tbuckley/cabot-search huggingface dataset:
Simple Tests Are Often Best
Authors: James Scott
Journal: JAMA (1982)

<h3>To the Editor.—</h3> The recent editorial "Simple Tests Are Often Best" (1981; 246:1709) was a welcome voice of reason. Many physicians believe that the diagnosis of myocardial infarction must be supported by $500 worth of enzyme studies or that an ovarian cyst cannot be scheduled for surgery without expensive imaging confirmation. The clinical diagnosis is not only not stressed, but lack of extensive technological documentation may be considered poor practice of medicine. Many physicians coming from major centers believe that the daily practice of their profession should follow research protocols backed by an inexhaustible purse. Court decisions help downgrade clinical judgment. However, high technology should not replace clinical judgment but supplement it. The respectability of clinical decisions must be reestablished by the profession if we are to control the runaway costs. This is particularly valid in the light of the news that federal and state contributions to health care will
Rocky Mountain Spotted Fever: Diagnosis
Authors: J. N. MacCormack
Journal: JAMA (1976)

<h3>To the Editor.—</h3> DeShazo et al (235:1353, 1976) have shown that<i>Rickettsia rickettsii</i>infection in monkeys can be confirmed as early as four days after onset of fever. We agree that their data warrant investigation of the monocyte culture technique as a diagnostic tool in human rickettsial disease. If the monocyte culture technique is to be successfully adapted as a useful diagnostic tool for humans with Rocky Mountain spotted fever (RMSF), a major obstacle will have to be overcome. Patients with RMSF often do not seek medical care promptly, and there are sometimes delays in the initiation of appropriate antimicrobial therapy by physicians. In a study of RMSF in the southeastern part of the United States, the mean duration of time from onset of symptoms (defined as the appearance of any one of the following: headache, fever, or skin rash) to the initiation of effective treatment (tetracycline or chloramphenicol) was
Isolated Infarction of the Os Calcis in an Adult
Authors: PAUL MILNER, GEORGE BURKE
Journal: Clinical Nuclear Medicine (1993)

A 26-year-old woman with sickle cell disease and a history of multiple previous bone infarctions presented with pain and minimal soft tissue swelling of the heel; radiographs showed no bone abnormality. The HDP bone scan was positive, confirming the diagnosis of an isolated infarction of the os calcis.
Masking of Macrocytosis by α-Thalassemia in Blacks with Pernicious Anemia
Authors: Ralph Green, Wanda Kuhl, Robert Jacobson, Cage Johnson, Ralph Carmel, Ernest Beutler
Journal: New England Journal of Medicine (1982)

Pernicious anemia appears to be more common in blacks than was formerly recognized, but some features of the disease appear to differ in blacks and whites. For example, among blacks there is an earlier age at onset, a greater frequency of serum antibodies to intrinsic factor, and a lower frequency of parietal-cell antibodies1 2 3 than have been described for whites with the disease.4 5 6 7 Furthermore, Solanki et al.2 noted an absence of macrocytosis (mean cell volume <100 fl) in 15 of 36 black patients with pernicious anemia, and this absence was not always attributable to coexistent iron deficiency.In view of the . . .
TREATMENT OF PULMONARY TUBERCULOSIS WITH HYDRAZIDE DERIVATIVES OF ISONICOTINIC ACID
Authors: Irving J. Selikoff
Journal: JAMA (1952)

Schnitzer and his co-workers 1 have demonstrated that the hydrazide of isonicotinic acid (isoniazid) and several of its derivatives, including iproniazid and 1-iso-nicotinyl-2-glucosylhydrazine, have impressive antituberculous activity in mice and in vitro. These workers found members of the hydrazine series to be superior to previously utilized antimicrobial agents in the therapy of experimental tuberculosis of mice. Similar antituberculous activity of isoniazid was independently reported by Bernstein and associates 2 and recently by Domagk and his associates. 3   Clinical studies of the hydrazide derivatives of isonicotinic acid were initiated at Sea View Hospital on June 19,1951. These investigations were directed toward determination of toxicological and pharmacological properties of this new group of compounds in humans 4 ; large scale therapeutic studies were instituted Oct. 2, 1951. 5 Three compounds have been investigated by us to date. One, the glucosyl derivative, is no longer in use, since other compounds are clearly superior.  MATERIAL
Pulsus Paradoxus of the Airways
Authors: W. D. Riding
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The editorial entitled "Pulsus Paradoxus of the Airways" (232:1041, 1975) states that pulsus paradoxus was first named and described by Kussmaul in 1873. In fact, there is a much earlier description by Sir John Floyer.<sup>1</sup>In<i>A Treatise of the Asthma</i>, first published in 1698, he writes An intermitting Pulse depends on the Stop of the Circulation thro' the Lungs; because the Left Ventricle of the Heart, by that Stop, wants sufficient Blood to continue its constant Pulsation, and this is plain in the Asthma, where the Pulse intermits, because of the Constriction, which stops the Circulation through the Lungs. Pulsus paradoxus is a clinically detectable exaggeration of the normal condition and is probably present when inspiratory pressures fall more than 6 to 8 mm Hg.<sup>2</sup>The effect is magnified in asthma because, first, there is an extremely negative intrathoracic pressure during inspiration, and, second,
Palliative care services for children must adopt a family centred approach
Authors: L. Deeley, P. Stallard, M. Lewis, S. Lenton
Journal: BMJ (1998)

EDITOR—The child centred approach adopted in Goldman's article on the special problems of children with life limiting illnesses highlighted the specific needs of ill children that should be considered when a palliative care service is being developed.1 While we agree that this approach is an important step in the development of palliative care, we would argue that any palliative care service should adopt a family centred approach, which considers the needs …
The Role of Proaccelerin in Human Blood Coagulation. Evidence that Proaccelerin Is Converted to a Prothrombin-converting Principle by Activated Stuart Factor: With Notes on the Anticoagulant Action of Soybean Trypsin Inhibitor, Protamine Sulfate, and Hexadimethrine Bromide*
Authors: Robert T. Breckenridge, Oscar D. Ratnoff
Journal: Journal of Clinical Investigation (1965)

In his original description of a patient with parahemophilia and his studies on the nature of the defect, Owren (1) proposed that the missing factor, proaccelerin (Factor V), was converted, in the presence of calcium, into a prothrombin- converting substance ("prothrombinase," Factor VI) by the action of tissue thromboplastin.Other investigators, notably Ware and Seegers(2) in a series of studies that they summarized in 1948, concluded that proaccelerin was con- vrerted to an active substance, sometimes called "accelerin," by thrombin and that the "accelerin" so formed was an accessory factor during prothrombin conversion and was not essential to this process.The exact role of proaccelerin in human blood coagulation has not been settled with certainty.Several investigators (3-6) supported Ware and Seegers' hypothesis, but others (7-9) propose that prothrombin cannot be converted to throm- bin in the absence of proaccelerin and that proaccelerin manifests its action after activation by some clotting factor other than thrombin (10).Previous studies from this laboratory on the site of action of a circulating anticoagulant found
EFFECTS OF SPONTANEOUS DISEASE ON ORGAN WEIGHTS OF RABBITS
Authors: Wade H. Brown, Louise Pearce, Chester M. Van Allen
Journal: The Journal of Experimental Medicine (1926)

A group of 127 rabbits presenting clinical manifestations of disease of spontaneous origin was studied with a view to determining whether any relation could be detected between physical constitution as represented by organ weights and functional activity as measured by the efficiency of the reaction to disease. The results of the investigation are presented in tabular form and the values obtained are compared, by means of graphs, with corresponding values for normal rabbits. It was found that animals that were the subjects of disease showed decided changes in the weights of nearly all organs, changes which appeared to be of functional origin in that the values obtained for organ weights and coefficients of variation tended to conform, in general, with the efficiency of the reaction displayed by the various groups of animals into which the entire series was divided.
Cholesterol Metabolism in Gonadectomized Rats
Authors: RICHARD D. COLEMAN, YU MIN CHEN, ROSLYN B. ALFIN-SLATER
Journal: Circulation Research (1958)

In studies in which tissue concentrations of cholesterol and total lipids were determined in male and female rats fed a control diet containing fat, the effects of gonadectomy were much smaller than in animals fed a fat-free diet in which gonadectomy tended to reverse the sex differences observed in these lipid values. Other phases of lipid metabolism were shown to be sex-linked as well. Gonadectomy resulted in decreased synthesis of cholesterol in rat liver slices and changes in the fatty acid composition of cholesterol esters in the liver.
Regulation of the postsynaptic alpha-adrenergic receptor in rat mesenteric artery. Effects of chemical sympathectomy and epinephrine treatment.
Authors: W S Colucci, M A Gimbrone, R W Alexander
Journal: Circulation Research (1981)

Vascular smooth muscle sensitivity to catecholamine-induced contraction is increased after catecholamine depletion by chemical sympathectomy and decreased after exogenous catecholamine administration.To investigate the role of the vascular o-adrenergic receptor in these alterations, we used the a-1 selective radioligand, ( 3 H)-WB-4101, [phenoxy-3-3 H(JV)]-(2-(2,6-dimethoxyphenoxyethyl)aminomethyl-l,4-benzodioxane, to characterize the vascular postsynaptic a-adrenergic receptor in a membrane-rich particulate fraction of the rat mesenteric artery.Binding of ( 3 H)-WB-4101 was rapid, readily reversible, stereospecific, and saturable.Scatchard analysis described a single class of binding sites with a dissociation constant (Kd) of 0.76 ± 0.15 nM, and a maximal binding capacity (B max ) of 99 ± 13 fmol/mg protein.Alpha-adrenergic agonists competed for the ( 3 H)-WB-4101 binding site in the a-edrenergic potency order of (-)-epinephrine (Kd = 3.0 /IM) > (-)-norepinephrine (Kd = 8.8 /IM) > (-)-isoproterenol (Kd = 57 FIM), and the a-adrenergic antagonist phentolamine (Kd = 7.6 nM) was 1000 times more potent than the /?-adrenergic antagonist, (±)-propranolol (Kd = 7400 nM).The number and affinity of a-adrenergic binding sites were studied in hyper-and hypo-adrenergic states.In mesenteric arteries from rats treated with exogenous epinephrine for 4 days, B mal was decreased to 53 ± 10 fmol/ mg protein (n = 4, P < 0.01), whereas Kd for ( 3 H)-WB-4101 was unchanged.Conversely, in mesenteric arteries from rats depleted of catecholamines with reserpine, B mo , was unchanged (96 ± 15 fmol/mg protein), whereas Kd for ( 3 H)-WB-4101 was decreased to 0.34 ± 0.07 nM (n = 6, P < 0.01), and Kd for (-)-epinephrine was decreased to 0.40 ± 0.19 PM (n = 6, P < 0.01).The effect of reserpine treatment was time dependent, being evident within 1 hour, and reaching a maximum after 3-7 days.The effects of catecholamine depletion with 6-hydroxydopamine were similar to those of reserpine.Thus, experimentally induced hyper-and hypo-adrenergic states can result in regulation of the vascular a-adrenergic receptor through changes in either receptor number or affinity.Circ Res 48: 104-111, 1981AN ALTERATION in the sensitivity of blood vessels to catecholamines has been observed in a number of physiological and disease states including pregnancy (Altura and Altura, 1977), hypertension (Lais and Brody, 1975) and pheochromocytoma (Kuchel, 1977).Norepinephrine induces a specific desensitization to a-adrenergic agonists in rat aortic strips, in vitro (Carrier et al., 1978).Conversely, catecholamine depletion with reserpine (Burn and Rand, 1959) or 6-hydroxydopamine (Shibata et al., 1972) results in an increase in vascular sensitivity to catecholamines, in vitro.The molecular mechanism by which vascular sensitivity to a-adrenergic agonists is regulated is unknown; however, obser-
Abstract 93: CXCR4 expression in VHL-related and sporadic hemangioblastomas.
Authors: Roeliene C. Kruizinga, Wilfred F.A. den Dunnen, Elisabeth G.E. de Vries, Thera P. Links, Annemiek M.E. Walenkamp
Journal: Cancer Research (2013)

Abstract Background &amp; aim. Central nervous system hemangioblastomas are sporadically as well in patients with von Hippel-Lindau (VHL) disease. In VHL disease a germline mutation in the VHL- gene leads to a defect VHL protein. This results in enhanced transcription of vascular endothelial growth factor (VEGF)-A, chemokine receptor 4 (CXCR4) and its ligand (CXCL12). The aim of this study was to analyze whether VEGF-A, CXCR4, and CXCL12 protein expression differ between VHL-related and sporadic hemangioblastomas. Methods. Freshly frozen tissue of patients operated in the University Medical Center Groningen the Netherlands, for hemangioblastomas between 1995-2010 was retrieved. Thirtythree samples of 27 patients were available, including 11 patients diagnosed with VHL-disease. Immunohistochemical analysis of 33 hemangioblastoma specimens (4 VHL patients and 1 sporadic patient were included more than once) was performed for hematoxylin &amp; eosin, VEGF-A, CXCR4 and CXCL12 expression and compared with normal surrounding brain tissue. VEGF-A was evaluated describing morphology in relation to positive cells. A semi quantitative evaluation was performed for CXCL12; negative, positive (&amp;gt;1% positive cells) or strongly positive (&amp;gt;50 % positive cells or high intensity). CXCR4 was scored quantitatively by counting percentage of positive cells per specimen. Results. VEGF-A was equally expressed in all sporadic and VHL-related hemangioblastomas, and present in hemangioblastoma cells and endothelial cells. CXCL12 was strongly expressed in 78% of hemangioblastoma tissues and did not differ between sporadic and VHL-related hemangioblastomas. In all hemangioblastomas CXCR4 was overexpressed as compared to the normal surrounding brain tissue (found in 15 specimens). Interestingly, in sporadic hemangioblastomas the mean percentage of CXCR4 positive cells per specimen (15%) was higher as compared to VHL-related hemangioblastomas (7%, p=0.001). Conclusions. VEGF-A and CXCL12 protein expression was overexpressed in the majority of VHL-related and sporadic hemangioblastomas. This makes targeting VEGF-A a potential strategy for hemangioblastoma treatment. In addition, targeting CXCR4 could be of additional value as it was overexpressed in all hemangioblastomas, although differences in expression between sporadic and VHL related hemangioblastomas do exist. Supported by a grant from the Jan Kornelis de Cock Stichting and a UEF-JSM Talent Grant to RC Kruizinga. Citation Format: Roeliene C. Kruizinga, Wilfred F.A. den Dunnen, Elisabeth G.E. de Vries, Thera P. Links, Annemiek M.E. Walenkamp. CXCR4 expression in VHL-related and sporadic hemangioblastomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 93. doi:10.1158/1538-7445.AM2013-93
An Inexpensive Self-Retaining Safety-Pin Retractor
Authors: Leonard Braunstein, Melvin I. Shoul
Journal: New England Journal of Medicine (1960)

EXPOSURE is the key to good surgery. All surgeons have felt the need for better exposure in both operative and traumatic wounds. In major surgical procedures good visualization is achieved by means of long wounds, deep retractors and adequate assistance. Frequently, however, in small and more superficial wounds adequate retraction may be lacking, and the elusive bleeder may be hard to find. This is especially true in hand surgery, traumatic surgery and elective skin or subcutaneous excisions.In the past numerous mechanical devices have been substituted for the hand-held retractor. Commercially designed self-retaining retractors have been made for use in . . .
DETERMINATION OF POST-TRANSFUSION RBC VIABILITY
Authors: C. S. Marcus, B. A. Myhre, M. C. Angulo, S. H. Demianew, R. D. Salk, C. E. Essex
Journal: Clinical Nuclear Medicine (1984)

Methods for determining post-transfusion viability of stored autologous RBC's in normal adult volunteers were compared using the simultaneous administration of I-125-HSA, Cr-51-RBC's, and Tc-99m-RBC's labeled with BNL kits. Methods using a double label technique (a plasma label + an RBC label) were compared with single label techniques (RBC label only), and Cr-51-RBC results were compared to Tc-99m-RBC results. Post-infusion samples were drawn at 5, 7.5, 10, 12.5, 15, and 20 minutes and at 24 hours. Zero-time extrapolation calculations were compared with early time-averaged calculations to determine the 100% value. In addition, plasma levels of Cr-51 and Tc-99m were measured at all time periods. We found that (1) the double label technique and the single label extrapolation technique give identical results; (2) the early time-averaged methods are less accurate if there is significant loss of RBC's; (3) substitution of Tc-99m-RBC's for Cr-51-RBC's is acceptable at early times but at 24 hours they are not equivalent; Tc-99m-RBC survival at 24 hours needs to be multiplied by a factor of 1.2 to make it equivalent to Cr-51-RBC data; (4) plasma levels of Tc-99m are 2–3 times higher than Cr-51 levels at early times; at 24 hours plasma Tc-99m levels were half the early values (2% vs. 4%) but Cr-51 values were negligible (0.2%). We conclude that Tc-99m-RBC's may be used to assess post-transfusion RBC viability at 24 hours if one multiplies surviving fraction by a factor of 1.2. Either the double label technique or the single label extrapolation technique should be used.
Oncogenic BARD1 Isoforms Expressed in Gynecological Cancers
Authors: Lin Li, Stephan Ryser, Eva Dizin, Dietmar Pils, Michael Krainer, Charles Edward Jefford, Francesco Bertoni, Robert Zeillinger, Irmgard Irminger-Finger
Journal: Cancer Research (2007)

Abstract BARD1 is required for protein stability and tumor suppressor functions of BRCA1, which depend on the ubiquitin ligase activity of the BRCA1-BARD1 heterodimer. The NH2-terminal RING domains of both proteins act as interaction modules and form a ubiquitin ligase, which has functions in DNA repair, cell cycle checkpoint regulation, and mitosis. Interestingly, up-regulated expression of truncated BARD1 isoforms was found to be associated with poor prognosis in breast and ovarian cancers and, in a hormonally regulated fashion, in the human cytotrophoblast, a cell type with properties reminiscent of cancer cells. We therefore performed reverse transcription-PCR to determine the structure of BARD1 isoforms in cell lines derived from hormone-dependent and hormone-independent cancers. We found a specific combination of isoforms, generated by differential splicing and alternative transcription initiation, mostly lacking the BRCA1 interaction domain, in gynecologic but not hematologic cancer cell lines. To investigate the prevalence of BARD1 isoforms in tumors, we applied immunohistochemistry to ovarian cancers, using antibodies distinguishing full-length BARD1 and isoforms. Expression of NH2 terminally truncated BARD1 was correlated with advanced stage of cancer, and expression of spliced isoforms was typical for clear cell carcinoma, the ovarian cancer with worst prognosis, suggesting a role of BARD1 isoforms in cancer progression. To challenge this hypothesis, we silenced BARD1 isoforms in ovarian cancer cells that lacked wild-type BARD1 by siRNA interference, which led to a complete proliferation arrest. Thus, BARD1 isoform expression is required for cancer cell proliferation, which is compatible with the notion that BARD1 isoforms act as cancer maintenance genes. [Cancer Res 2007;67(24):11876–85]
Diagnostic Potential of Serum VEGF-D for Lymphangioleiomyomatosis
Authors: Lisa R. Young, Yoshikazu Inoue, Francis X. McCormack
Journal: New England Journal of Medicine (2008)

rate of recurrence, particularly distant recurrence, by approximately 50 percent" 1 and "The addition of trastuzumab to paclitaxel after a regimen of doxorubicin and cyclophosphamide reduced the rates of recurrence by half among women with HER2-positive breast cancer." 2 Dr. Nash's letter calls attention to the importance of understanding the difference between absolute and relative risks in analyzing the results of clinical trials.
Plasmid-Encoded Proinsulin Preserves C-Peptide While Specifically Reducing Proinsulin-Specific CD8 <sup>+</sup> T Cells in Type 1 Diabetes
Authors: Bart O. Roep, Nanette Solvason, Peter A. Gottlieb, Joana R. F. Abreu, Leonard C. Harrison, George S. Eisenbarth, Liping Yu, Michael Leviten, William A. Hagopian, John B. Buse, Matthias von Herrath, Joanne Quan, Robert S. King, William H. Robinson, Paul J. Utz, Hideki Garren, Lawrence Steinman
Journal: Science Translational Medicine (2013)

A plasmid encoding proinsulin reduces the frequency of CD8 + T cells reactive to proinsulin while preserving C-peptide.
Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis
Authors: Albert Pardo, Ramon Bartolí, Vicente Lorenzo-Zúñiga, Ramon Planas, Belén Viñado, Joan Riba, Eduard Cabré, Justiniano Santos, Teresa Luque, Vicenç Ausina, Miguel A. Gassull
Journal: Hepatology (2000)

Deranged intestinal motility, which occurs in cirrhosis, may facilitate the development of intestinal bacterial overgrowth (IBO), which can lead to bacterial translocation (BT). To assess the effect of cisapride on IBO and BT in cirrhosis, cirrhotic rats received cisapride or a placebo for 7 days, and measurements of jejunal bacterial content and BT studies were performed. In addition, jejunal fluid from 46 cirrhotic patients was obtained for quantitative bacterial culture. Those patients in whom gram-negative IBO was detected were randomized to receive or not to receive cisapride (20 mg twice per day) for 1 week. Cisapride significantly reduced IBO in cirrhotic rats. In addition, no BT was documented in treated animals, whereas it occurred in 40% in nontreated cirrhotic rats. Total IBO was documented in 23 of 46 cirrhotic patients, which was caused by gram-negative organisms in 10 cases. Orocecal transit time (OCT) significantly decreased after cisapride therapy, and was associated with the abolishment of bacterial overgrowth caused by gram-negative organisms in 4 out of 5 treated patients, whereas it persisted in nontreated cases. Cisapride administration to cirrhotic rats resulted in a reduction of the IBO, which is associated with a marked decrease in BT. On the other hand, cisapride facilitates the abolition of IBO caused by gram-negative organisms in cirrhotic patients.
Crosstalk between Aurora-A and p53: Frequent Deletion or Downregulation of Aurora-A in Tumors from p53 Null Mice
Authors: Jian-Hua Mao, Di Wu, Jesus Perez-Losada, Tao Jiang, Qian Li, Richard M. Neve, Joe W. Gray, Wei-Wen Cai, Allan Balmain
Journal: Cancer Cell (2007)
General practitioners in partnership with management.
Authors: B J Robinson
Journal: BMJ (1993)

If relevant to clinical practice these in vitro observations suggest that pseudoallergic drug reactions may be regulated not by pharmacological specificity but by relatively non-specific protein binding properties.The displacement properties of acidic or basic protein binding drugs and effects of released vasoactive mediators are probably additive.The adverse reactions experienced by the patient reported on may therefore be attributable to the drug regimen and not solely to dexamethasone.