6.1%), which caused fatal outcomes of the patients (p&amp;lt;0.01) especially those with MYCN-amp (ALKmut-/MYCNamp+, n=73 vs. ALKmut+/MYCNamp+, n=10, p=0.16). Interestingly, ALK abnormalities were frequently found in the certain genomic subgroups of the tumors, namely, GG-Pa with 1p loss, GG-Ps with 11q loss and GG-Ws with no partial 1p and 11q losses. These results suggested that the combination of genomic signatures with ALK abnormalities will further improve the potential of our tumor risk classification system of NBL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 801.
Planar Microdevices for Enhanced In Vivo Retention and Oral Bioavailability of Poorly Permeable Drugs
Authors: Hariharasudhan D. Chirra, Ling Shao, Natalie Ciaccio, Cade B. Fox, Jennifer M. Wade, Averil Ma, Tejal A. Desai
Journal: Advanced Healthcare Materials (2014)

The development of novel oral drug delivery platforms for administering therapeutics in a safe and effective manner through the harsh gastrointestinal environment is of great importance. Here, the use of engineered thin planar poly(methyl methacrylate) (PMMA) microdevices is tested to enhance oral bioavailability of acyclovir, a poorly permeable drug. Acyclovir is loaded into the unidirectional drug releasing microdevice reservoirs using a drug entrapping photocross‐linkable hydrogel matrix. An increase in acyclovir permeation across in vitro caco‐2 monolayer is seen in the presence of microdevices as compared with acyclovir‐entrapped hydrogels or free acyclovir solution. Cell proliferation studies show that microdevices are relatively nontoxic in nature for use in in vivo studies. Enhanced in vivo retention of microdevices is observed as their thin side walls experience minimal peristaltic shear stress as compared with spherical microparticles. Unidirectional acyclovir release and enhanced retention of microdevices achieve a 4.5‐fold increase in bioavailability in vivo as compared with an oral gavage of acyclovir solution with the same drug mass. The enhanced oral bioavailability results suggest that thin, planar, bioadhesive, and unidirectional drug releasing microdevices will significantly improve the systemic and localized delivery of a broad range of oral therapeutics in the near future.
Five years of heartsink patients in general practice.
Authors: T. C. O'Dowd
Journal: BMJ (1988)

"Heartsink" patients exasperate, defeat, and overwhelm their doctors by their behaviour. A group of such patients was followed up over five years in a general practice, and this paper describes what happened to them. As a group they were often in employment and in stable relationships, though women were over represented. Half the group were subjected to a management plan which seemed to make them less heartsink over the five year period. While heartsink patients often have serious medical problems, they are a disparate group of individuals whose only common thread seems to be the distress they cause their doctor and the practice. Heartsink as a phenomenon has features that are unique to general practice.
Xenon Ventilation-Perfusion Lung Scans
Authors: Gerald L. Schall
Journal: JAMA (1978)

The use of xenon Xe 133 ventilation-perfusion lung scans for the early diagnosis of inhalation injury was evaluated in 67 patients with acute thermal burns. Study results were interpreted as normal if there was complete pulmonary clearance of the radioactive gas by 150 seconds. Thirty-two scans were normal, 32 abnormal, and three technically inadequate. There were three true false-positive study results and one false-negative study result. Good correlation was found between the scan results and various historical, physical, and laboratory values currently used to evaluate inhalation injury. The scans appeared to be the most sensitive method for the detection of early involvement, often being abnormal several days before the chest roentgenogram. Xenon lung scanning is a safe, easy, accurate, and sensitive method for the early diagnosis of inhalation injury and has important therapeutic and prognostic implications as well. (<i>JAMA</i>240:2441-2445, 1978)
Cardiopulmonary Exercise Testing Before and After Lung and Heart–Lung Transplantation
Authors: MARTIN SCHWAIBLMAIR, HERMANN REICHENSPURNER, CHRISTIAN MÜLLER, JOSEF BRIEGEL, HEINER FÜRST, JÜRGEN GROH, BRUNO REICHART, CLAUS VOGELMEIER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Heart–lung (HLT) and lung transplantation (LT) have been shown to be effective procedures for patients with end-stage cardiopulmonary disorders. As yet, few data exist on the exercise performance of patients before and after thoracic transplantation except with regard to 6-min walk tests. In this article we report cardiopulmonary exercise test results of lung and heart–lung transplant recipients in comparison with their pretransplant values. We studied 103 consecutive recipients of single-lung (n = 46), bilateral lung (n = 32), and heart–lung (n = 25) transplants. Cardiopulmonary exercise testing with a cycle ergometer was performed before and shortly after surgery. Before transplantation, all patients showed severe exercise intolerance and markedly impaired parameters reflecting cardiopulmonary function (e.g., work capacity: 20 ± 11% predicted; oxygen uptake: 34 ± 12% predicted; oxygen pulse: 50 ± 18% predicted; functional dead space ventilation: 57 ± 10% of minute ventilation; alveolar–arterial oxygen difference during exercise: 79 ± 15 mm Hg). At 55 ± 9 d after transplantation, transplant recipients reached maximum oxygen uptakes in the range of 22 to 71% of predicted values; the peak oxygen uptake was increased after transplantation (13.1 ± 3.4 ml/min/kg versus 10.4 ± 3.8 ml/min/kg; p < 0.001). Work capacity, oxygen pulse, tidal volume, and peak minute ventilation did not differ in patients following single- or double-lung tranplantation or HLT. Ventilatory factors did not appear to limit exercise capacity in any group. Despite the persistent limitations in aerobic capacity and work rate seen in many of the recipients, cardiopulmonary performance is reasonably well restored shortly after LT and HLT.
Effectiveness of Combination Therapy With Statin and Another Lipid-Modifying Agent Compared With Intensified Statin Monotherapy
Authors: Kimberly A. Gudzune, Anne K. Monroe, Ritu Sharma, Padmini D. Ranasinghe, Yohalakshmi Chelladurai, Karen A. Robinson
Journal: Annals of Internal Medicine (2014)

Some patients do not tolerate or respond to high-intensity statin monotherapy. Lower-intensity statin combined with nonstatin medication may be an alternative, but the benefits and risks compared with those of higher-intensity statin monotherapy are unclear.To compare the clinical benefits, adherence, and harms of lower-intensity statin combination therapy with those of higher-intensity statin monotherapy among adults at high risk for atherosclerotic cardiovascular disease (ASCVD).MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to July 2013, with an updated MEDLINE search through November 2013.Randomized, controlled trials published in English.Two reviewers extracted information on study design, population characteristics, interventions, and outcomes (deaths, ASCVD events, low-density lipoprotein [LDL] cholesterol level, adherence, and adverse events). Two independent reviewers assessed risk of bias.A total of 36 trials were included. Low-intensity statin plus bile acid sequestrant decreased LDL cholesterol level 0% to 14% more than mid-intensity monotherapy among high-risk hyperlipidemic patients. Mid-intensity statin plus ezetimibe decreased LDL cholesterol level 5% to 15% and 3% to 21% more than high-intensity monotherapy among patients with ASCVD and diabetes mellitus, respectively. Evidence was insufficient to evaluate LDL cholesterol for fibrates, niacin, and ω-3 fatty acids. Evidence was insufficient for long-term clinical outcomes, adherence, and harms for all regimens.Many trials had short durations and high attrition rates, lacked blinding, and did not assess long-term clinical benefits or harms.Clinicians could consider using lower-intensity statin combined with bile acid sequestrant or ezetimibe among high-risk patients intolerant of or unresponsive to statins; however, this strategy should be used with caution given the lack of evidence on long-term clinical benefits and harms.Agency for Healthcare Research and Quality.
Development of an Os Calcaneal Spur in a Boy Between the Ages of 10 and 14 Years
Authors: B. Reeves
Journal: Annals of the Rheumatic Diseases (1965)

Calcaneal spurs are seen frequently in adults with rheumatoid disease, ankylosing spondylitis, and Reiter's syndrome; the differences between the mature spurs have been well described by Mason, Murray, Oates, and Young (1959).The process of development of these spurs does not, however, appear to have been recorded.It was therefore thought that this series of x rays taken over a 4-year period starting at the age of 10 years would be of interest.
The Oldest Old
Authors: Edward W. Campion
Journal: New England Journal of Medicine (1994)

In the United States, as well as in other developed countries, the elderly population is getting older. From 1960 to 1990, the number of Americans 85 years of age or older increased by 232 percent, whereas the number 65 years of age or older increased by 89 percent and the total population grew by just 39 percent1. Currently, 3.5 million U.S. citizens are 85 or older2. In this age group, known as the oldest old, women outnumber men by 2.6 to 1. At the age of 85, life expectancy is 6.4 years for white women and 5.2 years . . .
Sulphasalazine in rheumatoid arthritis: desensitising the patient with a skin rash.
Authors: D E Bax, R S Amos
Journal: Annals of the Rheumatic Diseases (1986)

Sulphasalazine has been shown to be useful in the management of rheumatoid arthritis. However, its use may be complicated by a skin rash. Eight patients with a rash have undergone desensitisation, the aim of which was to achieve a daily dose of 2 g sulphasalazine. This was successful in five patients, partially successful in two, and failed in one patient. Desensitisation to sulphasalazine is a simple outpatient procedure, which subsequently allows the majority of patients developing a skin rash to continue treatment.
Functional Disorders of the Urinary Bladder
Authors: Herbert S. Talbot
Journal: New England Journal of Medicine (1958)

OF the functions man shares with lower animals, few have been so modified as micturition to meet the peculiar demands of human life. It is not true, as some have stated, that the urinary bladder is a convenience rather than a necessity. A person may live without one, as, indeed, he may live without sight, hearing, one or more of his extremities or sundry other organs or parts thereof. Yet it is difficult to conceive of the survival of a species whose members left trails of urine wherever they passed. For civilized man, however, it will not do simply to . . .
If it doesn't work, stop it
Authors: Ludovic Reveiz
Journal: BMJ (2004)

Editor—Assessing effectiveness and benefit in epidemiological studies entails several degrees of imprecision and uncertainty at the individual level while its estimator is defined for a population. A single disease entity may have varied manifestations in different patients and divergent outcomes.1​1




Figure 1




As Anderson and Groves emphasise,2 Archie Cochrane posed three key questions to ask about a healthcare intervention: “Can it work?” “Does it work in practice?” and “Is it worth it?” We usually use rules to decide between “yes,” “not sure,” and “no.” By doing this we assume Aristotelian logic and the classic current definition that “health and disease are opposites and that they are dual and contradictory attributes.”1

Why do doctors use treatments that do not work?3 People usually do not require precise numerical information, and yet they are capable of making decisions. They accept noisy and imprecise input4; so do doctors.

Having a huge number of input variables (patient background, expectations, behaviour, and beliefs, disease manifestations, laboratory results, etc), doctors use “fuzzy logic” algorithms (grade of evidence, personal knowledge, cost, ritual, mystique, etc) to decide treatments. Evidence is one of the most important pieces of the complex system, but not the only one. Fuzzy logic has been developed to deal with the concept of partial truth values between completely true and completely false. It mimics human control logic and may be applied to improve knowledge in epidemiological and medical problems.1,4
Pharmacogenetic Interactions Between β-Blocker Therapy and the Angiotensin-Converting Enzyme Deletion Polymorphism in Patients With Congestive Heart Failure
Authors: Dennis M. McNamara, Richard Holubkov, Karen Janosko, Amy Palmer, Jue J. Wang, Guy A. MacGowan, Srinivas Murali, Warren D. Rosenblum, Barry London, Arthur M. Feldman
Journal: Circulation (2001)

Background —Activation of the renin-angiotensin and sympathetic nervous systems adversely affect heart failure progression. The ACE deletion allele ( ACE D ) is associated with increased renin-angiotensin activation; however, its influence on patient outcomes remains uncertain, and the pharmacogenetic interactions with β-blocker therapy have not been previously evaluated. Methods and Results —We prospectively followed 328 patients (age, 56.1±11.9 years) with systolic dysfunction (left ventricular ejection fraction, 0.24±0.08) to assess the impact of the ACE D allele on transplant-free survival (median follow-up, 21 months). Transplant-free survival was compared by genotype for the whole cohort and separately in patients with (n=120) and those without β-blocker therapy (n=208) at the time of entry. Transplant-free survival was significantly poorer for patients with the D allele (1-year percent survival II/ID/DD =94/77/75; 2-year=78/65/60; ordered log-rank test, P =0.044). In patients not treated with β-blockers, the adverse impact of ACE D allele was dramatically increased (1-year percent survival II/ID/DD =95/75/67; 2-year=81/61/48; P =0.005). In contrast, in patients receiving β-blocker therapy, no influence of ACE genotype on transplant-free survival was evident (1-year percent survival II/ID/DD =91/80/86; 2-year=70/71/77; P =0.73). Conclusions —In a cohort of patients with systolic dysfunction, the ACE D allele was associated with a significantly poorer transplant-free survival. This effect was primarily evident in patients not treated with β-blockers and was not seen in patients receiving therapy. These findings suggest a potential pharmacogenetic interaction between the ACE D/I polymorphism and therapy with β-blockers in the determination of heart failure survival.
THE PHYSICIAN AS A SOCIAL ECONOMIC FACTOR.
Authors: EDGAR J. SPRATLING
Journal: JAMA (1902)

In the long-forgotten ages, while men yet lived in caves, the figure that stood out in boldest relief was the medicine man. When society began slowly and timidly to organize itself into a body politic, the chipped flint doing duty as both tool and weapon, the grain about which it crystallized was the ever present medicine-man-priest. To him came his tribe, singly and collectively, asking enlightenment and guidance. His war chief, however brave, however fierce, was only tribal warrior leader, he himself being the real ruler, holding the scepter of life and death over his people. His remedies were few and therapeutically worthless, but his dogmas were all powerful. This picture is faithfully reflected among all primitive peoples even unto this day. As culture made progress slowly, very slowly at first, but gaining rapidity with the passing of the centuries, the priest-physician was found ever in the forefront, grasping every
MARRIAGE AND HEREDITARINESS OF EPILEPTICS
Authors: M. G. Echeverria
Journal: American Journal of Psychiatry (1880)

The following Errata should be inserted in the number for October, 1880, with Dr. Echeverria's article on Marriage of Epileptics. Page 206. From 68 patients with hereditary predisposition. No. of patients. No. of children. Total. 14 (12 families) 1 12 10 (8 families) 2 16 15 (14 families) 3 42 The third line of the paragraph following the table should read . . . . . who, in the latter case, also have had. Page 184. In second paragraph eighth line should be—but could be dissolved.