tbuckley/cabot-search huggingface dataset:
Novel Therapies for Tuberculosis: Tuberculosis Control and its Discontents
Authors: Jose Luis Portero, Maria Rubio
Journal: PLoS Medicine (2006)

Joal HillI read with interest the debate about for-profi t versus non-profi t institutional review boards (IRBs) [1], but was disappointed that no one addressed the ability (or inability) of for-profi t IRBs to review studies with the local context of research subjects in mind and then monitor what actually occurs during the consent process throughout the research trial.To my mind the "bigness" of for-profi t IRBs may be more of an impediment in protecting research subjects than their inherent confl ict of interest.Our IRB has reviewed consent forms approved by central/for-profi t IRBs that contained obvious errors such as schemas that did not match protocol narrative and use of eight point font in a study of geriatric subjects.Even when the initial review is outstanding, it seems a practical impossibility for a single IRB to provide meaningful monitoring of the actual consent process and implementation of the protocol at sites throughout the country.The greater "effi ciency" of for-profi t IRBs is only a meaningful benefi t if increased speed can be shown not to occur at the expense of careful review of consent forms, real understanding of the local research context, and a commitment to audit the informed consent process throughout the study for the protection of research subjects, including ongoing education and advice for researchers and their teams.This is not to say that all local IRBs perform this function as they should, but it does seem almost impossible for one IRB to perform local review and oversight for research sites around the nation in a way that really makes a difference for the men, women, and children who give of their time and their bodies so that society can benefi t.
Coronary vasodilator reserve impairment distal to systolic coronary artery compression in dogs
Authors: J. R ROULEAU, L. ROY, J.-G DUMESNIL, G. R DAGENAIS
Journal: Cardiovascular Research (1983)

To investigate the mechanism by which muscular coronary overbridging can cause myocardial ischaemia, we studied the effect of systolic compression (SC) of the proximal left circumflex coronary artery in ten anaesthetised dogs, with both intact autoregulation and maximally dilated coronary arteries. Systolic compression was produced by a mechanical device adjusted to interrupt circumflex coronary flow only during the aortic ejection period and we measured left ventricular, aortic and distal circumflex coronary pressures, phasic coronary blood flow, regional myocardial blood flow (RMBF), myocardial oxygen consumption (MVO2), and myocardial lactate extraction (MLE). During both autoregulation and maximal coronary vasodilatation, there was a diastolic time lag after SC to restart phasic circumflex coronary blood flow (34 +/- 3 vs 31 +/- 3 ms) and to increase distal circumflex coronary pressure (69 +/- 4 vs 79 +/- 6 ms). With autoregulation, SC reduced the diastolic circumflex coronary: systolic left ventricular pressure time ratio (DPTIc:SPTI) and there were no changes in the other measured variables. During maximal coronary vasodilatation and SC, the coronary vasodilator reserve, the DPTIc:SPTI ratio and the inner:outer myocardial blood flow distribution were decreased in the territory of the left circumflex coronary artery; a linear relationship was observed between the DPTIc:SPTI and the inner:outer myocardial blood flow ratio. Systolic compression during vasodilatation also produced a reduction in myocardial oxygen consumption of the whole heart and a production of lactate in the coronary sinus. These results suggest that myocardial ischaemia with a myocardial bridge is due to the combined effects of a diastolic time lag to repressurise the coronary vascular bed, of tachycardia and of coronary vasodilatation.
Combination of two mutant alpha spectrin alleles underlies a severe spherocytic hemolytic anemia.
Authors: H Wichterle, M Hanspal, J Palek, P Jarolim
Journal: Journal of Clinical Investigation (1996)

We studied a patient with a severe spherocytic hemolytic anemia without family history of spherocytosis. Analysis of patient's erythrocyte membrane proteins revealed spectrin deficiency and a truncated alpha spectrin protein. We determined that the patient is a compound heterozygote with two mutations in alpha spectrin gene. Mutation in the paternal allele, designated alpha spectrin(PRAGUE), is a transition A to G in the penultimate position of intron 36 that leads to skipping of exon 37, frameshift, and production of the truncated alpha spectrin protein. The maternal allele, designated alpha spectrin(LEPRA), contains transition C-->T in position -99 of intron 30. This mutation enhances an alternative acceptor splice site 70 nucleotides upstream from the regular site. The alternative splicing causes a frameshift and premature termination of translation leading to a significant decrease in alpha spectrin production. The alpha(LEPRA) mutation is linked to a spectrin alphaIIa marker that was found to be associated with recessive or nondominant spectrin-deficient hereditary spherocytosis in approximately 50% of studied families. We conclude that the alpha(LEPRA) mutation combined in trans with the alpha(PRAGUE) mutation underlie the severe hemolytic anemia in the proband. We suggest that allele alpha spectrin(LEPRA) may be frequently involved in pathogenesis of recessive or nondominant spectrin-deficient hereditary spherocytosis.
Reassessing the Significance of Intimal Arteritis in Kidney Transplant Biopsy Specimens
Authors: Israel D.R. Salazar, Maribel Merino López, Jessica Chang, Philip F. Halloran
Journal: Journal of the American Society of Nephrology (2015)

Intimal arteritis (the presence of v-lesions) in kidney transplant biopsy specimens is believed to have major prognostic and diagnostic significance. We assessed the relationship of v-lesions to prognosis in 703 indication biopsy specimens and used microarray-based molecular tests to re-examine the relationship of v-lesions to rejection. v-Lesions were noted in 49 specimens (7%) and were usually mild (v1). The presence of v-lesions had no effect on graft survival compared with the absence of v-lesions. Pathologists using current conventions almost always interpreted v-lesions as reflecting T cell–mediated rejection (TCMR), either pure or mixed with antibody-mediated rejection (ABMR). The molecular scores questioned the conventional diagnoses in 29 of 49 specimens (59%), including ten that were conventional TCMR with no molecular rejection and nine that were conventional TCMR mixed with pure ABMR molecularly. The presence of tubulointerstitial inflammation (i-t) meeting TCMR criteria allowed subclassification of v-lesion specimens into 21 i-t-v-lesion specimens and 28 isolated v-lesion specimens. Molecular TCMR scores were positive in 95% of i-t-v-lesion specimens but only 21% of isolated v-lesion specimens. Molecular ABMR scores were often positive in isolated v-lesion biopsies (46%). Time of biopsy after transplantation was critical for understanding isolated v-lesions: most early isolated v-lesion specimens had no molecular rejection and were DSA negative, whereas most isolated >1 year after transplantation had positive DSA and ABMR scores. Therefore, v-lesions in indication biopsy specimens do not affect prognosis and can reflect TCMR, ABMR, or no rejection. Time after transplantation, DSA, and accompanying inflammation provide probabilistic basis for interpreting v-lesions.
Measurement of Local Cerebral Blood Flow in the Unanesthetized Rat Using a Hydrogen Clearance Method
Authors: JOSEPH L. HAINING, M. Don TURNER, RALPH M. PANTALL
Journal: Circulation Research (1968)

The hydrogen clearance method for measuring local tissue blood flow was adapted for use in the brain of the unanesthetized rat by means of a stainless steel plate screw mounted in the skull as the reference electrode instead of a calomel electrode. Blood flow was measured at 3 sites in the brains of 5 three-month-old rats over a 6-week period. Blood flow in the frontal cortex and the cerebellum for all the animals averaged 79 ± 22 (SD) and 81 ± 25 ml/min/100 g tissue, respectively. The other site, supposedly the hippocampus, exhibited a two-component clearance curve in most cases. The initial rapid component was of questionable validity; the second slow component averaged 110 ± 23 ml/min/100 g. Autopsy revealed that the hippocampal electrode was actually positioned in more than one type of tissue or proximal to an interspace. Hypoxia (Po 2 = 50 mm Hg) and hypercapnia (produced by inhalation of 10% CO 2 ) increased the clearance rates two- to four-fold. The rate of local blood flow and its variability were affected by the state of the animal; anesthesia (sodium pentobarbital) decreased the rate of blood flow as anticipated, and markedly reduced the variation in rate seen in the conscious state.
pH-independent entry and sequential endosomal sorting are major determinants of hepadnaviral infection in primary hepatocytes
Authors: Anneke Funk, Mouna Mhamdi, Heinz Hohenberg, Hans Will, Hueseyin Sirma
Journal: Hepatology (2006)

Entry and intracellular transport of hepatitis B viruses have several unusual, largely unknown aspects. In this study, we explored the mode of virus entry using the duck hepatitis B virus (DHBV) and the primary hepatocyte infection model. Upon internalization, viral particles were enriched in an endosomal compartment, as revealed by biochemical and ultrastructural analysis. Virus-containing vesicles harbored early endosome markers. Kinetic analysis revealed time-dependent partial translocation of viral DNA from endosomes into the cytosol. This was strongly reduced by inhibition of vacuolar ATPase; (vATPase) activity with bafilomycin A1 and resulted in abortive infection and prevention of cccDNA formation. Inactivation of vATPase induced accumulation and stabilization of incoming viral particles in endosomes, presumably by blocking endosomal carrier vesicle–mediated cargo transport and sorting. Although neutralization of the endomembrane organelles alone led to stabilization of incoming viral particles, it did not inhibit virus infection. In line with this, a pH-dependent ectopic virus fusion at the plasma membrane could not be artificially induced. This provided further evidence for a pH-neutral translocation mechanism. Endosomal membrane potential was required for viral infection because cotreatment of cells with monensin partially overcame the inhibitory effect of bafilomycin A1. In conclusion , hepatitis B viral infection is mediated by a novel cellular entry mechanism with features different from that of all other known viruses. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Efficacy and Safety of a 4-Factor Prothrombin Complex Concentrate in Patients on Vitamin K Antagonists Presenting With Major Bleeding
Authors: Ravi Sarode, Truman J. Milling, Majed A. Refaai, Antoinette Mangione, Astrid Schneider, Billie L. Durn, Joshua N. Goldstein
Journal: Circulation (2013)

Background— Patients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal. We performed a prospective clinical trial to compare nonactivated 4-factor prothrombin complex concentrate (4F-PCC) with plasma for urgent vitamin K antagonist reversal. Methods and Results— In this phase IIIb, multicenter, open-label, noninferiority trial, nonsurgical patients were randomized to 4F-PCC (containing coagulation factors II, VII, IX, and X and proteins C and S) or plasma. Primary analyses examined whether 4F-PCC was noninferior to plasma for the coprimary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction (≤1.3) at 0.5 hour after end of infusion. The intention-to-treat efficacy population comprised 202 patients (4F-PCC, n=98; plasma, n=104). Median (range) baseline international normalized ratio was 3.90 (1.8–20.0) for the 4F-PCC group and 3.60 (1.9–38.9) for the plasma group. Effective hemostasis was achieved in 72.4% of patients receiving 4F-PCC versus 65.4% receiving plasma, demonstrating noninferiority (difference, 7.1% [95% confidence interval, –5.8 to 19.9]). Rapid international normalized ratio reduction was achieved in 62.2% of patients receiving 4F-PCC versus 9.6% receiving plasma, demonstrating 4F-PCC superiority (difference, 52.6% [95% confidence interval, 39.4 to 65.9]). Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start ( P &lt;0.02). The safety profile (adverse events, serious adverse events, thromboembolic events, and deaths) was similar between groups; 66 of 103 (4F-PCC group) and 71 of 109 (plasma group) patients experienced ≥1 adverse event. Conclusions— 4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events, as demonstrated by clinical assessments of bleeding and laboratory measurements of international normalized ratio and factor levels. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00708435.
SLOUGHING MYOMA OF THE PUERPERAL UTERUS.
Authors: PALMER FINDLEY
Journal: JAMA (1897)

The controversy so long waged as to whether myoma uteri is a cause or an effect of sterility recalls the proverbial query—"which came first the hen or the egg." Undoubtedly in not a small percentage of cases sterility antedates the appearance of myoma, but that this is not the rule will appear in the statistics reported by Playfair and Allbutt, who found in 2,035 cases of myoma uteri collected by Schroeder, Wenkel, West, McClintock and others absolute sterility in 621 cases or about 30 per cent., a percentage fully double that of the average sterility in women. Then again we have the statistics of Wenkel and Susserot,<sup>1</sup>who reported ninety-nine cases of women with myoma uteri who gave birth to children with an average of 2.8 children to the mother or a little more than one-half the average of children to the mothers of that locality. These statistics would
Which subgroup of patients with dilated cardiomyopathy would benefit from long-term beta-blocker therapy? A histologic viewpoint
Authors: Takahisa Yamada, Masatake Fukunami, Masaharu Ohmori, Katsuomi Iwakura, Kazuaki Kumagai, Nobuhiko Kondoh, Tetsuo Minamino, Eiichiro Tsujimura, Tomofumi Nagareda, Kiyoshi Kotoh, Noritake Hoki
Journal: Journal of the American College of Cardiology (1993)
TCT-352 Angiographic Features of Atherosclerotic Superficial Femoral Artery Disease in Diabetics and Non-diabetics Presenting with Claudication
Authors: Atif Mohammad, Avantika Banerjee, Mirza Baig, Gene Pershwitz, Omar Hadidi, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2012)
An Address on Alcoholic Drinks: As Diet, as Medicines, and as Poisons
Authors: A. Carpenter
Journal: BMJ (1878)

I HAvE assumed thait the establishment of an annual oration is not for the purpose of proAlaiming some new discovery, or propounding some new theory, but rather for reviewing the evidence which has been ob- tained upon some given subject, and which has been, more or less, already submitted to the notice of the assembly to whom the oration is delivered.From such a standpoint, I propose to deal with "alcobolic drinks".
269. Integrated CD28 and 4-1BB Signals Strongly Potentiate CD8+ T Cell Mediated radication of Metastatic Prostate Cancer
Authors: Xiao-Song Zhong, Maiko Matsushita, Aurore Saudemont, Elmer Santos, Michel Sadelain
Journal: Molecular Therapy (2006)

Immune-mediated tumor eradication requires the adequate expansion, trafficking and intra-tumoral activation of tumor antigen- specific T cells. Suboptimal T cell activation results in anergy and apoptosis, thereby aborting effective tumor immunity. To avoid these pitfalls, tumor-specific T cells must be given optimal activating signals at the time of antigen priming and restimulation. It is not clear, however, what costimulatory ligands or combinations thereof are best suited to achieve tumor eradication, what activating mechanisms are redundant, antagonistic or additive, nor how to most effectively provide T cell costimulation in a clinically relevant fashion.
Venous responses to salt loading in hypertensive subjects.
Authors: A Takeshita, T Ashihara, K Yamamoto, T Imaizumi, S Hoka, N Ito, M Nakamura
Journal: Circulation (1984)

It has been previously suggested that salt loading produces structural changes of the arteries in hypertensive patients who respond to salt loading with a greater rise of blood pressure. This study examined the possibility that salt loading alters venous distensibility in hypertensive patients. Twenty-one patients with essential hypertension were placed on a low-sodium diet (70 meq) for 7 days and then were placed on a high-sodium diet (345 meq) for 7 days. Patients were arbitrarily divided into two groups based on the response of their blood pressure to salt loading: (1) those whose mean blood pressure increased by more than 10% while on the high-salt diet as compared with those on the low-salt diet (salt-responsive patients, n = 8) and (2) those whose mean blood pressure did not increase by more than 10% (salt-nonresponsive patients, n = 13). The venous pressure-volume relationship was determined in the forearm with a water-filled plethysmograph when patients were on the low- and high-salt diet. Venous pressure-volume curves were not different between salt-responsive and salt-nonresponsive patients while on the low-salt diet. High-salt intake shifted the curve toward the pressure axis for salt-responsive patients (p less than .05) but not for salt-nonresponsive patients. Phentolamine, 1 mg administered intravenously for 5 min, did not significantly alter venous pressure-volume curves for either group while on the low- or high-salt diet. These results suggest that salt loading decreased venous distensibility in salt-responsive patients, which resulted from nonadrenergic mechanisms: structural changes of the veins could perhaps be included as one of these mechanisms.
MID-REGIONAL PRO-ATRIAL NATRIURETIC PEPTIDE AND MID-REGIONAL PRO-ADRENOMEDULLIN ARE VALUABLE FOR THE EVALUATION OF PATIENTS WITH ACUTE DYSPNEA: RESULTS FROM THE PRO-BNP INVESTIGATION OF DYSPNEA IN THE EMERGENCY DEPARTMENT (PRIDE) STUDY
Authors: Ravi Shah, Hanna Gaggin, Anju Bhardwaj, James Januzzi
Journal: Journal of the American College of Cardiology (2012)
More Than You Ever Wanted to Know (But Need to Know) About Glycohemoglobin Testing
Authors: David E Goldstein, Randie R Little
Journal: Diabetes Care (1994)

In this issue of Diabetes Care, Koskinen et al. report that fetal hemoglobin levels are increased in diabetic patients (this issue, L.K. Koskinen et al., p. 828–831). The study design was a cross-sectional one with glycohemoglobin and fetal hemoglobin determinations for 930 diabetic and 258 control subjects. The authors found thatalmost 7% of the diabetic subjects had fetal hemoglobin levels &amp;gt;1% compared with only∼2% of the control subjects. Furthermore, fetal hemoglobin levels were increased moreoften in those with IDDM than in those with NIDDM.
"THE STATUS OF BLOOD TRANSFUSION"
Authors: J. Shelton Horsley
Journal: JAMA (1923)

To the Editor:  —In an editorial (The Journal, September 29, p. 114) you comment on the present status of blood transfusion. After reviewing some of the work showing the disadvantages of the citrate method of transfusion, you commend very heartily whole blood transfusion. This commendation appears to be in keeping with results of physiologic and clinical investigations, but it is difficult to understand your position with regard to direct transfusion, in which the blood is directly conveyed from the artery of the donor to the vein of the recipient. The obvious objections to blood vascular suturing in transfusion are the technical difficulties and the rather prolonged incisions necessary to expose the vessels. These objections do not obtain when a short jointed cannula, such as the Bernheim cannula, is used. In a communication in the Archives of Surgery (September, 1923, pp. 466-468) I have reported fifty-four consecutive cases, in which this
Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980-2009: an international collaborative study
Authors: Daniele Moratto, Silvia Giliani, Carmem Bonfim, Evelina Mazzolari, Alain Fischer, Hans D. Ochs, Andrew J. Cant, Adrian J. Thrasher, Morton J. Cowan, Michael H. Albert, Trudy Small, Sung-Yun Pai, Elie Haddad, Antonella Lisa, Sophie Hambleton, Mary Slatter, Marina Cavazzana-Calvo, Nizar Mahlaoui, Capucine Picard, Troy R. Torgerson, Lauri Burroughs, Adriana Koliski, Jose Zanis Neto, Fulvio Porta, Waseem Qasim, Paul Veys, Kristina Kavanau, Manfred Hönig, Ansgar Schulz, Wilhelm Friedrich, Luigi D. Notarangelo
Journal: Blood (2011)
HMPAO Scintigraphy, MRI, and CT of a Vascular Fibrous Dysplasia of the Craniofacial Bones
Authors: GARY R. CONRAD, BRUCE L. DEAN, ROBERT J. BAUMANN, JAMES E. SEABOLD
Journal: Clinical Nuclear Medicine (1991)

The authors present the case of a child with a predominantly unilateral craniofacial fibrous dysplasia and a substantial redirection of internal carotid blood flow to the dysplastic bone. The case illustrates the advantages of using multiple imaging modalities in the evaluation of this disorder. CT showed the diagnostic findings of fibrous dysplasia and demonstrated the extent of bony involvement. MRI showed the extent and vascularity of the intradiploic fibrous mass and best demonstrated the distortion of underlying cerebral structures. Tc-99m HMPAO brain scintigraphy demonstrated adequate ipsilat-eral cerebral perfusion, thereby excluding any significant cerebral “steal.”
POSSIBLE PHENOLPHTHALEIN POISONING
Authors: Waldo E. Nelson
Journal: JAMA (1933)

Occasional untoward results have been reported following the use of various proprietary laxatives that supposedly contain phenolphthalein as the active ingredient. In many instances the disturbance has been chronic in nature and has followed prolonged administration. Cleeves1reports a fatal instance in a boy, aged 10 years, apparently due to the ingestion of a proprietary laxative preparation. The following case, with central nervous involvement, is presented as possibly due to excessive ingestion of a proprietary laxative:  A white boy, aged 3 years, admitted to the Children's Hospital, Dec. 25, 1932, had been ill following a heavy meal, November 24. The physician in attendance at that time suspected that the child had tuberculosis. According to the grandmother, the child was not acutely ill at this time and was not confined to bed. November 29, he chewed and swallowed a large number (probably nineteen) of gum laxative tablets. Following this, there