tbuckley/cabot-search huggingface dataset:
Complete Deficiency of Leukocyte Glucose-6-Phosphate Dehydrogenase with Defective Bactericidal Activity
Authors: M. Robert Cooper, Lawrence R. DeChatelet, Charles E. McCall, Mariano F. La Via, Charles L. Spurr, Robert L. Baehner
Journal: Journal of Clinical Investigation (1972)

A 52 yr old Caucasian female (F. E.) had hemolytic anemia, a leukemoid reaction, and fatal sepsis due to Escherichia coli. Her leukocytes ingested bacteria normally but did not kill catalase positive Staphylococcus aureus, Escherichia coli, and Serratia marcescens. An H(2)O(2)-producing bacterium, Streptococcus faecalis, was killed normally. Granule myeloperoxidase, acid and alkaline phosphatase, and beta glucuronidase activities were normal, and these enzymes shifted normally to the phagocyte vacuole (light and electron microscopy). Intravacuolar reduction of nitroblue tetrazolium did not occur. Moreover, only minimal quantities of H(2)O(2) were generated, and the hexose monophosphate shunt (HMPS) was not stimulated during phagocytosis. These observations suggested the diagnosis of chronic granulomatous disease. However, in contrast to control and chronic granulomatous disease leukocytes, glucose-6-phosphate dehydrogenase activity was completely absent in F. E. leukocytes whereas NADH oxidase and NADPH oxidase activities were both normal. Unlike chronic granulomatous disease, methylene blue did not stimulate the hexose monophosphate shunt in F. E. cells. Thus, F. E. and chronic granulomatous disease leukocytes appear to share certain metabolic and bactericidal defects, but the metabolic basis of the abnormality differs. Chronic granulomatous disease cells lack oxidase activity which produces H(2)O(2); F. E. cells had normal levels of oxidase activity but failed to produce NADPH due to complete glucose-6-phosphate dehydrogenase deficiency. These data indicate that a complete absence of leukocyte glucose-6-phosphate dehydrogenase with defective hexose monophosphate shunt activity is associated with low H(2)O(2) production and inadequate bactericidal activity, and further suggest an important role for NADPH in the production of H(2)O(2) in human granulocytes.
CORONARY ARTERY CALCIUM SCORE VERSUS A MULTIPLE BIOMARKER APPROACH FOR CORONARY HEART DISEASE RISK ASSESSMENT: MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
Authors: Jamal S. Rana, Michael Pencina, Michael Blaha, Roger Blumenthal, Arthur Agatston, James K. Min, Ron Blankstein, Nathan D. Wong, Joao Lima, Leslee J. Shaw, Mathew J. Budoff, Mary Cushman, Daniel Berman, Khurram Nasir
Journal: Journal of the American College of Cardiology (2013)
Combined Analysis of Two Multicenter, Randomized, Placebo-Controlled Studies of Pamidronate Disodium for the Palliation of Bone Pain in Men With Metastatic Prostate Cancer
Authors: Eric J. Small, Matthew R. Smith, John J. Seaman, Stephanie Petrone, Mildred Ortu Kowalski
Journal: Journal of Clinical Oncology (2003)

Bone metastases occur in approximately 80% of patients with advanced prostate cancer. Pain is common in these patients. The purpose of this study was to evaluate the effect of an intravenous bisphosphonate, pamidronate disodium, on pain control in metastatic prostate cancer patients.Two multicenter, double-blind, randomized, placebo-controlled trials were conducted in patients with bone pain due to metastatic prostate cancer, with disease progression after first-line hormonal therapy. Intravenous pamidronate disodium (90 mg) or placebo was administered every 3 weeks for 27 weeks. Efficacy was measured via self-reported pain score (Brief Pain Inventory), analgesic use, the proportion of patients with a skeletal-related event (SRE; defined as pathologic fracture, radiation or surgery to bone, spinal cord compression, or hypercalcemia), and a pilot quantitative measurement of mobility. Laboratory evaluations included serum prostate-specific antigen, interleukin-6, bone alkaline phosphatase, and urinary bone resorption markers.Results of the two trials were pooled. There were no sustained significant differences between the pamidronate and placebo groups in self-reported pain measurements, analgesic use, proportion of patients with an SRE, or mobility at week 9 or 27. Urinary bone resorption markers were suppressed in the pamidronate group compared with placebo.Pamidronate disodium failed to demonstrate a significant overall treatment benefit compared with placebo in palliation of bone pain or reduction of SREs. Evaluation of more potent bisphosphonates in patients with prostate cancer is warranted.
Concentrations of nitrogen mustard in the air during topical treatment of patients with mycosis fungoides
Authors: W.A. VLOTEN, A.C.M. COOIJMANS, J. POEL, J. MEULENBELT
Journal: British Journal of Dermatology (1993)

Acute and chronic side-effects have been reported during topical treatment of mycosis fungoides with nitrogen mustard (HN2). In order to estimate the risk for the nurse applying topical HN2, the concentration of HN2 in the air during treatment was measured. Air samples were obtained before, and during the 20-min treatment period close to the nurse and patient, and continuously at a distance of 1 m from the patient. The mean concentration of HN2 in the air during treatment was 0.036 mg/m3. Immediately after treatment the concentration dropped to 0.004 mg/m3. The mean cumulative concentration in the room during the 3 1/2 h of the experiment was 0.012 mg/m3. If the MAC (maximal allowable concentration) value of 0.05 mg/m3 for the comparable sulphur mustard is used as a guideline, then with a treatment procedure of 20 min this level is not exceeded. Nevertheless, it is important to minimize the exposure of nursing staff to HN2.
Liquid Biopsies: Genotyping Circulating Tumor DNA
Authors: Luis A. Diaz, Alberto Bardelli
Journal: Journal of Clinical Oncology (2014)

Genotyping tumor tissue in search of somatic genetic alterations for actionable information has become routine practice in clinical oncology. Although these sequence alterations are highly informative, sampling tumor tissue has significant inherent limitations; tumor tissue is a single snapshot in time, is subject to selection bias resulting from tumor heterogeneity, and can be difficult to obtain. Cell-free fragments of DNA are shed into the bloodstream by cells undergoing apoptosis or necrosis, and the load of circulating cell-free DNA (cfDNA) correlates with tumor staging and prognosis. Moreover, recent advances in the sensitivity and accuracy of DNA analysis have allowed for genotyping of cfDNA for somatic genomic alterations found in tumors. The ability to detect and quantify tumor mutations has proven effective in tracking tumor dynamics in real time as well as serving as a liquid biopsy that can be used for a variety of clinical and investigational applications not previously possible.
INTRADURAL TUMOR OF THE SPINAL CORD WITH OPERATION
Authors: EDWARD E. MAYER
Journal: JAMA (1910)

REPORT OF CASE AND ANALYSIS BY DR. MAYER  The diagnosis of tumors of the spinal cord is no longer difficult, nor is their operability in a majority of cases a debatable question. Indeed the large number of patients successfully operated on has fully justified the optimism of Victor Horsley as expressed by him three decades ago.  Since then in every country many have contributed to our knowledge of tumors of the spinal cord—the recent books of Malaise, Bruns, Oppenheim and Schlesinger covering well the entire subject—so that we shall try to avoid being too discursive.  CASE REPORT  Clinical
HYPERSENSITIVENESS TO SOLUBLE SPECIFIC SUBSTANCES FROM YEAST-LIKE FUNGI
Authors: E. Mott, H. D. Kesten
Journal: The Journal of Experimental Medicine (1931)

The anterior chamber of the rabbit eye was sensitized by the local injection of heat-killed Monilia psilosis. Subsequent intravenous injection of a polysaccharide fraction prepared from the same organism elicited a reaction in the sensitized eye in five of twelve rabbits.
Transport of Propranolol and Lidocaine through the Rat Blood-Brain Barrier. PRIMARY ROLE OF GLOBULIN-BOUND DRUG
Authors: William M. Pardridge, Roland Sakiyama, Gary Fierer
Journal: Journal of Clinical Investigation (1983)

Basic lipophilic drugs such as propranolol and lidocaine are strongly bound by alpha(1)-acid glycoprotein, also called orosomucoid. Although the liver is known to rapidly clear plasma protein-bound propranolol or lidocaine, it is generally regarded that peripheral tissues, such as brain or heart, are only exposed to the small fraction of drug that is free or dialyzable in vitro. The "free drug" hypothesis is subjected to direct empiric testing in the present studies using human sera and an in vivo rat brain paradigm. Serum from 27 human subjects (normal individuals, newborns, or patients with either metastatic cancer or rheumatoid arthritis) were found to have up to a sevenfold variation in orosomucoid concentrations. The free propranolol or lidocaine as determined in vitro by equilibrium dialysis at 37 degrees C varied inversely with the orosomucoid concentration. Similarly the rate of transport of propranolol or lidocaine through the blood-brain barrier (BBB) was inversely related to the existing serum concentration of orosomucoid. However, the inhibition of rat brain extraction of drug by orosomucoid in vivo was only about one-fifth of that predicted by free drug measurements in vitro. This large discrepancy suggested orosomucoid-bound drug was readily available for transport into brain in vivo. Studies using purified human orosomucoid in the rat brain extraction assay also showed that orosomucoidbound propranolol or lidocaine is readily transported through the BBB. Conversely, albumin-bound propranolol or lidocaine was not transported through the BBB. The studies using albumin provide evidence that the in vivo rat brain paradigm used in the present investigations is capable of confirming, when possible, predictions made by the "free drug" hypothesis. These data suggest that the amount of circulating propranolol or lidocaine that is available for transport into a peripheral tissue such as brain is not restricted to the free (dialyzable) moiety but includes the much larger globulin-bound fraction. Therefore, existing pharmacokinetic models should be expanded to account for the transport of protein-bound drugs into peripheral tissues similar to what is known to occur in liver.
Kant, Sartre, and the Categorical Imperative
Authors: Nicholas R. Rorick
Journal: JAMA (1982)

<h3>To the Editor.—</h3> With regard to the editorial "Acronyms and Initialisms" by James Ransom, PhD (1981; 246:1941), I agree with most of what he says, but was it not Kant, rather than Sartre, who first enunciated the principle that "Each of us should make decisions about conduct as if our every act were irretrievably binding on mankind"? My Jesuit mentors at the University of Santa Clara called that Kant's "categorical imperative."
Earlier diagnosis is needed to reduce deaths and disability from aneurysmal subarachnoid haemorrhage
Authors: S. Mayor
Journal: BMJ (2013)

Failure by GPs and hospital doctors to recognise symptoms of aneurysmal subarachnoid haemorrhage contributes to longer time to treatment and poorer outcomes in England, Wales, and Northern Ireland than in other developed countries, show results from an audit.1

The latest report of the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) recommends introducing standard protocols of care to improve the diagnosis and stabilisation of patients with subarachnoid haemorrhage, referral to neurosurgical centres, and subsequent rehabilitation. It also advises setting up formal networks of care, linking all secondary care hospitals to designated regional neurosurgical and neuroscience centres.

“This potentially fatal disease has to progress from the GP’s surgery or accident and emergency, where it may present ostensibly as a simple headache, to the operative setting as fast as possible,” said Bertie Leigh, NCEPOD’s chairman. …
Patchy eosinophil distributions in an esophagectomy specimen from a patient with eosinophilic esophagitis: Implications for endoscopic biopsy
Authors: Hedieh Saffari, Kathryn A. Peterson, John C. Fang, Carolin Teman, Gerald J. Gleich, Leonard F. Pease
Journal: Journal of Allergy and Clinical Immunology (2012)
Book Review My Mother's Hip: Lessons from the World of Eldercare By Luisa Margolies. 339 pp. Philadelphia, Temple University Press, 2004. $66.50 (cloth); $22.95 (paper). 1-59213-237-5 (cloth); 1-59213-238-3 (paper).
Authors: Helen Hoenig
Journal: New England Journal of Medicine (2005)
Genetic engineering reverses antibiotic resistance
Authors: K. Abbasi
Journal: BMJ (1997)

Researchers have developed a genetic engineering technique that for the first time allows drug resistant bacteria to be rendered drug sensitive. This may prove to be a cheaper method of negating antibiotic resistance than the current approach of developing new drugs.

A team of biologists from Yale University in the United States, led by Nobel prize winner Professor Sidney Altman, has used plasmids that contain synthetic genes coding for small oligoribonucleotides, called external guide sequences (EGSs), to infiltrate drug resistant strains of Escherichia coli ( Proceedings of the National …
Plasma cell balanitis treated with tacrolimus 0.1%
Authors: G.A. Moreno-Arias, A. Camps-Fresneda, C. Llaberia, J. Palou-Almerich
Journal: British Journal of Dermatology (2005)

Background Plasma cell balanitis or balanitis of Zoon (BZ) is a frequent diagnosis in mature men and lesions are generally localized on the glans but may involve the prepuce; its aetiology remains unknown. Objectives To present our experience with tacrolimus 0·1% ointment in the treatment of two patients with BZ refractive to other topical treatments. Patients and methods Two uncircumcised mature caucasian males were seen, both presenting with BZ; topical tacrolimus 0·1% ointment twice daily was prescribed in each case. Results Marked improvement of the lesions in both patients has been observed, with follow-up of 1 year and 10 months, respectively. Conclusions Topical tacrolimus 0·1% ointment is an effective and safe treatment for BZ.
Apical membrane chloride/base exchange in the rat proximal convoluted tubule.
Authors: R J Alpern
Journal: Journal of Clinical Investigation (1987)

To examine whether Cl/base exchange is present on the apical membrane of the proximal convoluted tubule, cell pH was measured fluorometrically in the in vivo microperfused rat proximal tubule with (2',7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein. The effect of luminal chloride addition was examined in tubules perfused symmetrically with chloride-free solutions. In the absence of inhibitors, luminal chloride addition did not affect cell pH. However, after inhibition of basolateral membrane anion transport with peritubular 4-acetamido-4'-isothiocyano-(2,2')-disulfonic-stilbene (to amplify effects of apical membrane transport on cell pH), luminal chloride addition caused a small cell acidification (delta pHi = 0.02). When 1 mM formate was added to the solutions, luminal chloride addition caused a larger change in cell pH (delta pHi = 0.06) that was inhibited by (4,4')-diisothiocyano-(2,2')-disulfonic-stilbene. This stimulation of Cl/base exchange was not seen with 1 mM acetate addition. These results demonstrate apical membrane Cl/base exchange, a significant fraction of which is dependent on the presence of formate and probably represents Cl/formate exchange.
False-Positive Tests for 5-Hydroxyindole-acetic Acid
Authors: Olli Mustala
Journal: JAMA (1970)

<h3>To the Editor.—</h3> The article "False-Positive Tests for Urinary 5-Hydroxyindole-acetic Acid: Error in Laboratory Determination Caused by Glyceryl Guaiacolate" by Pedersen et al (<b>211</b>:1184, 1970) is an example of how inadequate use of the medical literature leads to unnecessary duplication and waste of scientific effort. Eight years ago Pitkänen et al<sup>1</sup>described a patient who was operated on for a carcinoid syndrome because of a falsely elevated test for 5-hydroxyindole-acetic acid (5HIAA) caused by the ingestion of glyceryl guaiacolate. This inaccurate result was obtained using the method of Udenfriend et al.<sup>2</sup>Indeed, it was known even prior to this case report that a metabolite of glyceryl guaiacolate yielded a colored product in the nitrosonaphthol reaction if pretreatment was not included.<sup>3</sup>In the article by Pitkänen et al all the facts were detailed which are now eight years later presented by Pedersen et al. The nature and
Portal vein embolization with steel coils and absolute ethanol: A comparative experimental study with canine liver
Authors: Koichiro Yamakado, Kan Takeda, Yoshiya Nishide, Jugangu Jin, Kaname Matsumura, Atsuhiro Nakatsuka, Tadanori Hirano, Noriyuki Kato, Tsuyoshi Nakagawa
Journal: Hepatology (1995)

Portal vein embolization (PVE) is expected to have an adjuvant effect on the treatment of human liver tumors with transcatheter hepatic arterial embolization (TAE). In this experimental study, PVE was tried using two kinds of embolic materials, steel coils (coils) and absolute ethanol (ethanol). The aim of this article is to compare the effectiveness between the two methods. Five dogs and 12 dogs were treated with coils and ethanol, respectively. The second order portal branches were embolized. Embolization effects of each embolic material on the hepatic vessels and the liver parenchyma were studied angiographically and histologically. PVE with coils achieved immediate occlusion of the embolized vessels in all dogs. Unexpectedly, unembolized vessels were also constricted and/or obstructed in 4 of 5 dogs during a 4-week follow-up period. Histological examination showed no hepatic necrosis in all dogs. By contrast, in the dogs treated with ethanol, venous occlusion was achieved immediately after embolization with ethanol of 0.4 mL/kg or more. The embolized vessels remained occluded and no obstruction of unembolized vessels was observed until 4 weeks after embolization. Hepatic necrosis was observed in the segments where portal veins were occluded. The degree of parenchymal damage was proportional to the injected ethanol dose. Judging from these results, ethanol is likely to be more suitable than coils as an embolic material for PVE. PVE with coils is often dangerous because unembolized vessels might be occluded unexpectedly. For the clinical use of PVE with ethanol, the appropriate dose of injection should be investigated.
Tiling-resolution array-CGH reveals the pattern of DNA copy number alterations in acute lymphoblastic leukemia with 21q amplification: the result of telomere dysfunction and breakage/fusion/breakage cycles?
Authors: E Kuchinskaya, A Nordgren, M Heyman, J Schoumans, M Corcoran, J Staaf, Å Borg, S Söderhäll, D Grandér, M Nordenskjöld, E Blennow
Journal: Leukemia (2007)
Physical indicators of emotional abuse in children.
Authors: M Ewart
Journal: BMJ (1980)

that should be pursued between teacher, child, and parents.There is evidence that the pendulum phenomenon is now heralding an era of "narrow punitive education associated with the bullying of children and adolescents,"'3 and that this would be welcome in some quarters.Let us hope that sufficient people feel strongly enough to ensure that the next decade does not provide further inspiration for the Pink Floyd.
Research samples are hard to obtain these days
Authors: S. A Khan
Journal: BMJ (2002)

I was a clinical research fellow coming to the end of my three year research programme on the aetiology of hepatobiliary cancers. One of my final studies was to analyse bile, collected via endoscopic retrograde cholangiopancreatography, with magnetic resonance spectroscopy to look for differences between patients with cancer and those without.

The initial spectroscopy readings were promising, with various bizarre, never previously seen peaks proudly announcing themselves. My initial excitement that I was on the verge of discovering the cause of biliary cancer was soon cut short, however, on realising that these peaks were probably due to the contrast agent used during cholangiopancreatography. Time was running out—I had to submit my thesis within a few months …
2005 Presidential Address: Diabetes: Past, Present, and Future
Authors: Alan D. Cherrington
Journal: Diabetes Care (2006)

One of my favorite authors is the English writer Charles Dickens. His novels captured the human spirit, while detailing life in England in the 1800s. In 1843, he published a book entitled “A Christmas Carol.” In it, Ebenezer Scrooge, a stingy man of business is visited by the ghost of his deceased partner, Jacob Marley. The purpose of the visit is to prepare Scrooge for the subsequent appearance of three spirits: the spirit of Christmas past, the spirit of Christmas present, and the spirit of Christmas yet to come. The first spirit provides Scrooge with a look back at his early days. The second spirit opens his eyes to the reality of the present. Finally, the third, and most ominous spirit, allows him a glimpse into his future.

It is my goal today to use this approach to examine the epidemic of diabetes in the U.S. I will first remind you of where we were a generation ago; I will then focus on the situation today, and finally I will attempt to look into the future. The first spirit to visit Scrooge was the ghost of Christmas past, so let us begin there.

In 1985, there were 6.4 million adults with diagnosed diabetes in the U.S. The cost of the disease that year (both direct and indirect) was 14 billion dollars. The National Institutes of Health (NIH) investment in diabetes research was only 189 million dollars. The American Diabetes Association (ADA) and the Juvenile Diabetes Research Foundation (JDRF), on the other hand, were collectively investing only 8.2 million dollars.

By 1990, there were 6.7 million adults with diagnosed diabetes, but only four states had a prevalence >6%. Treatment options were limited. Five insulin preparations were available, including the newly approved human insulin. For the treatment of type 2 diabetes, the …
ESSENTIALS IN THE PREVENTION OF TUBERCULOSIS IN INFANCY AND CHILDHOOD
Authors: S. ADOLPHUS KNOPF
Journal: JAMA (1927)

The prevention of tuberculosis in infancy and childhood must begin with preventing the child from being born of tuberculous parents. With all due respect for certain religious teachings, it is the physician's duty to prevent tuberculous progeny. The recent studies of Opie and McPhedran<sup>1</sup>at the Henry Phipps Institute on the spread of tuberculosis within families emphasize the necessity of this precaution. Their investigations showed that massive glandular tuberculosis of the tracheobronchial lymph nodes, recognizable by roentgenologic examination, was found thirty-one times in children in forty-two families in which there was open tuberculosis. Neither man nor woman has a right to marry when actively ill with tuberculosis; but they may marry and have children when the disease apparently has been arrested. Also, persons in whom the disease is inactive may marry provided they postpone their begetting of progeny for at least one year to be sure that relapse will