tbuckley/cabot-search huggingface dataset:
Coagulation system activation and increase of D‐dimer levels in peripheral arterial occlusive disease
Authors: M. De Buyzere, J. Philippé, D. Duprez, G. Baele, D. L. Clement
Journal: American Journal of Hematology (1993)

The aim of the present study was to document coagulation system activation and basal fibrinolysis in peripheral arterial occlusive disease (PAOD) at stage II of Fontaine's classification. In 34 patients, prothrombin fragment (F1 + 2), thrombin-antithrombin III complexes (TAT), and D-dimer concentrations were evaluated before and after a standard treadmill test. Basal levels in PAOD of F1 + 2 (1.25 +/- 0.19 nmol/liter) and of TAT (3.34 +/- 0.35 micrograms/liter) were significantly increased compared to those obtained in age- and sex-matched healthy controls (0.68 +/- 0.06 nmol/liter and 2.30 +/- 0.33 micrograms/liter, respectively), showing baseline activation of the clotting cascade. A secondary activation of the fibrinolytic system was evidenced by the highly significant increase of basal D-dimers (719 +/- 99 ng/dl in PAOD vs. 229 +/- 37 ng/dl in controls). Treadmill exercise failed to increase the study parameters significantly further. Walking distance (583 +/- 40 m) was correlated with the preexercise ankle to brachial systolic blood pressure ratio (r = 0.485, P < 0.005) and inversely with the level of D-dimers (r = -0.425, P < 0.02). Under baseline conditions, the latter parameter was correlated as well with the antigen concentration of urokinase-type plasminogen activator (u-PA; r = 0.503, P < 0.002). These results indicate that stage II PAOD is characterized by an activation of the clotting cascade in baseline conditions evidenced by increased F1 + 2 and TAT. A secondary activation of the fibrinolytic system with increased u-PA antigen levels accounts for the elevated D-dimers. Treadmill exercise was unable to increase these parameters further.
A CASE IN WHICH A LARGE BONE CAVITY WAS HEALED BY MEANS OF THIERSCH GRAFTS.
Authors: JOHN PRENTISS LORD
Journal: JAMA (1902)

Frank Mocha, a farmer aged 60, referred by Dr. Gilmore, was admitted to St. Joseph Hospital, Oct. 21, 1901. The patient had an acute suppurative osteomyelitis of the upper half of the left tibia, which was engrafted upon a chronic inflammation of the same character, which had been of two years' standing. He had the same trouble, in the same place, when six years of age. He was operated on the day after admission, and a very putrid suppurating focus was removed, which included the medulla and cancella of the greatly enlarged upper half of the bone. The erasion extended to the cartilages forming the knee joint. The cavernous portion of the excavation was large and about four cm. deep and three cm. wide. It was filled with pure carbolic acid, which was allowed to remain for about one minute; then the cavity was flushed out and filled with alcohol,
CORONARY ATHEROSCLEROTIC PLAQUE CHANGE OF NON-CULPRIT LESIONS IN HEMODIALYSIS PATIENTS AFTER PERCUTANEOUS CORONARY INTERVENTION
Authors: Kuninobu Kashiyama, Shinjo Sonoda, Yoshitaka Muraoka, Yoshiyuki Suzuki, Yuki Tsuda, Masaru Araki, Masahiro Okazaki, Yutaka Otsuji
Journal: Journal of the American College of Cardiology (2014)
Weight and Risk for Breast Cancer
Authors: Jennifer L. Kelsey, John Baron
Journal: JAMA (1997)

For many years it has been accepted that heavy body weight increases a woman's risk for breast cancer. Since weight is one of the few potentially modifiable risk factors for breast cancer identified to date, understanding the relationship between weight and breast cancer is of considerable importance. However, as Huang et al<sup>1</sup>state in the first sentence of their article in this issue of<i>JAMA</i>, "The relation of body weight to breast cancer is complex." See also p 1407. One of the first complexities to be recognized was that the association between heavy weight and breast cancer applies to postmenopausal women but not to premenopausal women.<sup>2</sup>This finding makes sense if, as is commonly believed, estrogens and possibly progesterone are important in the etiology of breast cancer.<sup>3</sup>Among premenopausal women, most studies have noted that heavy women have a somewhat reduced risk for breast cancer.<sup>4</sup>Recent
Minimization of Heterocyclic Amines and Thermal Inactivation of Escherichia coli in Fried Ground Beef
Authors: C. P. Salmon
Journal: JNCI Journal of the National Cancer Institute (2000)

Heterocyclic amine carcinogens are formed during the cooking of a number of foods, especially well-done meats. Lower temperatures and shorter cooking times can minimize the formation of these carcinogens, yet a major food safety concern is that pathogens in the meat must be thermally inactivated. This study investigated cooking techniques that minimize heterocyclic amine formation while simultaneously destroying contaminating bacteria.Ground beef patties were inoculated with Escherichia coli K12 bacteria and fried to internal temperatures ranging from 35 degrees C to 70 degrees C in a skillet preheated to 160 degrees C, 180 degrees C, or 200 degrees C. Each patty was then analyzed for four common heterocyclic amines and for surviving bacteria. Additionally, the frequency of turning of the beef patty during cooking was varied (a single turn or multiple turns), length of time required for each patty to reach 70 degrees C was recorded, and heterocyclic amine levels were determined. An additional pan temperature of 250 degrees C was tested for its effect on heterocyclic amine formation but not on bacterial killing. Statistical tests were two-sided.Colony-forming bacteria were reduced by five orders of magnitude at internal temperatures greater than 60 degrees C, regardless of cooking method, and were completely inactivated at 70 degrees C. For patties turned just once, heterocyclic amine levels increased as the cooking temperatures increased. However, levels of heterocyclic amines were statistically significantly lower with turning every minute. For each pan temperature, patties reached 70 degrees C internal temperature sooner when they were turned every minute than when they were turned just once during cooking.Lowering the pan temperature and turning the patties frequently can greatly reduce the formation of heterocyclic amines and can simultaneously achieve bacterial inactivation with little or no increase in cooking time, ensuring a product that is safe for human consumption.
Partial Immune Reconstitution in a Patient with the Acquired Immunodeficiency Syndrome
Authors: Lane Hc, Masur H, Longo Dl, Klein Hg, Rook Ah, Quinnan Gv, Steis Rg, Macher A, Whalen G, Edgar Lc
Journal: New England Journal of Medicine (1984)

THE acquired immunodeficiency syndrome (AIDS) is a disease of the immune system that results in the development of life-threatening opportunistic infections or unusual neoplasms or both. Although effective therapies exist for many of the infectious and neoplastic complications of this syndrome, no successful treatment has been developed for the underlying immune defect. Thus, patients are susceptible to recurrent and life-threatening infections and progressive neoplastic processes. The overall mortality in patients with this syndrome remains at approximately 40 per cent. However, since no reversals of the underlying immune dysfunction have reportedly occurred either spontaneously or with therapy, the disease appears to . . .
Defects in DNA and globin messenger RNA in homozygotes for hemoglobin Lepore.
Authors: F Ramirez, J G Mears, U Nudel, A Bank, L Luzzatto, G DiPrisco, R D'Avino, G Pepe, L Camardella, R Gambino, R Cimino, N Quattrin
Journal: Journal of Clinical Investigation (1979)

Globin messenger RNA (mRNA) isolated from three patients homozygous for hemoglobin Lepore is shown to have a marked reduction of the amount of beta-like globin mRNA (Lepore-globin mRNA sequences) compared with alpha-globin mRNA by molecular hybridization. The relative amounts of alpha- and Lepore mRNA are similar to the amounts of alpha- and Lepore globin synthesized in intact cells and by isolated mRNA in a cell-free system. It is also demonstrated that Lepore-globin mRNA can completely hybridize to full-length or nearly full-length beta-globin specific complementary DNA and protect it from nuclease digestion, indicating close homology between the delta-mRNA sequences present in Lepore mRNA and the beta-complementary-DNA probe. We have also quantitated the numbers of beta-like globin gene sequences in genomic Lepore DNA by molecular hybridization and demonstrated a reduction in their number consistent with the Lepore gene being a delta beta-gene fusion product.
Japan loans cash to help curb rising incidence of polio in Pakistan
Authors: S. Arie
Journal: BMJ (2011)

Japan has provided a $65m (£40m; €45m) loan to help efforts to eradicate polio in Pakistan amid concern that rising numbers of cases there could undermine global progress on wiping out the disease.

The number of recorded cases of polio in Pakistan is 69 so far this year compared with 37 in the same period last year, show the latest figures from the World Health Organization. By the end of 2010, 144 new cases had been recorded compared with 32 in 2007.

Although the incidence of polio has been reduced by 99% over the past 20 years, the rising numbers of …
Human platelet Fc receptor for immunoglobulin G. Identification as a 40,000-molecular-weight membrane protein shared by monocytes.
Authors: S I Rosenfeld, R J Looney, J P Leddy, D C Phipps, G N Abraham, C L Anderson
Journal: Journal of Clinical Investigation (1985)

We have recently shown that human monocytes and U937 cells possess two molecular classes of Fc gamma receptor. One, a 72,000-mol-wt sialoglycoprotein, has high affinity for certain subclasses of human and murine monomeric IgG. The other is a 40,000-mol-wt protein (p40) with low affinity for monomeric IgG but with the capacity to bind IgG aggregates or IgG-coated particles. In the present study, a 40,000-mol-wt single chain protein, apparently identical to p40 from U937 cells, was isolated from surface-radioiodinated human platelets by affinity purification using a murine IgG2b monoclonal antibody to p40. This 40,000-mol-wt protein was not seen when control IgG2b or unrelated murine monoclonal antibodies were employed in place of anti-p40. The same 40,000-mol-wt protein was also recovered from an IgG-Sepharose affinity adsorbent, but not from ovalbumin-or myoglobin-Sepharose. The 72,000-mol-wt Fc gamma receptor of monocytes was not identified on platelets. Monoclonal anti-p40 and Fab fragments derived from this antibody blocked platelet aggregation by heat-aggregated human IgG, whereas a control murine IgG2b protein had little or no inhibitory effect at 500-1,000-fold higher concentrations. A murine IgG1 monoclonal antibody, reactive with an unrelated platelet-specific membrane antigen, did not inhibit platelet responses to aggregated IgG. Anti-p40 did not affect platelet aggregation by thrombin, collagen, or fibrinogen plus ADP. Although anti-p40 did not directly aggregate platelets in the concentrations employed, cross-linking with F(ab')2 goat anti-murine Ig induced apyrase-sensitive aggregation of anti-p40-treated platelets. This indicates that p40 possesses transmembrane linkage for platelet activation and secretion. These observations strongly suggest that this newly recognized 40,000-mol-wt platelet membrane protein serves as an Fc gamma receptor.
Microdeletion and IGF2 loss of imprinting in a cascade causing Beckwith-Wiedemann syndrome with Wilms' tumor
Authors: Dirk Prawitt, Thorsten Enklaar, Barbara Gärtner-Rupprecht, Christian Spangenberg, Ekkehart Lausch, Dirk Reutzel, Stephan Fees, Maria Korzon, Izabela Brozek, Janusz Limon, David E Housman, Jerry Pelletier, Bernhard Zabel
Journal: Nature Genetics (2005)
Access to Care in Regionalized Health Care Systems-Reply
Authors: Geoffrey M. Anderson
Journal: JAMA (1996)

In Reply.  —Dr James and colleagues are correct to point out that regionalization of tertiary care services must be considered in the context of an overall system for meeting the health care needs of a population.  Dawson report, the classic British treatise on regionalization published in 1920, advised that The general availability of medical services can only be effected by new and extended organization, distributed according to the needs of the community. 1  model of organization described in the Dawson report, and subsequently implemented in many national health care systems, called for a broad base of accessible primary care services located in the community and a coordinated process for referring and transporting patients to more centralized secondary and tertiary care facilities. 2 We agree that the centralization of cardiac surgery services that was the focus of our study is only one element of a system of regionalized care.
Learning About New Therapies: Phase 3 Clinical Studies—And Beyond
Authors: Matthew C. Riddle
Journal: Diabetes Care (2013)

All new therapeutic agents, and updated versions of older ones, must be submitted for review by regulatory agencies. While this process is complex, its goals as stated by the U.S. Food and Drug Administration (FDA) are straightforward. The main aim is to determine “whether the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks” (1). Additional concerns are the information provided in the package insert and assurance of quality and consistency of the manufacturing process. Phase 3 trials, which test the safety and efficacy of candidate drugs in moderately large cohorts of human subjects, lie at the center of the process. Properly done studies of this kind help determine whether a new product should be approved for clinical use and also provide some guidance regarding how best to use it in daily practice. However, phase 3 studies—as essential as they are to the regulatory process—have important limitations, which are the topic of this commentary.

Appearing in this issue of Diabetes Care is a good example of such a study. Gough et al. (2) report a comparison of a 200 units/mL (U200) formulation of degludec, a long-acting insulin analog, with U100 insulin glargine (Lantus). The study was well designed and well conducted. The investigators enrolled 457 participants with type 2 diabetes no longer well controlled with oral therapies alone (mean A1C ∼8.2%), and randomized them to begin and titrate dosage of once-daily U200 degludec or U100 glargine using a typical treat-to-target scheme for 26 weeks. Efficacy of the new agent was assessed by the reduction of A1C from baseline, and its safety by, among other measurements, the frequency of hypoglycemic events. As in many studies, the main end point was noninferiority of glycemic improvement versus a well-known active comparator. The results …
Cell-mediated immunity in Darier's disease: effect of systemic retinoid therapy
Authors: ANNE-MARIA SOPPI, ESA SOPPI, JUSSI ESKOLA, CHRISTER T. JANSEN
Journal: British Journal of Dermatology (1982)

In five patients with Darier's disease, lymphocyte subpopulations, lymphocyte responsiveness to phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and purified protein derivative of tuberculin (PPD), leukocyte migration inhibitory factor (LMIF) production and suppressor cell activities were studied before and during oral etretinate treatment. Pre‐therapy investigations of cell‐mediated immunity showed no severe immunological dysfunction, although high responses to supra‐optimal Con A concentrations suggested abnormalities in immunoregulatory lymphocyte subpopulations. In addition, two patients showed enhanced LMIF production upon stimulation with Con A, PWM and PPD. Retinoid therapy decreased the number of peripheral blood total leukocytes, lymphocytes and T‐cells, normalized the LMIF production, and decreased the lymphocyte responses to mitogens. Furthermore, the dose‐response curve to Con A changed toward normal and the suppressor cell activity regulating Con A responses tended to increase.
Blindness and Quinin.
Authors: J. F. Baldwin
Journal: JAMA (1897)

Columbus, Ohio, Feb. 2, 1897. <h3>To the Editor:</h3> —In your issue of Nov. 7, 1896, Dr. H. B. Ellis, of Los Angeles, Cal., reports a case of total blindness, "possibly due to an overdose of quinin." I have read his report with interest, although I can not but regard the quinin as a very improbable factor in the production of the blindness. The report, however, reminds me of a case which occurred many years ago in the practice of my preceptor, Dr. J. C. Reeve, of Dayton, Ohio. A young man came to the office complaining of symptoms which lead to a diagnosis of malaria. A prescription, containing quinin as the chief ingredient, was given him. A few hours later he reported that he had become suddenly and entirely deaf. This deafness was absolute and permanent. He had, however, not taken a single dose of his medicine. Had he taken
Detection of Renal Artery Stenosis by Means of Captopril Renal Scintigraphy in Patients with Multiple Renal Arteries
Authors: STEFANO FANTI, MAURIZIO DONDI, LIBERO BAROZZI, MAURIZIO LEVORATO, NINO MONETTI
Journal: Clinical Nuclear Medicine (1992)

Both captopril renal scintigraphy (CRS) and conventional arteriography were retrospectively evaluated in 64 patients to study CRS efficacy in hypertensive patients with multiple renal arteries (MRA). The presence of MRA was angiographically demonstrated in 9 patients, 7 unilaterally and 2 bilaterally, with a total of 11 kidneys supplied by 2 or more arteries. Overall, 25 MRA were identified and 7 were affected by stenosis of >50%, causing a reduction of arterial supply in 5 of 11 kidneys. CRS correctly diagnosed all five ischemic kidneys (true positives) and five of six nonischemic kidneys (true negatives); in one case in which perfusion was not reduced, the CRS diagnosis was falsely positive. In the presence of MRA, CRS proved effective in identifying renal artery stenosis of >50%, involving either one or all the MRA. This study shows that the presence of MRA is not a drawback in the evaluation of renal artery stenosis by means of CRS.
Conceptualizing Physician Professionalism
Authors: Andrew Fesnak
Journal: JAMA (2011)

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Charles Lasègue and His 'Considerations on Sciatica'
Authors: Oscar Sugar
Journal: JAMA (1985)

The eponym Lasègue sign has been applied to the increase in sciatic pain caused by flexing the extended lower extremity on the abdomen. The sign was never put into writing by Lasègue but by his pupils. He did not describe the test in the usual reference, "Considerations on Sciatica," in 1864. That article has to do with his analysis of then-current theories of sciatica and his own clinical observations. Sciatica was divided into a benign and a serious form, and two examples of each were described. Emphasis was laid on the constant, fixed sciatic pain, as contrasted with the irregular, largely nocturnal, episodes of lancinating pain. Atrophy of leg muscles was not to be explained on the basis of disuse but by a disorder of the nerve, which also was responsible for the typical neuralgia, unlike that of any other part of the body except possibly neuralgia of the brachial plexus. Treatments currently available (cupping, vesicants, and injections of atropine solution) were unavailing. The steps are unknown by which Lasègue came to modify his 1864 views that any sort of flexion or extension of the lower extremity did not exacerbate the pain; in the 1881 thesis of his pupil, Forst, that straight-leg raising sign is described and illustrated and ascribed to his teacher, Professor Lasègue.
Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology
Authors: Robert A. Rissman, Wayne W. Poon, Mathew Blurton-Jones, Salvatore Oddo, Reidun Torp, Michael P. Vitek, Frank M. LaFerla, Troy T. Rohn, Carl W. Cotman
Journal: Journal of Clinical Investigation (2004)

Neurofibrillary tangles (NFTs) are composed of abnormal aggregates of the cytoskeletal protein tau. Together with amyloid β (Aβ) plaques and neuronal and synaptic loss, NFTs constitute the primary pathological hallmarks of Alzheimer disease (AD). Recent evidence also suggests that caspases are activated early in the progression of AD and may play a role in neuronal loss and NFT pathology. Here we demonstrate that tau is cleaved at D421 (ΔTau) by executioner caspases. Following caspase-cleavage, ΔTau facilitates nucleation-dependent filament formation and readily adopts a conformational change recognized by the early pathological tau marker MC1. ΔTau can be phosphorylated by glycogen synthase kinase-3β and subsequently recognized by the NFT antibody PHF-1. In transgenic mice and AD brains, ΔTau associates with both early and late markers of NFTs and is correlated with cognitive decline. Additionally, ΔTau colocalizes with Aβ1–42 and is induced by Aβ1–42 in vitro. Collectively, our data imply that Aβ accumulation triggers caspase activation, leading to caspase-cleavage of tau, and that this is an early event that may precede hyperphosphorylation in the evolution of AD tangle pathology. These results suggest that therapeutics aimed at inhibiting tau caspase-cleavage may prove beneficial not only in preventing NFT formation, but also in slowing cognitive decline.
The Radiologist as a Consultant-Reply
Authors: Marc J. Homer
Journal: JAMA (1982)

<h3>In Reply.—</h3> If anyone is guilty of sidestepping the issue, I fear it is Dr Green. In my article, I asked clinicians to view the roentgenogram requisition as a consultation and provide pertinent clinical information to the radiologist to ensure optimal patient care. Dr Green must agree with my thesis, since he does not address this issue at all in his letter. It is obvious from Dr Green's last paragraph that the word<i>consultant</i>disturbs him because it conjures up issues of ego and turf rather than the issue of optimal patient care. To paraphase Dr Green, if the peculiar claim of the generalist gives him the expertise to manage the clinical workup, then I propose there is a similar peculiar claim of the imaging generalist (radiologist), which gives him the expertise to participate in the management of the imaging workup, since this is precisely his training. It is difficult
1105 BASELINE CHARACTERISTICS CAN HELP TO PREDICT HEPATIC DECOMPENSATION DURING ANTIVIRAL THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C AND ADVANCED LIVER CIRRHOSIS
Authors: G. Dultz, M. Seelhof, E. Herrmann, M.W. Welker, U. Mihm, G. Teuber, B. Kronenberger, M. von Wagner, C. Sarrazin, S. Zeuzem, W.P. Hofmann, Medizinische Klinik
Journal: Journal of Hepatology (2012)
Experimental transfection of macaca sylvanus with cloned human hepatitis B virus
Authors: Tarik Gheit, Souad Sekkat, Lucyna Cova, Michele Chevallier, Marie Anne Petit, Olivier Hantz, Mylene Lesenechal, Abdalah Benslimane, Christian Trepo, Isabelle Chemin
Journal: Journal of Hepatology (2002)